Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or Metastatic Cancer
Phase: PHASE1
Conditions: Neoplasms, Metastatic Cancer, Advanced Cancer, Solid Tumor, Non Small Cell Lung Cancer Metastatic, Non Small Cell Lung Cancer Stage IIIB, Non Small Cell Lung Cancer
Sponsor: Tesaro, Inc.

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 1 of 259 
 
 
 
 
 
 
NIRAPARIB; TSR-042; TSR-022  
3000-01-002 
Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based 
Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or 
Metastatic Cancer 
Sponsor: 
TESARO 
1000 Winter Street 
Suite 3300 
Waltham, MA 02451 
USA 
 
Medical Monitor: 
, MD 
Senior Medical Director 
  
Clinical Research Organization: 
Not applicable 
Sponsor Protocol No. 
3000-01-002 
IND No.: 
126472 
Study Drug Names: 
Niraparib, TSR-042, TSR-022, carboplatin-paclitaxel, 
carboplatin-pemetrexed, carboplatin–nab-paclitaxel, and 
bevacizumab 
Development Phase: 
1b 
Date of Original Protocol: 
07 July 2017 
Date of Amendment 1: 
15 November 2017 
Date of Amendment 2: 
15 August 2018 
Version of Protocol 
3.0 
 
The study will be conducted according to the protocol and in compliance with Good Clinical Practice 
(GCP), with the Declaration of Helsinki, and with other applicable regulatory requirements. 
Confidentiality Statement 
All information contained in this document is privileged and confidential to TESARO. Any 
distribution, copying, or disclosure is strictly prohibited without prior written approval by 
TESARO. 
PPD
PPD
PPD

PPD
PPD

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 3 of 259 
 
INVESTIGATOR’S AGREEMENT 
 
Declaration of the Principal Investigator 
 
Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based 
Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or 
Metastatic Cancer 
 
I have read this study protocol, including all appendices. By signing this protocol, I agree to 
conduct the clinical study, following approval by an Independent Ethics Committee/Institutional 
Review Board, in accordance with the study protocol, the current International Council for 
Harmonisation Guideline for Good Clinical Practice, and applicable regulatory requirements. 
I will ensure that all personnel involved in the study under my direction will be informed about 
the contents of this study protocol and will receive all necessary instructions for performing the 
study according to the study protocol. 
 
 
 
Principal Investigator 
 
 
 
 
Name: 
Title: 
Institution: 
 
Date 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 4 of 259 
 
1. 
SYNOPSIS 
Name of Sponsor/Company: TESARO 
Name of Investigational Products: Niraparib, TSR-042, TSR-022, carboplatin-paclitaxel, 
carboplatin-pemetrexed, carboplatin–nab-paclitaxel, bevacizumab 
Name of Active Ingredients: Niraparib, TSR-042, TSR-022, carboplatin-paclitaxel, carboplatin-
pemetrexed, carboplatin–nab-paclitaxel, bevacizumab 
Title: Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based 
Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or Metastatic 
Cancer 
Study Center(s): Up to 31 sites in the United States 
Principal Investigator: To be determined 
Investigators: To be determined 
Studied Period (Years): 
Estimated date of first patient enrolled: Q4 2017 
Estimated date of last patient enrolled: Q2 or Q3 2019 
Phase of Development: 
Phase 1b 
Objectives: 
Primary Objectives 
The primary objectives for Part A of this study are as follows: 
 
To evaluate dose-limiting toxicities (DLTs) of TSR-042 and niraparib combination 
treatment during the first cycle of treatment in patients with advanced or metastatic cancer 
and to establish a recommended Phase 2 dose (RP2D) 
 
To evaluate the safety and tolerability of TSR-042 and niraparib combination treatment 
The primary objectives for Part B of this study are as follows: 
 
To evaluate DLTs of TSR-042 and carboplatin-paclitaxel combination treatment during 
the first cycle of treatment in patients with advanced or metastatic cancer and to confirm 
an RP2D 
 
To evaluate the safety and tolerability of TSR-042 and carboplatin-paclitaxel combination 
treatment 
The primary objectives for Part C of this study are as follows: 
 
To evaluate DLTs of TSR-042, niraparib and bevacizumab combination treatment during 
the first cycle of treatment in patients with advanced or metastatic cancer and to establish 
an RP2D 
 
To evaluate the safety and tolerability of TSR-042, niraparib and bevacizumab 
combination treatment 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 5 of 259 
 
The primary objectives for Part D of this study are as follows: 
 
To evaluate DLTs of TSR-042, carboplatin-paclitaxel and bevacizumab combination 
treatment during the first cycle of treatment in patients in whom carboplatin-paclitaxel 
and bevacizumab combination treatment is a reasonable therapy, and to confirm an RP2D 
 
To evaluate the safety and tolerability of TSR-042, carboplatin-paclitaxel and 
bevacizumab combination treatment 
The primary objectives for Part E of this study are as follows: 
 
To evaluate DLTs of TSR-042 and carboplatin-pemetrexed combination treatment during 
the first cycle of treatment, as first-line treatment in patients with advanced or metastatic 
non-squamous non-small cell lung cancer (NSCLC), and to confirm an RP2D 
 
To evaluate the safety and tolerability of TSR-042 and carboplatin-pemetrexed 
combination treatment 
The primary objectives for Part F of this study are as follows: 
 
To evaluate DLTs of TSR-042, TSR-022, and carboplatin-pemetrexed combination 
treatment during the first cycle of treatment, as first-line treatment in patients with 
advanced or metastatic non-squamous NSCLC, and to confirm an RP2D 
 
To evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin-pemetrexed 
combination treatment 
The primary objectives for Part G of this study are as follows: 
 
To evaluate DLTs of TSR-042 and carboplatin–nab-paclitaxel combination treatment 
during the first cycle of treatment, as first-line treatment in patients with advanced or 
metastatic NSCLC, and to confirm an RP2D 
 
To evaluate the safety and tolerability of TSR-042 and carboplatin–nab-paclitaxel 
combination treatment 
The primary objectives for Part H of this study are as follows: 
 
To evaluate DLTs of TSR-042, TSR-022, and carboplatin–nab-paclitaxel combination 
treatment during the first cycle of treatment, as first-line treatment in patients with 
advanced or metastatic NSCLC, and to confirm an RP2D 
 
To evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin–
nab-paclitaxel combination treatment 
The primary objectives for Part I of this study are as follows: 
 
To evaluate DLTs of TSR-042, TSR-022, and carboplatin-paclitaxel combination 
treatment during the first cycle of treatment, as first-line treatment in patients with 
advanced or metastatic NSCLC, and to confirm an RP2D 
 
To evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin-paclitaxel 
combination treatment 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 6 of 259 
 
Secondary Objectives 
The secondary objectives for Part A of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including 
objective response rate (ORR), duration of response (DOR), disease control rate (DCR), 
and progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors 
version 1.1 (RECIST v1.1) 
 
To evaluate the pharmacokinetics (PK) of niraparib, its major metabolite M1, and TSR-
042 during TSR-042 and niraparib combination treatment 
 
To evaluate anti-drug antibodies (ADAs) of TSR-042 during TSR-042 and niraparib 
combination treatment  
The secondary objectives for Part B of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of TSR-042 during TSR-042 and carboplatin-paclitaxel combination 
treatment 
 
To evaluate ADAs of TSR-042 during TSR-042 and carboplatin-paclitaxel combination 
treatment 
The secondary objectives for Part C of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of niraparib, its major metabolite M1, and TSR-042 during TSR-042, 
niraparib and bevacizumab combination treatment 
 
To evaluate ADAs of TSR-042 during TSR-042, niraparib and bevacizumab combination 
treatment  
The secondary objectives for Part D of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of TSR-042 during TSR-042, carboplatin-paclitaxel and bevacizumab 
combination treatment 
 
To evaluate ADAs of TSR-042 during TSR-042, carboplatin-paclitaxel and bevacizumab 
combination treatment 
The secondary objectives for Part E of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of TSR-042 during TSR-042 and carboplatin-pemetrexed combination 
treatment 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 7 of 259 
 
 
To evaluate ADAs of TSR-042 during TSR-042 and carboplatin-pemetrexed combination 
treatment 
The secondary objectives for Part F of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment 
 
To evaluate ADAs of TSR-042 and TSR-022 during TSR-042, TSR-022, and carboplatin-
pemetrexed combination treatment 
The secondary objectives for Part G of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of TSR-042 during TSR-042 and carboplatin–nab-paclitaxel 
combination treatment 
 
To evaluate ADAs of TSR-042 during TSR-042 and carboplatin–nab-paclitaxel 
combination treatment 
The secondary objectives for Part H of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin–nab-paclitaxel  combination treatment 
 
To evaluate ADAs of TSR-042 and TSR-022 during TSR-042, TSR-022, and carboplatin–
nab-paclitaxel  combination treatment 
The secondary objectives for Part I of the study are as follows: 
 
To evaluate measures of clinical benefit as assessed by the Investigators, including ORR, 
DOR, DCR, and PFS by RECIST v1.1 
 
To evaluate the PK of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin-paclitaxel combination treatment 
 
To evaluate ADAs of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin-paclitaxel combination treatment 
Exploratory Objectives 
The exploratory objectives for Part A of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042 and niraparib 
combination treatment based on the pretreatment biomarker profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042 and niraparib combination treatment and correlate with clinical 
benefit 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 8 of 259 
 
The exploratory objectives for Part B of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042 and 
carboplatin-paclitaxel combination treatment based on the pretreatment biomarker profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042 and carboplatin-paclitaxel combination treatment and correlate with 
clinical benefit 
The exploratory objectives for Part C of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042, niraparib and 
bevacizumab combination treatment based on the pretreatment biomarker profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042, niraparib and bevacizumab combination treatment and correlate with 
clinical benefit 
The exploratory objectives for Part D of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042, 
carboplatin-paclitaxel and bevacizumab combination treatment based on the pretreatment 
biomarker profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042, carboplatin-paclitaxel and bevacizumab combination treatment and 
correlate with clinical benefit 
The exploratory objectives for Part E of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042 and carboplatin-
pemetrexed combination treatment based on the pretreatment biomarker profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042 and carboplatin-pemetrexed combination treatment and correlate with 
clinical benefit 
The exploratory objectives for Part F of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment based on the pretreatment biomarker 
profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042, TSR-022, and carboplatin-pemetrexed treatment and correlate with 
clinical benefit 
The exploratory objectives for Part G of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042 and carboplatin–
nab-paclitaxel  combination treatment based on the pretreatment biomarker profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042 and carboplatin–nab-paclitaxel  combination treatment and correlate 
with clinical benefit 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 9 of 259 
 
The exploratory objectives for Part H of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042, TSR-022, and 
carboplatin–nab-paclitaxel  combination treatment based on the pretreatment biomarker 
profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042, TSR-022, and carboplatin–nab-paclitaxel  treatment and correlate 
with clinical benefit 
The exploratory objectives for Part I of the study are as follows: 
 
To explore biomarkers that may be predictive of benefit from TSR-042, TSR-022, and 
carboplatin-paclitaxel combination treatment based on the pretreatment biomarker profile 
 
To explore changes in biomarkers (e.g., immune cells and immune proteins) in the blood 
following TSR-042, TSR-022, and carboplatin-paclitaxel treatment and correlate with 
clinical benefit 
Methodology: 
Overall Study Design 
This is a multicenter, open-label, 9-part Phase 1b study evaluating the safety and preliminary efficacy 
of niraparib or niraparib/bevacizumab in combination with TSR-042 treatment and confirming the 
safety and tolerability of carboplatin-paclitaxel, carboplatin-paclitaxel/bevacizumab, carboplatin-
pemetrexed, TSR-022/carboplatin-pemetrexed, carboplatin–nab-paclitaxel, TSR-022/carboplatin–
nab-paclitaxel, and TSR-022/carboplatin-paclitaxel in combination with TSR-042 treatment in 
patients with advanced or metastatic cancer. Specifically, patients eligible for this study are as follows: 
 
Part A (dose finding—TSR-042 and niraparib combination treatment): all comers, defined 
as patients with previously treated advanced or metastatic cancer  
 
Part B (safety and tolerability evaluation—TSR-042 and carboplatin-paclitaxel 
combination treatment): patients with advanced or metastatic cancer for which treatment 
with carboplatin and paclitaxel is indicated (e.g., including, but not limited to, non-small 
cell lung cancer [NSCLC], ovarian cancer, and cervical cancer) 
 
Part C (dose finding—TSR-042, niraparib and bevacizumab combination treatment): all 
comers, defined as patients with previously treated advanced or metastatic cancer  
 
Part D (safety and tolerability evaluation—TSR-042, carboplatin-paclitaxel and 
bevacizumab combination treatment): in patients in whom carboplatin-paclitaxel and 
bevacizumab is considered a reasonable therapy 
 
Part E (safety and tolerability evaluation—TSR-042 and carboplatin-pemetrexed 
combination treatment): as first-line treatment in patients with advanced or metastatic 
non-squamous NSCLC 
 
Part F (safety and tolerability evaluation—TSR-042, TSR-022, and carboplatin-
pemetrexed combination treatment): as first-line treatment in patients with advanced or 
metastatic non-squamous NSCLC 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 10 of 259 
 
 
Part G (safety and tolerability evaluation—TSR-042 and carboplatin–nab-paclitaxel  
combination treatment): as first-line treatment in patients with advanced or metastatic 
NSCLC 
 
Part H (safety and tolerability evaluation—TSR-042, TSR-022, and carboplatin–
nab-paclitaxel  combination treatment): as first-line treatment in patients with advanced or 
metastatic NSCLC 
 
Part I (safety and tolerability evaluation—TSR-042, TSR-022, and carboplatin-paclitaxel 
combination treatment): as first-line treatment in patients with advanced or metastatic 
NSCLC 
The study will include 9 parts: Parts A, B, C, D, E, F, G, H, and I. Part A will be a dose-finding 
evaluation conducted in all comers (12 to 24 patients) to determine the RP2D of niraparib in 
combination with TSR-042. Part B will evaluate the safety and tolerability of TSR-042 and 
carboplatin-paclitaxel combination treatment in approximately 12 patients with advanced or metastatic 
cancer for which carboplatin-paclitaxel is indicated. Part C will be a dose-finding evaluation 
conducted in all comers (6 to 24 patients) to determine the RP2D of niraparib and bevacizumab in 
combination with TSR-042. Part D will evaluate the safety and tolerability of TSR-042, carboplatin-
paclitaxel and bevacizumab combination treatment in 6 to 12 patients in whom carboplatin-paclitaxel 
and bevacizumab combination treatment is considered a reasonable therapy. Part E will evaluate the 
safety and tolerability of TSR-042 and carboplatin-pemetrexed combination treatment as first-line 
treatment in 6 to 12 patients with advanced or metastatic non-squamous NSCLC. Part F will evaluate 
the safety and tolerability of TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment 
as first-line treatment in 6 to 24 patients with advanced or metastatic non-squamous NSCLC. Part G 
will evaluate the safety and tolerability of TSR-042 and carboplatin–nab-paclitaxel combination 
treatment as first-line treatment in 6 to 12 patients with advanced or metastatic NSCLC. Part H will 
evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin–nab-paclitaxel combination 
treatment as first-line treatment in 6 to 24 patients with advanced or metastatic NSCLC. Part I will 
evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin-paclitaxel combination 
treatment as first-line treatment in 6 to 24 patients with advanced or metastatic NSCLC. 
Enrollment of patients into Parts A, B, D, E, G, and I will occur concurrently. Part C will be initiated 
after dose level 1 (niraparib 200 mg) in Part A is determined to be safe. Part F will be initiated after 
TSR-042 and carboplatin-pemetrexed combination treatment in Part E is determined to be safe. Part H 
will be initiated after TSR-042 and carboplatin–nab-paclitaxel combination treatment in Part G is 
determined to be safe. 
The study will be conducted in conformance with the protocol, Good Clinical Practice (GCP), and 
applicable regulatory requirements. The study design is provided below. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 11 of 259 
 
Study Design 
 
 
 
 
 
 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 12 of 259 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = adverse event; AUC = area under the plasma or serum concentration-time curve; D1 = Day 
1; D21 = Day 21; DLT = dose-limiting toxicity; N = xx; PK = pharmacokinetics; Q1W = every week; 
Q3W = every 3 weeks; Q6W = every 6 weeks; QD = once daily; RP2D = recommended Phase 2 dose. 
a In addition to receiving niraparib (Part A), carboplatin-paclitaxel (Part B), niraparib and bevacizumab (Part C), 
carboplatin-paclitaxel and bevacizumab (Part D), carboplatin-pemetrexed (Part E), TSR-022 and carboplatin-
pemetrexed (Part F), carboplatin–nab-paclitaxel (Part G), TSR-022 and carboplatin–nab-paclitaxel (Part H), 
and TSR-022 and carboplatin-paclitaxel (Part I) at the specified regimen, all patients will be administered 
TSR-042 at 500 mg on Day 1 of every cycle (Q3W) for 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 
will be administered to patients in Parts A, B, C, and D at 1,000 mg on Day 1 of every other cycle (Q6W) until 
the patient discontinues study treatment. Patients in Parts E, F, G, H, and I will continue to receive TSR-042 
500 mg on Day 1 of every cycle (Q3W) throughout the study. 
b The RP2D for TSR-042 and niraparib combination treatment (Part A); TSR-042 and carboplatin-paclitaxel 
combination treatment (Part B); TSR-042, niraparib, and bevacizumab combination treatment (Part C); 
TSR-042, carboplatin-paclitaxel, and bevacizumab combination treatment (Part D); TSR-042 and carboplatin-
pemetrexed (Part E); TSR-042, TSR-022, and carboplatin-pemetrexed (Part F); TSR-042 and carboplatin–
nab-paclitaxel (Part G); TSR-042, TSR-022, and carboplatin–nab-paclitaxel (Part H); and TSR-042, TSR-022, 
and carboplatin-paclitaxel (Part I), will be determined or confirmed based on an evaluation of multiple 
endpoints, which may include the DLT rate in first and subsequent cycles of combination treatment, the rate of 
dose modifications for non-DLT AEs, the ability to manage toxicities, PK, niraparib dose intensity, and signs 
of clinical efficacy. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 13 of 259 
 
c 12 to 24 patients will be enrolled in Part A to determine the RP2D for TSR-042 and niraparib combination 
treatment.  
d Initially, dose level 1 in Part C will enroll 6 to 12 patients to determine the RP2D for TSR-042, niraparib, and 
bevacizumab combination treatment. Dose level 2 is optional. 
e  900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 (300 mg) if needed. Based on 
available safety information, the Sponsor may decide to test additional dose levels. 
General Study Conduct 
Part A: Dose Finding for TSR-042 and Niraparib Combination Treatment  
Determination of the RP2D for TSR-042 and niraparib combination treatment will be conducted using 
the dose levels described in the table below: 
 
Dose Regimen for TSR-042 and Niraparib Combination Treatment 
Dose Level 
Niraparib 
TSR-042 Dose 
1 
200 mg administered on Days 1 to 21 repeated Q3W 
500 mg on Day 1 of every cycle 
(Q3W) for 4 cycles, followed by 
1,000 mg on Day 1 of every 
other cycle (Q6W) beginning on 
Day 1/Cycle 5  
2 
300 mg administered on Days 1 to 21 repeated Q3W 
Abbreviations: Q3W = every 3 weeks; Q6W = every 6 weeks. 
 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤1 patient experiences a 
DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 patients experience 
DLTs, 6 additional patients will be enrolled at dose level 1. If 12 patients are enrolled at dose level 1 
and ≤3 of 12 patients experience DLTs, dose level 1 will be considered safe. The combination therapy 
will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see Part A 
dose-finding scheme below). However, when determining the RP2D, the Sponsor will review and 
consider safety data from all patients treated with the combination therapy. Note: Part A has been 
completed as of Amendment 2. 
Once dose level 1 (200 mg) is determined to be safe, the decision to open the next higher dose level 
(dose level 2) will be made based on evaluation of safety data from dose level 1. Dose level 2 
(300 mg) will be opened only if less than one-third of evaluable patients (i.e., ≤1 of 6 patients or 
≤3 of 12 patients) at dose level 1 experience a DLT during Cycle 1. Patients at dose level 2 will be 
enrolled using the same 6 + 6 scheme used at dose level 1. For patients in Part A, the dose of niraparib 
may be increased after Cycle 2 to a higher dose level that has been found to be safe during the 
dose-escalation phase following discussion with the Sponsor. No further dose escalation will be 
evaluated if dose level 2 is reached. 
The RP2D for TSR-042 and niraparib combination treatment will be a dose with DLTs observed in 
less than one-third of evaluable patients (i.e., ≤1 of 6 patients or ≤3 of 12 patients) during Cycle 1 of 
combination treatment and will be determined following discussion and agreement between the 
Investigators and Sponsor based on evaluation of multiple endpoints, which may include the DLT rate 
in first and subsequent cycles of combination treatment, the rate of dose modifications for non-DLT 
adverse events (AEs), the ability to manage toxicities, PK, niraparib dose intensity, and signs of 
clinical efficacy. The goal will be to identify the dose and regimen of niraparib with the greatest dose 
intensity that can be safely combined with the recommended dose and regimen of TSR-042. 
The Part A dose-finding scheme is summarized below. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 14 of 259 
 
Part A Dose-Finding Scheme for TSR-042 and Niraparib Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Niraparib will be administered at the specified dose level as described in the table above (Dose Regimen for 
TSR-042 and Niraparib Combination Treatment). In addition to receiving niraparib at the specified regimen, 
all patients will be administered TSR-042 at 500 mg on Day 1 of every cycle (Q3W) for 4 cycles. Beginning 
on Day 1 of Cycle 5, TSR-042 will be administered at 1,000 mg on Day 1 of every other cycle (Q6W). 
 
Treatment with niraparib must be interrupted for any treatment-related nonhematologic Common 
Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 AE. Once resolved to Grade ≤1, the 
patient may restart treatment with niraparib with a dose level reduction unless prophylaxis is 
considered feasible. If the event recurs at a similar or worse grade, treatment should be interrupted 
again and, upon resolution, a further dose reduction must be made to a lower dose level, if available, 
or niraparib dosing should be discontinued. For hematologic toxicities, dose interruption and 
modification for niraparib will be based on blood counts. Dose interruption is required for platelet 
count < 100,000/µL, neutrophil count < 1,000/μL, and hemoglobin ≤ 8 g/dL. Blood counts will be 
monitored weekly until recovery, after which, patients may restart treatment with niraparib at the same 
dose (first occurrence of thrombocytopenia with platelet count 75,000 to <100,000/µL only) or with a 
dose level reduction (subsequent occurrence of thrombocytopenia and any occurrence of platelet 
count < 75,000/µL, neutropenia, or anemia). Upon restarting niraparib, blood counts will continue to 
be monitored once weekly until the AE resolved to the specified blood count levels. To ensure the 
safety of the new dose, weekly blood draws for complete blood count (CBC) will be required for an 
additional 4 weeks after the AE has resolved, after which monitoring every 4 weeks may resume. 
Permanent discontinuation of niraparib is required for any confirmed diagnosis of myelodysplastic 
syndrome (MDS)/acute myeloid leukemia (AML). 
For both nonhematologic and hematologic toxicities, if the toxicity requiring dose interruption has not 
resolved to the specified level during a maximum 4-week (≤28-day) dose interruption period, the 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 15 of 259 
 
patient has already undergone a maximum of 2 dose reductions (to a minimum dose of 100 mg once 
daily [QD], or both), the patient must permanently discontinue treatment with niraparib. Once the dose 
of niraparib has been reduced, any re-escalation must be discussed with the Sponsor.  
Part B: Safety and Tolerability Evaluation for TSR-042 and Carboplatin-Paclitaxel 
Combination Treatment 
Confirmation of the RP2D for TSR-042 and carboplatin-paclitaxel combination treatment will be 
conducted using the dose level described in the table below: 
 
Dose Regimen for TSR-042 and Carboplatin-Paclitaxel Combination Treatment 
Dose Level 
Carboplatin-Paclitaxel Dose 
TSR-042 Dose 
1 
Carboplatina AUC of 5 or 6 on Day 1 Q3W and 
paclitaxel 175 mg/m2 on Day 1 Q3W 
administered for 4 to 6 cycles as clinically 
indicated 
500 mg on Day 1 of every cycle (Q3W) 
for 4 cycles, followed by 1,000 mg on 
Day 1 of every other cycle (Q6W) 
beginning on Day 1/Cycle 5  
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks; 
Q6W = every 6 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. 
 
A cohort of approximately 12 patients will be enrolled at dose level 1 in Part B. After all patients who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤3 patients experience a 
DLT (see DLT Assessment below), TSR-042 and carboplatin-paclitaxel combination treatment will be 
considered safe. The combination therapy will be considered unsafe if ≥4 of 12 patients experience 
DLTs during Cycle 1 (see Part B dose confirmation scheme below). However, when determining the 
RP2D, the Sponsor will review and consider safety data from all patients treated with the combination 
therapy. Note: Part B has been completed as of Amendment 2. 
The RP2D for TSR-042 and carboplatin-paclitaxel combination treatment will be confirmed following 
discussion and agreement between the Investigators and Sponsor based on evaluation of multiple 
endpoints, which may include the DLT rate in first and subsequent cycles of combination treatment, 
the rate of dose modifications for non-DLT AEs, the ability to manage toxicities, PK, and signs of 
clinical efficacy. 
The Part B dose confirmation scheme is summarized below. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 16 of 259 
 
Part B Dose Confirmation Scheme for TSR-042 and Carboplatin-Paclitaxel Combination 
Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Carboplatin-paclitaxel will be administered at the specified dose level as described in the table above (Dose 
Regimen for TSR-042 and Carboplatin-Paclitaxel Combination Treatment). In addition to receiving 
carboplatin-paclitaxel at the specified regimen, patients will be administered TSR-042 at 500 mg on Day 1 of 
every cycle (Q3W) for 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 will be administered at 1,000 mg on 
Day 1 of every other cycle (Q6W). 
 
Part C: Dose Finding for TSR-042, Niraparib and Bevacizumab Combination Treatment  
Determination of the RP2D for TSR-042, niraparib, and bevacizumab combination treatment will be 
conducted using the dose levels described in the table below: 
 
Dose Regimen for TSR-042, Niraparib, and Bevacizumab Combination Treatment 
Dose Level 
Niraparib Dose 
TSR-042 Dose 
Bevacizumab Dose 
1 
200 mg administered 
on Days 1 to 21 
repeated Q3W 
500 mg on Day 1 of every cycle 
(Q3W) for 4 cycles, followed by 
1,000 mg on Day 1 of every other 
cycle (Q6W) beginning on 
Day 1/Cycle 5  
15 mg/kg on Day 1 of every 
21-day cycle Q3W for up to 
15 months 
2 (optional) 
300 mg administered 
on Days 1 to 21 
repeated Q3W 
Abbreviations: Q3W = every 3 weeks; Q6W = every 6 weeks. 
 
At dose level 1 (200 mg), a cohort of 6 patients will be enrolled initially. After all patients in dose 
level 1 who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤1 patient 
experiences a DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 
patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If 12 patients are 
enrolled at dose level 1 and ≤3 of 12 patients experience DLTs, dose level 1 will be considered safe. 
The combination therapy will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs 
during Cycle 1 (see Part C dose-finding scheme below). However, when determining the RP2D, the 
Sponsor will review and consider safety data from all patients treated with the combination therapy.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 17 of 259 
 
For patients in Part C, the dose of niraparib may be increased after Cycle 2 to a higher dose level that 
has been found to be safe during the dose-escalation phase following discussion with the Sponsor. No 
further dose escalation will be evaluated if dose level 2 is reached.   
The decision to open dose level 2 (300 mg) will be made by the Sponsor based on evaluation of safety 
data from dose level 1. Dose level 2 will be optional and opened only if less than one-third of 
evaluable patients (i.e., ≤1 of 6 patients or ≤3 of 12 patients) at dose level 1 experience a DLT during 
Cycle 1. 
 
Part C Dose-Finding Scheme for TSR-042, Niraparib, and Bevacizumab Combination 
Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Niraparib and bevacizumab will be administered at the specified dose level as described in the table above 
(Dose Regimen for TSR-042, Niraparib, and Bevacizumab Combination Treatment). In addition to receiving 
niraparib at the specified regimen, all patients will be administered TSR-042 at 500 mg on Day 1 of every 
cycle (Q3W) for 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 will be administered at 1,000 mg on 
Day 1 of every other cycle (Q6W). Bevacizumab 15 mg/kg will be administered on Day 1 Q3W for up to 15 
months. 
 
Refer to the niraparib dose interruption and modification guidance described in Part A.  
 
Part D: Safety and Tolerability Evaluation for TSR-042, Carboplatin-Paclitaxel, and 
Bevacizumab Combination Treatment 
Confirmation of the RP2D for TSR-042, carboplatin-paclitaxel, and bevacizumab combination 
treatment will be conducted using the dose level described in the table below: 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 18 of 259 
 
 
Dose Regimen for TSR-042, Carboplatin-Paclitaxel, and Bevacizumab Combination Treatment 
Dose 
Level 
Carboplatin-Paclitaxel Dose 
TSR-042 Dose 
Bevacizumab Dose 
1 
Carboplatina AUC of 5 or 6 on Day 
1 Q3W and paclitaxel 175 mg/m2 on 
Day 1 Q3W administered for 4 to 6 
cycles as clinically indicated 
500 mg on Day 1 of every 
cycle (Q3W) for 4 cycles, 
followed by 1,000 mg on 
Day 1 of every other cycle 
(Q6W) beginning on Day 
1/Cycle 5  
15 mg/kg on Day 1 of 
every 21-day cycle 
Q3W for up to 15 
months 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks; 
Q6W = every 6 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. 
 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤1 patient experiences a 
DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 patients experience 
DLTs, 6 additional patients will be enrolled at dose level 1. If ≤3 of 12 patients experience DLTs at 
dose level 1, the combination will be considered safe. The combination therapy will be considered 
unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see Part D dose confirmation 
scheme below). However, when determining the RP2D, the Sponsor will review and consider safety 
data from all patients treated with the combination therapy. Note: Part D has been completed as of 
Amendment 2. 
The RP2D for TSR-042, carboplatin-paclitaxel, and bevacizumab combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles of 
combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
The Part D dose confirmation scheme is summarized below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 19 of 259 
 
Part D Dose Confirmation Scheme for TSR-042, Carboplatin-Paclitaxel, and Bevacizumab 
Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Carboplatin-paclitaxel and bevacizumab will be administered at the specified dose level as described in the 
table above (Dose Regimen for TSR-042, Carboplatin-Paclitaxel, and Bevacizumab Combination Treatment). 
In addition to receiving carboplatin-paclitaxel and bevacizumab at the specified regimen, patients will be 
administered TSR-042 at 500 mg on Day 1 of every cycle (Q3W) for 4 cycles. Beginning on Day 1 of Cycle 5, 
TSR-042 will be administered at 1,000 mg on Day 1 of every other cycle (Q6W). Bevacizumab 15 mg/kg will 
be administered on Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
 
Part E: Safety and Tolerability Evaluation for TSR-042 and Carboplatin-Pemetrexed 
Combination Treatment 
Confirmation of the RP2D for TSR-042 and carboplatin-pemetrexed combination treatment will be 
conducted using the dose level described in the table below: 
Dose Regimen for TSR-042 and Carboplatin-Pemetrexed Combination Treatment 
Dose Level 
TSR-042 Dose 
Pemetrexed Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of every 
cycle Q3W 
500 mg/m2 on Day 1 Q3W 
(with vitamin 
supplementation)  
AUC of 5 or 6 on Day 1 
Q3W administered for 4 to 6 
cycles as clinically indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a 
DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 patients experience 
DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 patients experience DLTs at 
dose level 1, the combination will be considered safe. The combination therapy will be considered 
unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see Part E dose confirmation 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 20 of 259 
 
scheme below). However, when determining the RP2D, the Sponsor will review and consider safety 
data from all patients treated with the combination therapy.  
The RP2D for TSR-042 and carboplatin-pemetrexed combination treatment will be confirmed 
following discussion and agreement between the Investigators and Sponsor based on evaluation of 
multiple endpoints, which may include the DLT rate in first and subsequent cycles of combination 
treatment, the rate of dose modifications for non-DLT AEs, the ability to manage toxicities, PK, and 
signs of clinical efficacy. 
The Part E dose confirmation scheme is summarized below. 
Part E Dose Confirmation Scheme for TSR-042 and Carboplatin-Pemetrexed Combination 
Treatment 
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatin-pemetrexed will be administered at the specified dose level as described in the table above (Dose 
Regimen for TSR-042 and carboplatin-pemetrexed combination treatment). In addition to receiving 
carboplatin-pemetrexed at the specified regimen, patients will be administered TSR-042 at 500 mg on Day 1 
of every cycle Q3W.  
Part F: Safety and Tolerability Evaluation for TSR-042, TSR-022, and Carboplatin-Pemetrexed 
Combination Treatment  
Part F will begin after combination therapy in Part E has been determined as safe. Confirmation of the 
RP2D for TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment will be conducted 
using the dose levels described in the table below: 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 21 of 259 
 
 
Dose Regimen for TSR-042, TSR-022, and Carboplatin-Pemetrexed Combination Treatment 
Dose 
Level 
TSR-042 Dose 
TSR-022 Dose 
Pemetrexed Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of 
every cycle Q3W 
900 mg on Day 1 
Q3Wb 
500 mg/m2 on Day 1 
Q3W (with vitamin 
supplementation)  
AUC of 5 or 6 on 
Day 1 Q3W 
administered for 4 to 
6 cycles as clinically 
indicated 
-1 
500 mg on Day 1 of 
every cycle Q3W 
300 mg on Day 1 
Q3Wb 
500 mg/m2 Day 1 
Q3W (with vitamin 
supplementation)  
AUC of 5 or 6 on 
Day 1 Q3W 
administered for 4 to 
6 cycles as clinically 
indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. 
b 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available 
safety information, the Sponsor may decide to test additional dose levels of TSR-022. 
 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a 
DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 patients experience 
DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 patients experience DLTs, 
dose level 1 will be considered safe. If ≥ 4 of 12 patients experience DLTs at dose level 1, dose 
level -1 will enroll 6 patients. After all patients in dose level -1 who are evaluable for safety have 
completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a DLT, dose level -1 will be 
considered safe. If 2 of 6 patients experience DLTs, 6 additional patients will be enrolled at dose 
level -1. If ≤ 3 of 12 patients experience DLTs, dose level -1 will be considered safe. The combination 
therapy at dose level -1 will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs 
during Cycle 1 (see Part F dose confirmation scheme below). However, when determining the RP2D, 
the Sponsor will review and consider safety data from all patients treated with the combination 
therapy.  
The RP2D for TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles of 
combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
The Part F dose confirmation scheme is summarized below. 
 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 22 of 259 
 
Part F Dose Confirmation Scheme for TSR-042, TSR-022, and Carboplatin-Pemetrexed 
Combination Treatment  
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatin-pemetrexed will be administered at the specified dose level as described in the table above (Dose 
Regimen for TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment). In addition to receiving 
carboplatin-pemetrexed at the specified regimen, patients will be administered TSR-042 at 500 mg on Day 1 
of every cycle Q3W and TSR-022 at 900 mg on Day1 Q3W.  
b Patients at dose level -1 will be enrolled using the same 6 + 6 scheme used at dose level 1. 
 
Part G: Safety and Tolerability Evaluation for TSR-042 and Carboplatin–Nab-paclitaxel 
Combination Treatment 
Confirmation of the RP2D for TSR-042 and carboplatin–nab-paclitaxel combination treatment will be 
conducted using the dose level described in the table below: 
Dose Regimen for TSR-042 and Carboplatin–Nab-Paclitaxel Combination Treatment 
Dose Level 
TSR-042 Dose 
Nab-Paclitaxel Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of every 
cycle Q3W 
100 mg/m2 on Days 1, 8, and 
15 (Q1W) of every 3-week 
cycle, administered for 4 to 6 
cycles as clinically indicated 
AUC of 5 or 6 on Day 1 
Q3W administered for 4 to 6 
cycles as clinically indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q1W = every week; 
Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 23 of 259 
 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a 
DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 patients experience 
DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 patients experience DLTs, 
dose level 1 will be considered safe. The combination therapy will be considered unsafe if ≥3 of 6 or 
≥4 of 12 patients experience DLTs during Cycle 1 (see Part G dose confirmation scheme below). 
However, when determining the RP2D, the Sponsor will review and consider safety data from all 
patients treated with the combination therapy.  
The RP2D for TSR-042 and carboplatin–nab-paclitaxel combination treatment will be confirmed 
following discussion and agreement between the Investigators and Sponsor based on evaluation of 
multiple endpoints, which may include the DLT rate in first and subsequent cycles of combination 
treatment, the rate of dose modifications for non-DLT AEs, the ability to manage toxicities, PK, and 
signs of clinical efficacy. 
The Part G dose confirmation scheme is summarized below. 
Part G Dose Confirmation Scheme for TSR-042 and Carboplatin–Nab-Paclitaxel Combination 
Treatment 
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatinnab-paclitaxel will be administered at the specified dose level as described in the table above 
(Dose Regimen for TSR-042 and carboplatinnab-paclitaxel combination treatment). In addition to receiving 
carboplatinnab-paclitaxel at the specified regimen, patients will be administered TSR-042 at 500 mg on 
Day 1 of every cycle Q3W.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 24 of 259 
 
Part H: Safety and Tolerability Evaluation for TSR-042, TSR-022, and Carboplatin 
Nab-Paclitaxel Combination Treatment  
Part H will begin after combination therapy in Part G has been determined as safe. Confirmation of 
the RP2D for TSR-042, TSR-022, and carboplatinnab-paclitaxel combination treatment will be 
conducted using the dose levels described in the table below: 
Dose Regimen for TSR-042, TSR-022, and CarboplatinNab-Paclitaxel Combination Treatment 
Dose 
Level 
TSR-042 Dose 
TSR-022 Dose 
Nab-Paclitaxel Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of 
every cycle Q3W 
900 mg on Day 1 
Q3Wb 
100 mg/m2 on Days 1, 
8, and 15 (Q1W) of 
every 3-week cycle, 
administered for 4 to 
6 cycles as clinically 
indicated 
AUC of 5 or 6 on 
Day 1 Q3W 
administered for 
4 to 6 cycles as 
clinically indicated 
-1 
500 mg on Day 1 of 
every cycle Q3W 
300 mg on Day 1 
Q3Wb 
100 mg/m2 on Days 1, 
8, and 15 (Q1W) of 
every 3-week cycle, 
administered for 4 to 
6 cycles as clinically 
indicated 
AUC of 5 or 6 on 
Day 1 Q3W 
administered for 
4 to 6 cycles as 
clinically indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q1W = every week; 
Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. 
b 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available 
safety information, the Sponsor may decide to test additional dose levels of TSR-022. 
 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a 
DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 patients experience 
DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 patients experience DLTs, 
dose level 1 will be considered safe. If ≥ 4 of 12 patients experience DLTs at dose level 1, dose 
level -1 will enroll 6 patients. After all patients in dose level -1 who are evaluable for safety have 
completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a DLT, dose level -1 will be 
considered safe. If 2 of 6 patients experience DLTs, 6 additional patients will be enrolled at dose 
level -1. If ≤ 3 of 12 patients experience DLTs, dose level -1 will be considered safe. The combination 
therapy at dose level -1 will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs 
during Cycle 1 (see Part H dose confirmation scheme below). However, when determining the RP2D, 
the Sponsor will review and consider safety data from all patients treated with the combination 
therapy.  
The RP2D for TSR-042, TSR-022, and carboplatinnab-paclitaxel combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles of 
combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
The Part H dose confirmation scheme is summarized below. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 25 of 259 
 
Part H Dose Confirmation Scheme for TSR-042, TSR-022, and CarboplatinNab-Paclitaxel 
Combination Treatment  
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatinnab-paclitaxel will be administered at the specified dose level as described in the table above 
(Dose Regimen for TSR-042, TSR-022, and carboplatinnab-paclitaxel combination treatment). In addition to 
receiving carboplatinnab-paclitaxel at the specified regimen, patients will be administered TSR-042 at 
500 mg on Day 1 of every cycle Q3W and TSR-022 at 900 mg on Day 1 Q3W. 
b Patients at dose level -1 will be enrolled using the same 6 + 6 scheme used at dose level 1. 
Part I: Safety and Tolerability Evaluation for TSR-042, TSR-022, and Carboplatin-Paclitaxel 
Combination Treatment  
Confirmation of the RP2D for TSR-042, TSR-022, and carboplatin-paclitaxel combination treatment 
will be conducted using the dose levels described in the table below: 
Dose Regimen for TSR-042, TSR-022, and Carboplatin-Paclitaxel Combination Treatment 
Dose 
Level 
TSR-042 Dose 
TSR-022 Dose 
Carboplatin-Paclitaxel Dose 
1 
500 mg on Day 1 of 
every cycle Q3W 
900 mg on Day 1 
Q3Wb 
Carboplatina AUC of 5 or 6 on Day 1 Q3W 
and paclitaxel 175 mg/m2 on Day 1 Q3W 
administered for 4 to 6 cycles as clinically 
indicated 
-1 
500 mg on Day 1 of 
every cycle Q3W 
300 mg on Day 1 
Q3Wb 
Carboplatina AUC of 5 or 6 on Day 1 Q3W 
and paclitaxel 175 mg/m2 on Day 1 Q3W 
administered for 4 to 6 cycles as clinically 
indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 26 of 259 
 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. 
b 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available 
safety information, the Sponsor may decide to test additional dose levels of TSR-022. 
 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a 
DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 patients experience 
DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 patients experience DLTs, 
dose level 1 will be considered safe. If ≥ 4 of 12 patients experience DLTs in dose level 1, dose 
level -1 will enroll 6 patients. After all patients in dose level -1 who are evaluable for safety have 
completed Cycle 1 of combination treatment, if ≤ 1 patient experiences a DLT, dose level -1 will be 
considered safe. If 2 of 6 patients experience DLTs, 6 additional patients will be enrolled at dose 
level -1. If ≤ 3 of 12 patients experience DLTs, dose level -1 will be considered safe. The combination 
therapy at dose level -1 will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs 
during Cycle 1 (see Part I dose confirmation scheme below). However, when determining the RP2D, 
the Sponsor will review and consider safety data from all patients treated with the combination 
therapy.  
The RP2D for TSR-042, TSR-022, and carboplatin-paclitaxel combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles of 
combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
The Part I dose confirmation scheme is summarized below. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 27 of 259 
 
Part I Dose Confirmation Scheme for TSR-042, TSR-022, and Carboplatin-Paclitaxel 
Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatin-paclitaxel will be administered at the specified dose level as described in the table above (Dose 
Regimen for TSR-042, TSR-022, and carboplatin-paclitaxel combination treatment). In addition to receiving 
carboplatin-paclitaxel at the specified regimen, patients will be administered TSR-042 at 500 mg on Day 1 of 
every cycle Q3W and TSR-022 at 900 mg on Day 1 Q3W. 
b Patients at dose level -1 will be enrolled using the same 6 + 6 scheme used at dose level 1. 
 
DLT Assessment 
DLTs will be assessed during Cycle 1 (i.e., during the first 21 days of treatment on Day 1 to Day 21). 
DLT criteria are as follows: 
 
Any treatment-related Grade 4 nonhematologic clinical (nonlaboratory) AE 
 
Any treatment-related Grade 3 nonhematologic clinical (nonlaboratory) AE lasting 
>3 days despite optimal medical intervention  
 
Any treatment-related Grade 3 or 4 nonhematologic laboratory abnormality if any of the 
following also occur: 
 
The abnormality leads to hospitalization. 
 
The abnormality persists for ≥7 days from the time of AE onset and patient is 
symptomatic from the AE. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 28 of 259 
 
 
Any treatment-related hematologic toxicity defined as any of the following: 
 
Grade 4 thrombocytopenia persists for ≥7 days from the time of AE onset or Grade 3 
or 4 thrombocytopenia associated with clinically significant bleeding  
 
Grade 4 neutropenia, Grade 3 or 4 neutropenia associated with infection, or Grade 3 
or 4 febrile neutropenia persists for ≥7 days 
 
Grade 4 anemia or Grade 3 anemia requiring blood transfusion 
 
Any treatment-related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2 
 
Any treatment-related Grade 5 AE 
A patient will be considered nonevaluable for DLTs if, for any reason other than safety, the patient is 
unable to complete the 21-day combination treatment DLT observation period or is unable to take 
>80% of the intended dose of either agent. For patients who skip niraparib doses due to hematologic 
AEs based on dose modification table which do not meet the DLT criteria, it is allowed to miss up to 
10 days of niraparib during cycle 1 to be considered as evaluable for DLTs. Patients considered 
nonevaluable may be replaced after consultation between the Sponsor and Investigator. 
Niraparib administration has been safely managed with dose interruptions or adjustments for AEs, 
including laboratory abnormalities, while maintaining activity in the single-agent setting. Therefore, 
niraparib dose interruption, dose reduction, or both, for an AE that does not meet a DLT definition as 
described above will be considered a non-DLT modification for Cohorts A and C. However, patients 
requiring a non-DLT dose modification that makes them unable to take >80% of the intended dose 
during Cycle 1 will be considered nonevaluable for DLTs and will be replaced. 
Study Conduct 
All patients will begin combination treatment (TSR-042 and niraparib combination treatment for 
patients enrolled in Part A; TSR-042 and carboplatin-paclitaxel combination treatment for patients 
enrolled in Part B; TSR-042, niraparib, and bevacizumab combination treatment for patients enrolled 
in Part C; TSR-042, carboplatin-paclitaxel, and bevacizumab combination treatment for patients 
enrolled in Part D; TSR-042 and carboplatin-pemetrexed combination treatment for patients enrolled 
in Part E; TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment for patients 
enrolled in Part F; TSR-042 and carboplatin–nab-paclitaxel combination treatment for patients 
enrolled in Part G; TSR-042, TSR-022, and carboplatin–nab-paclitaxel for patients enrolled in Part H; 
and TSR-042, TSR-022, and carboplatin-paclitaxel for patients enrolled in Part I) on Day 1 of 
Cycle 1. Additional on-treatment safety assessments will be conducted on Days 8 and 15 of Cycle 1 
and on Day 1 of all subsequent cycles. Safety assessments conducted throughout the treatment period 
include symptom-directed physical examination, vital signs, electrocardiograms (ECGs), Eastern 
Cooperative Oncology Group (ECOG) performance status, and clinical laboratory assessments (CBC, 
coagulation; serum chemistry; thyroid-stimulating hormone [TSH], triiodothyronine [T3] or free 
triiodothyronine [FT3], and free thyroxine [FT4] or equivalent tests if TSH, T3 or FT3, or FT4 are not 
available; urinalysis; appropriate testing of serum tumor markers; and pregnancy testing).  
Radiographic evaluations (computed tomography [CT] or magnetic resonance imaging [MRI] of the 
chest, abdomen, and pelvis) and appropriate testing of serum tumor markers to assess the extent of 
disease will be conducted at 12 weeks after receiving the first dose of study treatment and every 
12 weeks (84 ± 10 days) thereafter until progression while on study treatment, independent of cycle 
delays or dose interruptions, or at any time when progression of disease is suspected. CT or MRI of 
the head will be conducted if clinically indicated; bone scans will be conducted per standard of care. If 
a patient discontinues treatment for a reason other than progression, death, withdrawal of consent, or 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 29 of 259 
 
loss to follow-up, radiographic scans and appropriate testing of serum tumor markers should continue 
at the specified interval.  
Per RECIST v1.1, complete response (CR) or partial response (PR) should be confirmed; tumor 
imaging for confirmation of response may be performed at the earliest 4 weeks after the first 
indication of response or at the next scheduled scan (i.e., 12 weeks later), whichever is clinically 
indicated. 
There is accumulating evidence indicating clinical benefit in a subset of patients treated with 
immunotherapy despite initial evidence of progressive disease (PD). Therefore, patients with initial 
radiologic evidence of PD who are clinically stable may continue study treatment at the Investigator’s 
discretion while awaiting confirmatory tumor imaging. Confirmatory imaging of PD is recommended 
to be performed at least 4 weeks and up to 6 weeks after initial evidence of PD. Patients with 
confirmed PD may continue study treatment at the Investigator’s discretion until the Investigator has 
determined that the patient is no longer experiencing clinical benefit or until study treatment is no 
longer tolerated by the patient. 
Blood sampling for PK, ADA, and biomarker evaluation will be conducted for patients in all parts. 
For patients in Parts F, H, and I, submission of archival formalin-fixed paraffin-embedded (FFPE) 
tumor tissue (if available) for biomarker analysis is mandatory. An optional on-treatment biopsy after 
4 to 6 weeks of treatment and an optional biopsy on progression (EOT visit) may be collected. 
Submission of FFPE tumor archival tissue samples is optional for Parts A, B, C, D, E, and G.  
For patients in Parts A, B, C, and D, blood samples for biomarker analysis will be obtained at 
screening, predose on Day 1 of Cycle 1 and Cycle 2, and at the EOT or time of disease progression. 
For patients in Parts E, F, G, H, and I, blood samples for biomarker analysis will be obtained at 
screening, predose on Day 1 and Day 15 of Cycle 1, and predose on Day 1 of Cycle 2, Cycle 4, Cycle 
6, and at the EOT or time of disease progression. 
All patients will undergo an End of Treatment visit within 7 days after study treatment discontinuation 
or at the time of disease progression, whichever occurs first. Safety follow-up visits will be conducted 
30 and 90 days (±7 days) after the last dose of study treatment. Safety follow-up visits are required 
only for those patients who have not started an alternate anticancer therapy. Thereafter, all patients 
will enter the posttreatment period for assessment of survival status and the occurrence of any new 
malignancies every 90 ± 14 days.  
All AEs will be collected and recorded for each patient from the day of signing the informed consent 
form until 30 days after last dose of study treatment; serious adverse events (SAEs) and adverse 
events of special interest (AESIs) are required to be captured through 90 days after the last dose of 
study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer 
therapy). Any event of MDS/AML or secondary cancer (new malignancies other than MDS/AML) 
must be reported to the Sponsor as soon as the Investigator becomes aware of the diagnosis, regardless 
of when it occurs. Any pregnancies that occur within 180 days posttreatment are to be captured. All 
AEs and SAEs experienced by a patient, irrespective of the suspected causality, will be monitored 
until the AE or SAE has resolved, abnormal laboratory values have returned to baseline or 
normalized, there is a satisfactory explanation for the change(s) observed, the patient is lost to follow-
up, or the patient has died. 
Number of Patients (Planned): 
Part A: 12 to 24 patients 
Part B: approximately 12 patients  
Part C: 6 to 24 patients.  
Part D: 6 to 12 patients 
Part E: 6 to 12 patients 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 30 of 259 
 
Part F: 6 to 24 patients 
Part G: 6 to 12 patients 
Part H: 6 to 24 patients 
Part I: 6 to 24 patients 
Main Criteria for Inclusion: 
Patients will be eligible for study entry if all of the following criteria are met: 
1. Patient is male or female and at least 18 years of age.  
2. Patient has histologically or cytologically proven advanced (unresectable) or metastatic cancer 
as outlined below according to study part and disease type: 
a. Part A: Patients with previously treated advanced or metastatic cancer. Patient may have 
received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal 
treatment will not be considered a prior line of treatment. 
b. Part B: Patients with advanced or metastatic cancer for which treatment with 
carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no 
more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will 
not be considered a prior line of treatment. 
c. Part C: Patients with previously treated advanced or metastatic cancer. Patient may have 
received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal 
treatment will not be considered a prior line of treatment. 
d. Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered 
appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy 
in the metastatic setting. Hormonal treatment will not be considered a prior line of 
treatment. 
e. Parts E, F, G, H, and I: Patients who have not received prior systemic therapy, including 
targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) 
NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long 
as development of advanced or metastatic disease occurred at least 12 months after 
completion of neoadjuvant or adjuvant therapy. 
3. Patient has an ECOG performance status of 0 to 1. 
4. Patient has adequate organ function defined as follows (Note: CBC test should be obtained 
without transfusion or receipt of colony-stimulating factors in the 2 weeks before obtaining 
sample): 
a. Absolute neutrophil count ≥ 1,500/μL 
b. Platelets ≥ 100,000/μL 
c. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L 
d. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance 
of ≥ 50 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5 × 
institutional ULN  
e. Total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ 1 × ULN 
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN 
unless liver metastases are present, in which case they must be ≤ 5 × ULN 
g. International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN unless the patient is 
receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is 
within therapeutic range of intended use of anticoagulants 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 31 of 259 
 
h. Activated partial thromboplastin time ≤ 1.5 × ULN unless the patient is receiving 
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of 
anticoagulants 
5. Female patient has a negative serum pregnancy test within 72 hours prior to taking study 
treatment if of childbearing potential and agrees to abstain from activities that could result in 
pregnancy from screening through 180 days after the last dose of study treatment, or is of 
nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than 
medical reasons): 
a. ≥45 years of age and has not had menses for >1 year 
b. Patients who have been amenorrheic for <2 years without history of a hysterectomy and 
oophorectomy must have a follicle stimulating hormone value in the postmenopausal 
range upon screening evaluation. 
c. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented 
hysterectomy or oophorectomy must be confirmed with medical records of the actual 
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical 
records of the actual procedure, otherwise the patient must be willing to use effective 
contraception throughout the study, starting with the screening visit through 180 days 
after the last dose of study treatment. See the study protocol for a list of acceptable birth 
control methods. Information must be captured appropriately within the site’s source 
documents. Note: Abstinence is acceptable if this is the established and preferred 
contraception for the patient. 
6. Male patient agrees to use an adequate method of contraception (see the study protocol for a 
list of acceptable birth control methods) and not donate sperm starting with the first dose of 
study treatment through 90 days after the last dose of study treatment. Note: Abstinence is 
acceptable if this is the established and preferred contraception for the patient. 
7. Patient has measurable lesions by RECIST v1.1. 
For Parts A and C, in addition to the general inclusion criteria, patients must also meet the following 
additional criteria to be considered eligible to participate in this study: 
8. Patient is able to take oral medications. 
9. For patients to be eligible for any parts of the study using niraparib 300 mg as a starting dose, 
a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 u/L is 
necessary. 
Main Criteria for Exclusion: 
Patients will not be eligible for the study entry if any of the following criteria are met: 
1. Patient has known active central nervous system metastases, carcinomatous meningitis, or 
both. Note: Patients with previously treated brain metastases may participate provided they 
are stable (without evidence of progression by imaging [using the identical imaging modality 
for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of 
study treatment and any neurologic symptoms have returned to baseline), have no evidence of 
new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to 
study treatment. Carcinomatous meningitis precludes a patient from study participation 
regardless of clinical stability. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 32 of 259 
 
2. Patient has a known additional malignancy that progressed or required active treatment within 
the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma 
of the skin that has undergone potentially curative therapy, or in situ cervical cancer. 
3. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, 
nonmalignant systemic disease, or active infection that requires systemic therapy. Specific 
examples include, but are not limited to, history of (noninfectious) pneumonitis that required 
steroids or current pneumonitis, uncontrolled ventricular arrhythmia, recent (within 90 days) 
myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, 
superior vena cava syndrome, or any psychiatric or substance abuse disorders that would 
interfere with cooperation with the requirements of the study (including obtaining informed 
consent). 
4. Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, 
or laboratory abnormality that might confound the study results or interfere with the patient’s 
participation for the full duration of the study treatment including the following:  
a. Patients who received a transfusion (platelets or red blood cells) within 6 weeks of the 
first dose of study treatment are not eligible. 
b. Patients who received colony-stimulating factors (e.g., granulocyte colony-stimulating 
factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) 
within 4 weeks prior to the first dose of study treatment are not eligible.  
5. Patient is pregnant or expecting to conceive children within the projected duration of the 
study, starting with the screening visit through 180 days after the last dose of study treatment. 
a. No data are available regarding the presence of niraparib or its metabolites in human milk, 
or on its effects on the breastfed infant or milk production. Because of the potential for 
serious adverse reactions in breastfed infants from niraparib, female patients should not 
breastfeed during treatment with niraparib and for 1 month after receiving the final dose. 
6. Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any 
other form of immunosuppressive therapy within 7 days prior to the first dose of study 
treatment. 
7. Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies). 
8. Patient has known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C 
(e.g., hepatitis C virus ribonucleic acid [qualitative] is detected). 
9. Patient has an active autoimmune disease that has required systemic treatment in the past 2 
years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive 
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of 
systemic treatment. 
10. Patient has not recovered (i.e., to Grade ≤1 or to baseline) from cytotoxic therapy-induced 
AEs. Note: Patients with Grade ≤2 neuropathy, Grade ≤2 alopecia, or Grade ≤2 fatigue are an 
exception to this criterion and may qualify for the study. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 33 of 259 
 
11. Patient is currently participating and receiving study treatment or has participated in a study of 
an investigational agent and received study treatment or used an investigational device within 
4 weeks of the first dose of treatment. 
12. Patient has had a prior cytotoxic therapy, anticancer targeted small molecules (e.g., tyrosine 
kinase inhibitors), hormonal agents within 5 half-lives, or monoclonal antibodies within 5 
half-lives or 4 weeks (whichever is shorter) of that treatment prior to Day 1; radiation therapy 
encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 
week prior to Day 1. 
13. Patient has not recovered adequately from AEs or complications from any major surgery prior 
to starting therapy. 
14. Patient has received prior therapy with an anti-programmed death 1, anti-programmed 
death-ligand 1 (PD-L1), anti-programmed death-ligand 2, anti-cytotoxic 
T-lymphocyte-associated antigen-4 antibody (including ipilimumab), or any other antibody or 
drug specifically targeting T-cell co-stimulation or checkpoint pathways. 
15. Patient has received a live vaccine within 14 days of planned start of study treatment.  
16. Patient has a heart-rate corrected QT interval (QTc) prolongation >480 ms at screening. Note: 
If a patient has a prolonged QT interval and the prolongation is deemed to be due to a 
pacemaker upon Investigator evaluation (i.e., the patient otherwise has no cardiac 
abnormalities), the patient may be eligible to participate in the study following discussion with 
the Sponsor’s Medical Monitor. 
17. Patient has a known hypersensitivity to TSR-042 components or excipients. 
For Parts A and C only, patients will not be eligible for study entry if any of the following additional 
exclusion criteria are met: 
18. Patient has undergone prior treatment with a known poly(ADP-ribose) polymerase inhibitor. 
19. Patient has a known hypersensitivity to niraparib components or excipients. 
20. Patient has had any known Grade 3 or 4 anemia, neutropenia, or thrombocytopenia due to 
prior chemotherapy that persisted >4 weeks related to the most recent prior treatment. 
21. Known history or current diagnosis of MDS or AML, or current diagnosis of prostate cancer. 
For Parts B, D, E, F, G, H, and I, patients will not be eligible for study entry if the following 
additional exclusion criterion is met: 
22. Patient has a known hypersensitivity to any of the following relevant study treatments: 
carboplatin, paclitaxel, pemetrexed, nab-paclitaxel, or TSR-022 components or excipients. 
For Parts C and D only, patients will not be eligible for study entry if any of the following additional 
exclusion criteria are met: 
23. Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction 
abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or 
unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, 
serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular 
disease, and history of cerebrovascular accident [CVA]) within 6 months of enrollment. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 34 of 259 
 
24. Patient has a history of bowel obstruction, including subocclusive disease, related to the 
underlying disease and history of abdominal fistula, gastrointestinal perforation, or 
intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or 
bowel involvement on CT scan or clinical symptoms of bowel obstruction. 
25. Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or 
urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at 
baseline should undergo 24-hour urine collection and must demonstrate <2 g of protein in 
24 hours to be eligible). 
26. Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or 
surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, 
transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage 
within the past 3 months). 
27. Patient has a known hypersensitivity to bevacizumab components or excipients. 
For Parts E and F only, patients will not be eligible for study entry if any of the following additional 
exclusion criteria are met: 
28. Patient is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs (NSAIDs), 
other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long -acting 
agents, such as piroxicam.  
29. Patient is unable or unwilling to take folic acid or vitamin B12 supplement  
30. Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable 
following treatment for these conditions (including therapeutic thoraco- or paracentesis) is 
eligible. 
For Parts G, H, and I only, patients will not be eligible for study entry if any of the following 
additional exclusion criteria are met: 
31. Patient has pre-existing peripheral neuropathy that is Grade ≥2 by Common Terminology 
Criteria for Adverse Events (CTCAE) version 4 criteria. 
For Parts E, F, G, H, and I only, patients will not be eligible for study entry if any of the following 
additional exclusion criteria are met: 
32. Patient has interstitial lung disease or a history of pneumonitis that required oral or 
intravenous glucocorticoids to assist with management 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 35 of 259 
 
Investigational Product, Dosage, and Mode of Administration: 
Niraparib 
Niraparib will be administered orally once daily (QD) continuously at the assigned dose. On Day 1 of 
each cycle, a niraparib dose will be administered upon completion of all infusions. Depending on the 
dose regimen, 2 or 3 capsules of 100-mg strength niraparib will be taken at each dose administration 
(total dose of 200 or 300 mg per dose, respectively). Subsequent to Amendment 1, only patients with a 
screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 μL will be eligible to 
receive niraparib 300 mg as a stating dose. Patients will be instructed to take their niraparib dose at the 
same time each day; bedtime administration may be a potential method for managing nausea. Patients 
must swallow and not chew all capsules. The consumption of water and food is permissible. 
Niraparib will be dispensed to patients on Day 1 of every 21-day cycle for up to 2 years or until 
disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. The 
Pharmacy Manual contains descriptions of the packaging of niraparib and instructions for the 
preparation and administration of niraparib. 
TSR-042 
TSR-042 will be administered at the study site by 30-minute intravenous (IV) infusion on Day 1 of 
every 21-day cycle (Q3W) at 500 mg for the first 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 
will be administered at 1,000 mg every other cycle (Q6W) to patients in Parts A, B, C, and D for up to 
2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, 
or death. Patients in Parts E, F, G, H, and I will continue to receive 500 mg on Day 1 of every cycle 
(Q3W) throughout the study. Continued treatment with TSR-042 beyond 2 years may be considered 
following discussion between the Sponsor and Investigator. The Pharmacy Manual contains 
descriptions of the packaging of TSR-042 and instructions for the preparation and administration of 
TSR-042. 
TSR-022 
TSR-022 will be administered at the study site by 30-minute IV infusion on Day 1 of every 21-day 
cycle (Q3W) at 900 mg (or 300 mg if lowered to dose level -1 for reasons of safety) for up to 2 years 
or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or 
death. Continued treatment with TSR-022 beyond 2 years may be considered following discussion 
between the Sponsor and Investigator. The Pharmacy Manual contains descriptions of the packaging 
of TSR-022 and instructions for the preparation and administration of TSR-022. 
Carboplatin-Paclitaxel 
Paclitaxel will be administered at the study site by a 3-hour IV infusion on Day 1 of every 21-day 
cycle (Q3W) at 175 mg/m2 for 4 to 6 cycles or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. The paclitaxel package insert contains descriptions of 
the packaging of paclitaxel and instructions for preparation and administration of paclitaxel. 
Carboplatin will be administered at the study site by a 30- or 60-minute IV infusion (30 minutes 
preferred) on Day 1 of every 21-day cycle (Q3W) at an area under the plasma or serum concentration-
time curve (AUC) of 5 or 6, and will be administered for 4 to 6 cycles as clinically indicated. The 
carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior 
anticancer therapies and pre-existing medical conditions. The carboplatin package insert contains 
descriptions of the packaging of carboplatin and instructions for preparation and administration of 
carboplatin.  
Carboplatin-Pemetrexed 
Pemetrexed will be administered at the study site by a 10-minute IV infusion on Day 1 of every 
21-day cycle (Q3W) at 500 mg/m2 for up to 2 years or until progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. The pemetrexed package insert contains descriptions of 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 36 of 259 
 
the packaging of pemetrexed and instructions for the preparation and administration of pemetrexed.  
Continued treatment with pemetrexed beyond 2 years may be considered following discussion 
between the Sponsor and Investigator. All patients should receive the appropriate supplementation of 
vitamin B12 and folic acid and corticosteroid prophylaxis as listed below: 
 
Folic acid 350 to 1,000 μg oral: At least 5 doses of folic acid must be taken during the 7 days 
preceding the first dose of pemetrexed, and folic acid dosing must continue during the full 
course of therapy and for 21 days after the last dose of pemetrexed. 
 
Vitamin B12 1,000 μg intramuscular injection will be administered in the week preceding the 
first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 
injections may be given the same day as pemetrexed administration.  
Carboplatin will be administered at the study site by a 30- or 60-minute IV infusion (30 minutes 
preferred) on Day 1 of every 21-day cycle (Q3W) at an AUC of 5 or 6, and will be administered for 4 
to 6 cycles as clinically indicated. The carboplatin dose will be determined by the Investigator, taking 
into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. The 
carboplatin package insert contains descriptions of the packaging of carboplatin and instructions for 
the preparation and administration of carboplatin.   
Carboplatin–Nab-Paclitaxel 
Nab-paclitaxel will be administered at the study site by a 30-minute IV infusion on Days 1, 8, and 15 
of every week (Q1W) of every 3-week cycle, at 100 mg/m2 for 4 to 6 cycles as clinically indicated or 
until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
The nab-paclitaxel package insert contains descriptions of the packaging of nab-paclitaxel and 
instructions for preparation and administration of nab-paclitaxel. 
Carboplatin will be administered at the study site by a 30- or 60-minute IV infusion (30 minutes 
preferred) on Day 1 of every 21-day cycle (Q3W) at an AUC of 5 or 6, and will be administered for 4 
to 6 cycles as clinically indicated. The carboplatin dose will be determined by the Investigator, taking 
into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. The 
carboplatin package insert contains descriptions of the packaging of carboplatin and instructions for 
preparation and administration of carboplatin. 
Bevacizumab 
Bevacizumab will be administrated at the study site by IV infusion based on local approved product 
label on Day 1 of every 21-day cycle (Q3W) at 15 mg/kg for up to 15 months or until progression, 
unacceptable toxicity, patient withdrawal, Investigator’s decision or death. The bevacizumab package 
insert contains descriptions of the packaging of bevacizumab and instructions for preparation and 
administration of bevacizumab. 
Note: The order of study drug administration for each part is listed below: 
 
Part A: TSR-042 followed by niraparib after completion of infusion 
 
Part B: TSR-042 followed by paclitaxel, then carboplatin 
 
Part C: TSR-042 followed by bevacizumab, then niraparib after completion of both infusions 
 
Part D: TSR-042 followed by paclitaxel, then carboplatin, then bevacizumab 
 
Part E: TSR-042 followed by pemetrexed, then carboplatin  
 
Part F: TSR-042 followed by TSR-022, then pemetrexed, then carboplatin 
 
Part G: TSR-042 followed by nab-paclitaxel, then carboplatin 
 
Part H: TSR-042 followed by TSR-022, then nab-paclitaxel, then carboplatin 
 
Part I: TSR-042 followed by TSR-022, then paclitaxel, then carboplatin 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 37 of 259 
 
Duration of Treatment: 
Planned Study Conduct Duration 
The primary analysis will occur at approximately 6 months after the last patient is enrolled. The final 
analysis of primary and secondary endpoints will be conducted approximately 12 months after the last 
patient is enrolled. 
Planned Study Treatment Duration 
Patients enrolled in Part A may continue TSR-042 and niraparib combination treatment for up to 
2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, 
or death. Patients who have not progressed at 2 years will be given the option to continue on TSR-042 
and niraparib combination treatment beyond 2 years if they are tolerating and benefiting from 
treatment and after consultation with the Sponsor. Patients with confirmed PD may continue study 
treatment at the Investigator’s discretion until the Investigator has determined that the patient is no 
longer experiencing clinical benefit or until study treatment is no longer tolerated by the patient. 
Patients enrolled in Part B may continue TSR-042 and carboplatin-paclitaxel combination treatment 
for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 monotherapy for up to 
2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, 
or death. Continued treatment with TSR-042 beyond 2 years may be considered following discussion 
between the Sponsor and Investigator. 
Patients enrolled in Part C may continue TSR-042, niraparib and bevacizumab combination treatment 
for up to 15 months. Subsequently, they may continue TSR-042 and niraparib combination treatment 
for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s 
decision, or death. Continued treatment with TSR-042 and niraparib beyond 2 years may be 
considered following discussion between the Sponsor and Investigator. 
Patients enrolled in Part D may continue TSR-042, carboplatin-paclitaxel, and bevacizumab 
combination treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 and 
bevacizumab treatment up to a total of 15 months. Subsequently, patients may continue TSR-042 
treatment alone for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. Continued treatment with TSR-042 beyond 2 years may 
be considered following discussion between the Sponsor and Investigator. 
Patients enrolled in Part E may continue TSR-042 and carboplatin-pemetrexed combination treatment 
for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 and pemetrexed for up to 
2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, 
or death. Continued treatment with TSR-042 and pemetrexed beyond 2 years may be considered 
following discussion between the Sponsor and Investigator. 
Patients enrolled in Part F may continue TSR-042, TSR-022, and carboplatin-pemetrexed combination 
treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042, TSR-022, and 
pemetrexed combination therapy for up to 2 years or until disease progression, unacceptable toxicity, 
patient withdrawal, Investigator’s decision, or death. Continued treatment with TSR-022, TSR-042, or 
pemetrexed beyond 2 years may be considered following discussion between the Sponsor and 
Investigator.  
Patients enrolled in Part G may continue TSR-042 and carboplatinnab-paclitaxel combination 
treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 monotherapy for 
up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s 
decision, or death. Continued treatment with TSR-042 beyond 2 years may be considered following 
discussion between the Sponsor and the Investigator. 
Patients enrolled in Part H may continue TSR-042, TSR-022, and carboplatin–nab-paclitaxel 
combination treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 and 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 38 of 259 
 
TSR-022 combination therapy for up to 2 years or until disease progression, unacceptable toxicity, 
patient withdrawal, Investigator’s decision, or death. Continued treatment with TSR-022 or TSR-042 
beyond 2 years may be considered following discussion between the Sponsor and the Investigator. 
Patients enrolled in Part I may continue TSR-042, TSR-022, and carboplatin-paclitaxel combination 
treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 and TSR-022 
combination therapy for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. Continued treatment with TSR-022 or TSR-042 beyond 
2 years may be considered following discussion between the Sponsor and the Investigator. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 39 of 259 
 
Criteria for Evaluation: 
Efficacy 
The following secondary efficacy endpoints will be evaluated based on Investigator assessment: 
 
ORR, defined as the proportion of patients who have achieved confirmed CR or PR, 
evaluated using RECIST v1.1 based on Investigator assessment  
 
DOR, defined as the time from first documentation of response (CR or PR) until the time 
of first documentation of disease progression by RECIST v1.1 based on Investigator 
assessment or death by any cause 
 
DCR, defined as the percentage of patients who have achieved CR, PR, or stable disease 
per RECIST v1.1 based on Investigator assessment 
 
PFS, defined as the time from the date of the first dose of study treatment to the earlier 
date of assessment of progression, or death by any cause in the absence of progression by 
RECIST v1.1 based on Investigator assessment 
Safety 
The primary endpoints in the safety analysis are as follows: 
 
Determination of the RP2D based on the number of DLTs observed during the first cycle 
(i.e., during the first 21 days of treatment [Day 1 to Day 21 of Cycle 1]). 
 
Incidence of treatment-emergent adverse events (TEAEs) occurring while patients are on 
treatment or up to 30 days after the last dose of study treatment 
 
Incidence of SAEs and adverse event of special interest (AESIs) occurring while patients 
are on study treatment or up to 90 days after the last dose of study treatment 
 
Changes in clinical laboratory parameters (hematology, serum chemistry, coagulation, 
thyroid function, and urinalysis), vital signs, ECOG performance status, ECG parameters 
(including QTc calculated using Fridericia’s [QTcF]), physical examinations, and use of 
concomitant medications 
Pharmacokinetics 
Plasma and serum samples for PK determination will be collected from all patients. 
For Part A (TSR-042 and niraparib combination treatment) and Part C (TSR-042, niraparib and 
bevacizumab combination treatment), plasma will be analyzed using liquid chromatography with mass 
spectrometry detection for niraparib and its major metabolite M1. The serum will be analyzed for 
TSR-042 using enzyme-linked immunosorbent assay (ELISA).  
For Part B (TSR-042 and carboplatin-paclitaxel combination treatment), Part D (TSR-042, 
carboplatin-paclitaxel and bevacizumab combination treatment), Part E (TSR-042 and carboplatin-
pemetrexed combination treatment), Part F (TSR-042, TSR-022, and carboplatin-pemetrexed 
combination treatment), Part G (TSR-042 and carboplatin–nab-paclitaxel combination treatment), 
Part H (TSR-042, TSR-022, and carboplatin–nab-paclitaxel), and Part I (TSR-042, TSR-022, and 
carboplatin-paclitaxel) serum samples will be analyzed for TSR-042 and TSR-022 using ELISA. The 
plasma samples will be analyzed for carboplatin using inductively coupled plasma mass spectrometry, 
and for paclitaxel and pemetrexed using liquid chromatography tandem-mass spectrometry, if 
appropriate. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 40 of 259 
 
Parameters of interest are AUC, minimum observed plasma or serum concentration (Cmin), maximum 
observed plasma or serum concentration (Cmax), clearance (after oral administration [CL/F] and after 
IV administration [CL]), volume of distribution (after oral administration [Vz/F] and after IV 
administration [Vz]), AUC at steady state (AUCss), minimum observed plasma or serum concentration 
at steady state (Cmin,ss), and maximum observed plasma or serum concentration at steady state (Cmax,ss). 
Immunogenicity 
Serum samples for the determination of TSR-042 and TSR-022 ADAs will be the same blood 
collections as those for the TSR-042 and TSR-022 PK assessments. ADAs will be analyzed in a tiered 
approach using electrochemiluminescence (i.e., screening, confirmation, titer, and competitive ligand 
binding assay as neutralizing antibody assay). Minimally, ADAs will be analyzed in predose samples 
from all cycles collected; additional samples for ADA determination will be collected upon treatment 
discontinuation at a post-treatment and safety follow-up visit (i.e., approximately 90 days after the last 
dose of TSR-042/TSR-022). 
Biomarkers 
Archival FFPE tumor tissue (mandatory [if available] for Parts F, H, and I; optional for Parts A, B, C, 
D, E, and G) and blood samples will be assessed for biomarkers that may correlate with clinical 
benefit from treatment with TSR-042 and niraparib combination treatment (Part A); TSR-042 and 
carboplatin-paclitaxel combination treatment (Part B); TSR-042, niraparib, and bevacizumab 
combination treatment (Part C); TSR-042, carboplatin-paclitaxel, and bevacizumab combination 
treatment (Part D); TSR-042 and carboplatin-pemetrexed combination treatment (Part E); TSR-042, 
TSR-022, and carboplatin-pemetrexed combination treatment (Part F); TSR-042 and carboplatin–
nab-paclitaxel combination treatment (Part G); TSR-042, TSR-022, and carboplatin–nab-paclitaxel 
combination treatment (Part H); and TSR-042, TSR-022, and carboplatin-paclitaxel combination 
treatment (Part I), including but not limited to germline BRCA mutation (gBRCAmut), homologous 
recombination deficiency status, the phenotype and molecular profile of circulating immune cells, and 
circulating cytokines or chemokines prior to and during treatment. To enable these evaluations, blood 
samples for biomarker analysis will be obtained in Parts A, B, C, and D at the time of screening, at 
predose on Day 1 of Cycles 1 and 2, and at the time of EOT visit or disease progression. Blood 
samples for biomarker analysis will be obtained in Parts E, F, G, H, and I at the time of screening, at 
predose on Days 1 and 15 of Cycle 1 and Day 1 of Cycles 2, 4, and 6, and at the EOT visit or time of 
disease progression. 
Statistical Methods: 
Sample Size Considerations 
Part A: An initial sample size of approximately 12 to 24 patients is estimated for Part A of the study to 
provide an initial understanding of the incidence of DLTs and safety profiles of TSR-042 and 
niraparib combination treatment.  
Part B: A total of approximately 12 patients will be enrolled in Part B of the study to provide an initial 
understanding of the safety profiles of TSR-042 and carboplatin-paclitaxel combination treatment. 
Part C: A sample size of approximately 6 to 24 patients is estimated for Part C of the study to provide 
an initial understanding of the incidence of DLTs and safety profiles of TSR-042, niraparib and 
bevacizumab combination treatment. 
Part D: A total of approximately 6 to 12 patients will be enrolled in Part D of the study to provide an 
initial understanding of the safety profiles of TSR-042, carboplatin-paclitaxel and bevacizumab 
combination treatment. 
Part E: A total of approximately 6 to 12 patients will be enrolled in Part E of the study to provide an 
initial understanding of the safety profiles of TSR-042 and carboplatin-pemetrexed combination 
treatment. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 41 of 259 
 
Part F: A total of approximately 6 to 24 patients will be enrolled in Part F of the study to provide an 
initial understanding of the safety profiles of TSR-042, TSR-022, and carboplatin-pemetrexed 
combination treatment. 
Part G: A total of approximately 6 to 12 patients will be enrolled in Part G of the study to provide an 
initial understanding of the safety profiles of TSR-042 and carboplatin–nab-paclitaxel combination 
treatment. 
Part H: A total of approximately 6 to 24 patients will be enrolled in Part H of the study to provide an 
initial understanding of the safety profiles of TSR-042, TSR-022, and carboplatin–nab-paclitaxel 
combination treatment. 
Part I: A total of approximately 6 to 24 patients will be enrolled in Part I of the study to provide an 
initial understanding of the safety profiles of TSR-042, TSR-022, and carboplatin-paclitaxel 
combination treatment. 
Analysis Populations 
Three analysis populations will be defined as follows: 
 
Safety population: All patients who receive any amount of study treatment. All safety 
endpoints will be assessed in the safety population, with the exception of DLT 
assessment, which will include only those patients completing the first cycle of therapy, 
unless the patient discontinued study treatment due to a DLT. Analyses of baseline 
characteristics and the primary analysis of efficacy endpoints will be performed on the 
safety population. 
 
PK population: All patients who receive at least 1 dose of study treatment and have at 
least 1 PK sample. 
 
ADA population: All patients who receive at least 1 dose of study treatment and have 
provided a predose blood sample and at least 1 postdose blood sample at or after 96 hours. 
General Methods 
All analyses will include summary statistics, including the number and percentage for categorical 
variables and the number of patients, mean, standard deviation, median, minimum, and maximum for 
continuous variables. Time-to-event analyses will be performed using Kaplan-Meier methods. Further 
details will be provided in the study statistical analysis plan. 
Efficacy Analysis 
ORR and DCR will be summarized using descriptive statistics, including the number, percentage, and 
2-sided 90% confidence intervals (CIs). 
DOR and PFS will be summarized using Kaplan-Meier analysis, including the number and percentage 
of events, number and percentage of censored patients, and the 25th, 50th, and 75th percentiles of 
times-to-event with 95% CIs. 
Safety Analysis 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) for purposes of 
summarization. All AEs occurring during the study will be included in by-patient data listings and 
tabulated by MedDRA system organ class (SOC) and preferred term. Safety endpoints for AEs 
include the following: incidence of DLTs, TEAEs, AESIs, and SAEs. Tabulations will be produced by 
MedDRA SOC and preferred term. Tabulations of TEAEs will also be produced by severity and by 
relationship to study treatment. 
Additional safety summaries will be provided for clinical laboratory tests, vital signs, ECOG 
performance status, ECGs, physical examinations, and usage of concomitant medications. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 42 of 259 
 
Pharmacokinetics Analysis 
The analysis set for the PK parameters will be the PK population. Noncompartmental methods will be 
used to evaluate the PK characteristics as appropriate.  
Immunogenicity Analysis 
The analysis set for ADA analyses will be the ADA population. The number and percent of patients 
who become positive for ADAs and who develop neutralizing antibodies will be summarized by dose 
and regimen, by visit, and overall. 
Biomarkers Analysis 
The incidence of biomarkers will be summarized using descriptive statistics. Comparisons of efficacy 
endpoints between biomarker subpopulations may be performed. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 43 of 259 
 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
SPONSOR SIGNATURE PAGE ....................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
1. 
SYNOPSIS ...................................................................................................................4 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............43 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................55 
4. 
INTRODUCTION ......................................................................................................59 
4.1. 
Background .................................................................................................................59 
4.1.1. 
PARP and Homologous Recombination Deficiency ..................................................59 
4.1.2. 
Immune Surveillance and PD-1 Inhibitors .................................................................60 
4.1.3. 
Anti-TIM-3 Monoclonal Antibody .............................................................................61 
4.1.4. 
Carboplatin-Paclitaxel Chemotherapy ........................................................................62 
4.1.5. 
Carboplatin-Pemetrexed Chemotherapy .....................................................................62 
4.1.6. 
Carboplatin–Nab-Paclitaxel Chemotherapy ...............................................................63 
4.1.7. 
Bevacizumab ...............................................................................................................63 
4.2. 
Study Treatments ........................................................................................................64 
4.2.1. 
Niraparib .....................................................................................................................64 
4.2.1.1. 
Nonclinical Experience ...............................................................................................64 
4.2.1.2. 
Clinical Experience .....................................................................................................64 
4.2.2. 
TSR-042 ......................................................................................................................67 
4.2.2.1. 
Nonclinical Experience ...............................................................................................67 
4.2.2.2. 
Clinical Experience .....................................................................................................68 
4.2.3. 
TSR-022 ......................................................................................................................69 
4.2.3.1. 
Nonclinical Experience ...............................................................................................69 
4.2.3.2. 
Clinical Experience .....................................................................................................70 
4.2.4. 
Bevacizumab ...............................................................................................................71 
4.2.4.1. 
Clinical Experience .....................................................................................................71 
4.2.5. 
TSR-042 and Niraparib Combination Treatment .......................................................71 
4.2.5.1. 
Nonclinical Experience ...............................................................................................71 
4.2.5.2. 
Clinical Experience .....................................................................................................72 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 44 of 259 
 
4.2.6. 
Carboplatin-Paclitaxel in Combination With PD-1 or PD-L1 Antibodies .................72 
4.2.6.1. 
Nonclinical Experience ...............................................................................................72 
4.2.6.2. 
Clinical Experience .....................................................................................................72 
4.2.7. 
Carboplatin-Paclitaxel in Combination with Bevacizumab .......................................73 
4.2.8. 
Carboplatin-Pemetrexed in Combination With Anti-PD-1 Inhibitors ........................73 
4.2.9. 
Carboplatin–Nab-Paclitaxel in Combination With Anti-PD-1 Inhibitors ..................74 
4.2.10. 
Combination of Niraparib and Bevacizumab .............................................................74 
4.2.11. 
Combination of PD-L1 Inhibitor, PARP Inhibitor, and Anti-Angiogenic 
Agent ...........................................................................................................................75 
4.2.12. 
Combination of TSR-042 and TSR-022 .....................................................................75 
4.3. 
Rationale for the Current Study ..................................................................................76 
5. 
STUDY OBJECTIVES AND PURPOSE ..................................................................78 
5.1. 
Primary Objectives .....................................................................................................78 
5.2. 
Secondary Objectives .................................................................................................79 
5.3. 
Exploratory Objectives ...............................................................................................81 
6. 
INVESTIGATIONAL PLAN .....................................................................................84 
6.1. 
Overall Study Design and Plan ...................................................................................84 
6.1.1. 
Overview .....................................................................................................................86 
6.1.2. 
General Study Conduct ...............................................................................................88 
6.1.2.1. 
Part A: Dose Finding for TSR-042 and Niraparib Combination Treatment ..............88 
6.1.2.2. 
Part B: Safety and Tolerability Evaluation for TSR-042 and 
Carboplatin-Paclitaxel Combination Treatment .........................................................90 
6.1.2.3. 
Part C: Dose Finding for TSR-042, Niraparib, and Bevacizumab 
Combination Treatment ..............................................................................................91 
6.1.2.4. 
Part D: Safety and Tolerability Evaluation for TSR-042, Carboplatin-
Paclitaxel and Bevacizumab Combination Treatment ................................................94 
6.1.2.5. 
Part E: Safety and Tolerability for TSR-042 and Carboplatin-Pemetrexed 
Combination Treatment ..............................................................................................96 
6.1.2.6. 
Part F: Safety and Tolerability for TSR-042, TSR-022, and Carboplatin-
Pemetrexed Combination Treatment ..........................................................................98 
6.1.2.7. 
Part G: Safety and Tolerability for TSR-042 and Carboplatin–Nab-Paclitaxel 
Combination Treatment ............................................................................................100 
6.1.2.8. 
Part H: Safety and Tolerability for TSR-042, TSR-022, and Carboplatin–
Nab-Paclitaxel Combination Treatment ...................................................................102 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy 
Clinical Study Protocol Study 3000-01-002 Version 3.0 
Confidential 
Page 45 of 259 
6.1.2.9. 
Part I: Safety and Tolerability for TSR-042, TSR-022, and Carboplatin-
Paclitaxel Combination Treatment ...........................................................................104 
6.1.2.10. 
Dose-Limiting Toxicity Assessment ........................................................................106 
6.2. 
Number of Subjects ..................................................................................................107 
6.3. 
Treatment Assignment ..............................................................................................107 
6.3.1. 
Part A: Dose Finding for TSR-042 and Niraparib Combination Treatment ............107 
6.3.2. 
Part B: TSR-042 and Carboplatin-Paclitaxel Combination Treatment Safety 
and Tolerability .........................................................................................................107 
6.3.3. 
Part C: Dose Finding for TSR-042, Niraparib, and Bevacizumab 
Combination Treatment ............................................................................................107 
6.3.4. 
Part D: TSR-042, Carboplatin-Paclitaxel, and Bevacizumab Combination 
Treatment ..................................................................................................................107 
6.3.5. 
Part E: TSR-042 and Carboplatin-Pemetrexed Combination Treatment .................107 
6.3.6. 
Part F: TSR-042, TSR-022, and Carboplatin-Pemetrexed Combination 
Treatment ..................................................................................................................108 
6.3.7. 
Part G: TSR-042 and Carboplatin–Nab-Paclitaxel Combination Treatment ...........108 
6.3.8. 
Part H: TSR-042, TSR-022, and Carboplatin–Nab-Paclitaxel Combination 
Treatment ..................................................................................................................108 
6.3.9. 
Part I: TSR-042, TSR-022, and Carboplatin-Paclitaxel Combination 
Treatment ..................................................................................................................108 
6.4. 
Dose Adjustment Criteria .........................................................................................108 
6.4.1. 
Safety Criteria for Adjustment or Stopping Doses ...................................................108 
6.4.1.1. 
Niraparib ...................................................................................................................108 
6.4.1.2. 
TSR-042 and TSR-022 .............................................................................................111 
6.4.1.3. 
Carboplatin-Paclitaxel ..............................................................................................113 
6.4.1.4. 
Carboplatin-Pemetrexed ...........................................................................................113 
6.4.1.5. 
Carboplatin–Nab-Paclitaxel ......................................................................................113 
6.4.1.6. 
Bevacizumab .............................................................................................................114 
6.4.2. 
Pharmacokinetic Criteria for Adjustment or Stopping Doses ..................................114 
6.5. 
Criteria for Study Termination .................................................................................114 
7. 
STUDY POPULATION ...........................................................................................115 
7.1. 
Inclusion Criteria ......................................................................................................115 
7.2. 
Exclusion Criteria .....................................................................................................116 
7.3. 
Patient Discontinuation and Replacement ................................................................120 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 46 of 259 
 
7.3.1. 
Discontinuation from Study Treatment ....................................................................120 
7.3.2. 
Discontinuation from the Study ................................................................................121 
7.3.3. 
Replacement of Patients ...........................................................................................121 
7.4. 
Patient Identification and Randomization ................................................................121 
7.4.1. 
Patient Identification .................................................................................................121 
7.4.2. 
Randomization Scheme ............................................................................................121 
8. 
TREATMENT OF PATIENTS ................................................................................122 
8.1. 
Description of Study Drug ........................................................................................122 
9. 
STUDY DRUG MATERIALS AND MANAGEMENT .........................................124 
9.1. 
Identity ......................................................................................................................124 
9.1.1. 
Niraparib ...................................................................................................................124 
9.1.2. 
TSR-042 ....................................................................................................................124 
9.1.3. 
TSR-022 ....................................................................................................................124 
9.1.4. 
Carboplatin-Paclitaxel ..............................................................................................124 
9.1.4.1. 
Carboplatin ...............................................................................................................124 
9.1.4.2. 
Paclitaxel ...................................................................................................................124 
9.1.5. 
Pemetrexed ...............................................................................................................124 
9.1.6. 
Nab-Paclitaxel ...........................................................................................................124 
9.1.7. 
Bevacizumab .............................................................................................................125 
9.2. 
Administration ..........................................................................................................125 
9.2.1. 
Niraparib ...................................................................................................................125 
9.2.2. 
TSR-042 ....................................................................................................................125 
9.2.3. 
TSR-022 ....................................................................................................................126 
9.2.4. 
Carboplatin-Paclitaxel ..............................................................................................126 
9.2.5. 
Carboplatin-Pemetrexed ...........................................................................................126 
9.2.6. 
Carboplatin–Nab-Paclitaxel ......................................................................................127 
9.2.7. 
Bevacizumab .............................................................................................................127 
9.2.8. 
Order of Administration ...........................................................................................128 
9.3. 
Dose Modification ....................................................................................................128 
9.4. 
Study Drug Packaging, Labeling, and Storage .........................................................128 
9.5. 
Study Drug Accountability .......................................................................................128 
9.6. 
Study Drug Handling and Disposal ..........................................................................129 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 47 of 259 
 
9.7. 
Previous and Concomitant Medications ...................................................................129 
9.7.1. 
Recording of Previous and Concomitant Medications .............................................129 
9.7.2. 
Prohibited Medications .............................................................................................129 
9.7.3. 
Contraception ............................................................................................................131 
9.7.4. 
Rescue Medications and Supportive Care Guidelines ..............................................131 
9.7.4.1. 
Pneumonitis ..............................................................................................................132 
9.7.4.2. 
Diarrhea/Colitis .........................................................................................................132 
9.7.4.3. 
Type 1 Diabetes Mellitus or Grade 3 or 4 Hyperglycemia .......................................132 
9.7.4.4. 
Hypophysitis .............................................................................................................132 
9.7.4.5. 
Hyperthyroidism or Hypothyroidism .......................................................................133 
9.7.4.6. 
Hepatitis ....................................................................................................................133 
9.7.4.7. 
Renal Failure or Nephritis ........................................................................................133 
9.7.4.8. 
Management of Infusion-Related Reactions ............................................................133 
9.7.5. 
Other Study Restrictions ...........................................................................................135 
9.8. 
Treatment Compliance ..............................................................................................135 
10. 
ENDPOINTS AND METHODS OF ASSESSMENT .............................................136 
10.1. 
Efficacy Endpoints ....................................................................................................136 
10.1.1. 
Evaluation of Tumor Response ................................................................................136 
10.1.1.1. 
Overview ...................................................................................................................136 
10.1.1.2. 
Timing of Radiographic Evaluations ........................................................................136 
10.1.1.3. 
Assessment of Response by RECIST v1.1 ...............................................................137 
10.1.2. 
Secondary Endpoints ................................................................................................137 
10.1.2.1. 
Objective Response Rate ..........................................................................................137 
10.1.2.2. 
Duration of Response ...............................................................................................138 
10.1.2.3. 
Disease Control Rate ................................................................................................138 
10.1.2.4. 
Progression-Free Survival ........................................................................................138 
10.2. 
Pharmacokinetic Assessments ..................................................................................138 
10.3. 
Immunogenicity Assessments ..................................................................................138 
10.4. 
Biomarker Assessments ............................................................................................139 
10.5. 
Use of Remaining Study Patient Specimens/Samples ..............................................140 
10.6. 
Safety Endpoints .......................................................................................................140 
10.6.1. 
Definitions ................................................................................................................140 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 48 of 259 
 
10.6.1.1. 
Adverse Event (AE) ..................................................................................................140 
10.6.1.2. 
Serious Adverse Event (SAE) ..................................................................................140 
10.6.1.3. 
Treatment-Emergent Adverse Event (TEAE) ..........................................................141 
10.6.1.4. 
Adverse Event of Special Interest (AESI) ................................................................141 
10.6.1.5. 
Special Situations: Abuse, Misuse, Medication Errors, Overdose, and 
Accidental or Occupational Exposure ......................................................................141 
10.6.2. 
Assessment of Adverse Events .................................................................................142 
10.6.2.1. 
Severity Assessment .................................................................................................142 
10.6.2.2. 
Relationship to Study Intervention ...........................................................................142 
10.6.2.3. 
Expectedness .............................................................................................................143 
10.6.3. 
Collection and Recording Adverse Events ...............................................................143 
10.6.4. 
Follow-Up of Adverse Events ..................................................................................144 
10.6.5. 
Reporting ..................................................................................................................144 
10.6.6. 
Submission and Distribution of Serious Adverse Event Reports .............................144 
10.6.7. 
Adverse Events of Special Interest ...........................................................................144 
10.6.7.1. 
Niraparib ...................................................................................................................144 
10.6.7.2. 
TSR-042 ....................................................................................................................145 
10.6.7.3. 
TSR-022 ....................................................................................................................145 
10.6.8. 
Pregnancy .................................................................................................................145 
10.6.9. 
Special Situations ......................................................................................................146 
10.6.10. 
Clinical Laboratory Assessments .............................................................................146 
10.6.11. 
Physical Examination and Vital Signs ......................................................................147 
10.6.12. 
Eastern Cooperative Oncology Group Performance Status ......................................147 
10.6.13. 
Additional Safety Assessments.................................................................................148 
10.7. 
Demographics and Baseline Characteristics .............................................................148 
10.7.1. 
Patient Eligibility ......................................................................................................148 
10.7.2. 
Patient Demography .................................................................................................148 
10.7.3. 
Disease History .........................................................................................................148 
10.7.4. 
Medical and Surgical History ...................................................................................149 
10.7.5. 
Previous and Concomitant Medications ...................................................................149 
11. 
STUDY CONDUCT .................................................................................................150 
11.1. 
Schedule of Events ...................................................................................................150 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 49 of 259 
 
11.2. 
Procedures by Visit ...................................................................................................228 
11.2.1. 
Screening Visit ..........................................................................................................228 
11.2.2. 
Cycle 1 ......................................................................................................................229 
11.2.3. 
Cycles 2 through 6 and Subsequent Cycles ..............................................................231 
11.2.3.1. 
Cycle 2 ......................................................................................................................233 
11.2.3.2. 
Cycle 4 ......................................................................................................................234 
11.2.3.3. 
Cycle 5 ......................................................................................................................234 
11.2.3.4. 
Cycle 6 ......................................................................................................................235 
11.2.3.5. 
Cycle 7 ......................................................................................................................235 
11.2.3.6. 
Cycle 11 ....................................................................................................................235 
11.2.3.7. 
Cycle 12 ....................................................................................................................236 
11.2.3.8. 
Cycle 13 ....................................................................................................................236 
11.2.4. 
End of Treatment ......................................................................................................236 
11.2.5. 
Safety Follow-up ......................................................................................................237 
11.2.5.1. 
30 Days ± 7 Days Post-treatment .............................................................................237 
11.2.5.2. 
90 Days ± 7 Days Post-treatment .............................................................................238 
11.2.6. 
Survival Assessment .................................................................................................238 
11.2.7. 
Unscheduled Visits ...................................................................................................239 
12. 
STATISTICAL METHODS .....................................................................................240 
12.1. 
Study Population .......................................................................................................240 
12.2. 
Demographics, Baseline Characteristics, Medical History, and Concomitant 
Medications ...............................................................................................................240 
12.3. 
Efficacy Analyses .....................................................................................................240 
12.3.1. 
General Methods .......................................................................................................240 
12.3.2. 
Secondary Efficacy Parameter(s) .............................................................................241 
12.4. 
Safety Analyses ........................................................................................................241 
12.5. 
Pharmacokinetic Analyses ........................................................................................242 
12.6. 
Immunogenicity Analyses ........................................................................................242 
12.7. 
Biomarker Analyses ..................................................................................................242 
12.8. 
Determination of Sample Size ..................................................................................242 
13. 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS ..................................244 
13.1. 
Data Quality Assurance ............................................................................................244 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 50 of 259 
 
13.2. 
Access to Source Data/Documents ...........................................................................244 
13.3. 
Archiving Study Documents .....................................................................................245 
13.4. 
Good Clinical Practice ..............................................................................................245 
13.5. 
Informed Consent .....................................................................................................245 
13.6. 
Protocol Approval and Amendment .........................................................................245 
13.7. 
Patient Confidentiality and Data Protection .............................................................246 
13.8. 
Study Monitoring ......................................................................................................246 
13.9. 
Audits and Inspections ..............................................................................................246 
13.10. 
Ethical Considerations ..............................................................................................246 
13.11. 
Publication Policy .....................................................................................................247 
13.12. 
Study Committee ......................................................................................................247 
14. 
LIST OF REFERENCES ..........................................................................................248 
APPENDIX A. DRUGS KNOWN TO INHIBIT OR INDUCE OR ARE 
SUBSTRATES OF CYP450 ISOZYMES ...............................................................256 
APPENDIX B. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
VERSION 1.1 ...........................................................................................................257 
APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS .....................................................................................259 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 51 of 259 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................55 
Table 2: 
Dose Regimen for TSR-042 and Niraparib Combination Treatment .........................88 
Table 3: 
Dose Regimen for TSR-042 and Carboplatin-Paclitaxel Combination 
Treatment ....................................................................................................................90 
Table 4: 
Dose Regimen for TSR-042, Niraparib and Bevacizumab Combination 
Treatment ....................................................................................................................92 
Table 5: 
Dose Regimen for TSR-042 and Carboplatin-Paclitaxel Combination 
Treatment ....................................................................................................................94 
Table 6: 
Dose Regimen for TSR-042 and Carboplatin-Pemetrexed Combination 
Treatment ....................................................................................................................96 
Table 7: 
Dose Regimen for TSR-042, TSR-022, and Carboplatin-Pemetrexed 
Combination Treatment ..............................................................................................98 
Table 8: 
Dose Regimen for TSR-042 and Carboplatin–Nab-Paclitaxel Combination 
Treatment ..................................................................................................................100 
Table 9: 
Dose Regimen for TSR-042, TSR-022, and Carboplatin–Nab-Paclitaxel 
Combination Treatment ............................................................................................102 
Table 10: Dose Regimen for TSR-042, TSR-022, and Carboplatin-Paclitaxel 
Combination Treatment ............................................................................................104 
Table 11: Niraparib Dose Modifications for Nonhematologic Adverse Reactions ..................109 
Table 12: Niraparib Dose Reductions for Nonhematologic Toxicity .......................................109 
Table 13: Niraparib Dose Modifications for Hematologic Toxicity ........................................110 
Table 14: Guidelines for Treatment of Immune-related Adverse Events of Interest ...............112 
Table 15: Investigational Product .............................................................................................122 
Table 16: TSR-042 and TSR-022 Infusion Reaction Treatment Guidelines ............................133 
Table 17: Schedule of Events - Part A - TSR-042 + Niraparib- Screening and Cycle 1 
Through Cycle 4 .......................................................................................................151 
Table 18: Schedule of Events - Part A - TSR-042 + Niraparib - Cycle 5 Through End 
of Study .....................................................................................................................153 
Table 19: Schedule of Events - Part B – TSR-042 + Carboplatin-Paclitaxel - Screening 
and Cycle 1 Through Cycle 4 ...................................................................................155 
Table 20: Schedule of Events - Part B – TSR-042 + Carboplatin-Paclitaxel - Cycle 5 
Through End of Study ..............................................................................................157 
Table 21: Schedule of Events - Part C - TSR-042 + Niraparib + Bevacizumab - 
Screening and Cycle 1 Through Cycle 4 ..................................................................160 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 52 of 259 
 
Table 22: Schedule of Events - Part C – TSR-042 + Niraparib + Bevacizumab - Cycle 
5 Through End of Study ...........................................................................................163 
Table 23: Schedule of Events - Part D – TSR-042 + Carboplatin-Paclitaxel + 
Bevacizumab - Screening and Cycle 1 Through Cycle 4 .........................................166 
Table 24: Schedule of Events - Part D – TSR-042 + Carboplatin-Paclitaxel + 
Bevacizumab -Cycle 5 Through End of Study .........................................................169 
Table 25: Schedule of Events - Part E – TSR-042 + Carboplatin-Pemetrexed - 
Screening and Cycle 1 Through Cycle 4 ..................................................................172 
Table 26: Schedule of Events - Part E – TSR-042 + Carboplatin-Pemetrexed - Cycle 5 
Through End of Study ..............................................................................................174 
Table 27: Schedule of Events - Part F – TSR-042 + TSR-022 + Carboplatin-
Pemetrexed - Screening and Cycle 1 Through Cycle 4 ............................................176 
Table 28: Schedule of Events - Part F – TSR-042 + TSR-022 + Carboplatin-
Pemetrexed - Cycle 5 Through End of Study ...........................................................179 
Table 29: Schedule of Events - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - 
Screening and Cycle 1 Through Cycle 4 ..................................................................182 
Table 30: Schedule of Events - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - 
Cycle 5 Through End of Study .................................................................................184 
Table 31: Schedule of Events - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-
Paclitaxel - Screening and Cycle 1 Through Cycle 4 ...............................................187 
Table 32: Schedule of Events - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-
Paclitaxel - Cycle 5 Through End of Study ..............................................................190 
Table 33: Schedule of Events - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - 
Screening and Cycle 1 Through Cycle 4 ..................................................................193 
Table 34: Schedule of Events - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - 
Cycle 5 Through End of Study .................................................................................196 
Table 35: PK and ADA Blood Sampling and ECG Schedule - Part A - TSR-042 + 
Niraparib- Screening and Cycle 1 Through Cycle 4 ................................................199 
Table 36: PK and ADA Blood Sampling and ECG Schedule - Part A - TSR-042 + 
Niraparib- Cycle 5 Through End of Treatment ........................................................200 
Table 37: PK and ADA Blood Sampling and ECG Schedule - Part B – TSR-042 + 
Carboplatin-Paclitaxel - Screening and Cycle 1 through Cycle 4 ............................201 
Table 38: PK and ADA Blood Sampling and ECG Schedule - Part B – TSR-042 + 
Carboplatin-Paclitaxel - Cycle 5 Through End of Treatment ...................................203 
Table 39: PK and ADA Blood Sampling and ECG Schedule - Part C - TSR-042 + 
Niraparib + Bevacizumab - Screening and Cycle 1 Through Cycle 4 .....................204 
Table 40: PK and ADA Blood Sampling and ECG Schedule - Part C - TSR-042 + 
Niraparib + Bevacizumab - Cycle 5 Through End of Treatment .............................205 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 53 of 259 
 
Table 41: PK and ADA Blood Sampling and ECG Schedule - Part D – TSR-042 + 
Carboplatin-Paclitaxel + Bevacizumab - Screening and Cycle 1 through 
Cycle 4 ......................................................................................................................206 
Table 42: PK and ADA Blood Sampling and ECG Schedule - Part D – TSR-042 + 
Carboplatin-Paclitaxel + Bevacizumab - Cycle 5 Through End of Treatment .........208 
Table 43: PK and ADA Blood Sampling and ECG Schedule - Part E – TSR-042 + 
Carboplatin-Pemetrexed - Screening and Treatment Cycles ....................................209 
Table 44: PK and ADA Blood Sampling and ECG Schedule - Part F – TSR-042 + 
TSR-022 + Carboplatin-Pemetrexed - Screening and Treatment Cycles .................211 
Table 45: PK and ADA Blood Sampling and ECG Schedule - Part G – TSR-042 + 
Carboplatin–Nab-Paclitaxel - Screening and Treatment Cycles ..............................213 
Table 46: PK and ADA Blood Sampling and ECG Schedule - Part H – TSR-042 + 
TSR-022 + Carboplatin–Nab-Paclitaxel - Screening and Treatment Cycles ...........215 
Table 47: PK and ADA Blood Sampling and ECG Schedule - Part I – TSR-042 + 
TSR-022 + Carboplatin-Paclitaxel - Screening and Treatment Cycles ....................217 
Table 48: TSR-042 and Niraparib Combination Treatment Administration and 
Dispensation/Collection - Part A ..............................................................................219 
Table 49: TSR-042 and Carboplatin-Paclitaxel Combination Treatment Administration 
- Part B ......................................................................................................................220 
Table 50: TSR-042, Niraparib, and Bevacizumab Combination Treatment 
Administration and Dispensation/Collection- Part C ...............................................221 
Table 51: TSR-042, Carboplatin-Paclitaxel, and Bevacizumab Combination Treatment 
Administration - Part D ............................................................................................222 
Table 52: TSR-042 and Carboplatin-Pemetrexed Combination Treatment 
Administration - Part E .............................................................................................223 
Table 53: TSR-042, TSR-022, and Carboplatin-Pemetrexed Combination Treatment 
Administration - Part F .............................................................................................224 
Table 54: TSR-042 and Carboplatin–Nab-Paclitaxel Combination Treatment 
Administration - Part G ............................................................................................225 
Table 55: TSR-042, TSR-022, and Carboplatin–Nab-Paclitaxel Combination 
Treatment Administration - Part H ...........................................................................226 
Table 56: TSR-042, TSR-022, and Carboplatin-Paclitaxel Combination Treatment 
Administration - Part I ..............................................................................................227 
Table 57: Drugs Known to Inhibit or Induce or are Substrates of CYP3A4 or CYP2C8 ........256 
Table 58: RECIST v1.1 Response for Patients with Measurable Disease (i.e., Target 
Disease) .....................................................................................................................258 
Table 59: RECIST v1.1 Response for Patients With Nonmeasurable Disease 
(i.e., Nontarget Disease) ...........................................................................................258 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 54 of 259 
 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................86 
Figure 2: 
Part A Dose-Finding Scheme for TSR-042 and Niraparib Combination 
Treatment ....................................................................................................................89 
Figure 3: 
Part B Dose Confirmation Scheme for TSR-042 and Carboplatin-Paclitaxel 
Combination Treatment ..............................................................................................91 
Figure 4: 
Part C Dose-Finding Scheme for TSR-042, Niraparib, and Bevacizumab 
Combination Treatment ..............................................................................................93 
Figure 5: 
Part D Dose Confirmation Scheme for TSR-042, Carboplatin-Paclitaxel and 
Bevacizumab Combination Treatment .......................................................................95 
Figure 6: 
Part E Dose Confirmation Scheme for TSR-042 and Carboplatin-Pemetrexed 
Combination Treatment ..............................................................................................97 
Figure 7: 
Part F Dose Confirmation Scheme for TSR-042, TSR-022, and Carboplatin-
Pemetrexed Combination Treatment ..........................................................................99 
Figure 8: 
Part G Dose Confirmation Scheme for TSR-042 and Carboplatin–
Nab-Paclitaxel Combination Treatment ...................................................................101 
Figure 9: 
Part H Dose Confirmation Scheme for TSR-042, TSR-022, and 
CarboplatinNab-Paclitaxel Combination Treatment ..............................................103 
Figure 10: Part I Dose Confirmation Scheme for TSR-042, TSR-022, and Carboplatin-
Paclitaxel Combination Treatment ...........................................................................105 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 55 of 259 
 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
ADA 
anti-drug antibody 
ADL 
activities of daily living 
ADP 
adenosine diphosphate 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
alt-NHEJ 
alternative nonhomologous end joining 
AML 
acute myeloid leukemia 
aPTT 
activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase 
ATM 
ataxia telangiectasia mutated 
ATP 
adenosine triphosphate 
AUC 
area under the plasma or serum concentration-time curve 
AUCss 
area under the plasma or serum concentration-time curve at steady state 
BER 
base excision repair 
BIW 
twice weekly 
BP 
blood pressure 
BRCA 
breast cancer gene 
BRCA1 
breast cancer 1 
BRCA2 
breast cancer 2 
BRCA1/2 
breast cancer 1 and breast cancer 2 
BRCAmut 
BRCA mutation 
CA-125 
cancer antigen 125 
CBC 
complete blood count 
CD 
cluster of differentiation 
CD8 T 
CD8+ T cytotoxic 1 
CHK 
check point kinases 
CI 
confidence interval 
CL 
clearance after intravenous administration 
CL/F 
clearance after oral administration 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 56 of 259 
 
Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
Cmax 
maximum observed plasma or serum concentration 
Cmax,ss 
maximum observed plasma or serum concentration at steady state 
Cmin 
minimum observed plasma or serum concentration 
Cmin,ss 
minimum observed plasma or serum concentration at steady state 
CR 
complete response 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
CYP 
cytochrome P450 
DCR 
disease control rate 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
EC50 
50% maximum effective concentration 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
ELISA 
enzyme-linked immunosorbent assay 
EMEA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin embedded 
FT3 
free triiodothyronine 
FT4 
free thyroxine 
GARFT 
glycinamide ribonucleotide formyltransferase 
gBRCAmut 
germline BRCA mutation 
GCP 
Good Clinical Practice 
GCSF 
granulocyte colony-stimulating factor 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
HRDneg 
HRD negative 
HRDpos 
HRD positive 
IB 
Investigator’s Brochure 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 57 of 259 
 
Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
IC50 
50% maximum inhibitory concentration  
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Independent Review Board 
IFN-γ 
interferon gamma 
Ig 
immunoglobulin 
IL-2 
interleukin-2 
IP 
intraperitoneal(ly) 
ITSM 
tyrosine-based switch motif 
IV 
intravenous 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MLR 
mixed lymphocyte reaction 
MRI 
magnetic resonance imaging 
NCCN 
National Comprehensive Cancer Network 
NHEJ 
nonhomologous end joining 
NSCLC 
non-small cell lung cancer 
ORR 
objective response rate 
PARP 
poly(ADP-ribose) polymerase 
PARP1 
poly(ADP-ribose) polymerase 1 
PARP2 
poly(ADP-ribose) polymerase 2 
PD 
progressive disease 
PD-1 
programmed death-1 
PD-L1 
programmed death-ligand 1 
PD-L2 
programmed death-ligand 2 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PO 
orally 
PR 
partial response 
PT 
prothrombin time 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 58 of 259 
 
Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
PTT 
partial thromboplastin time 
Q2W 
every 2 weeks 
Q3W 
every 3 weeks 
Q6W 
every 6 weeks 
QD 
once daily 
QTc 
corrected QT interval 
QTcF 
corrected QT interval calculated using Fridericia’s formula 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RECIST v1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease 
SOC 
system organ class 
SUSAR 
suspected unexpected serious adverse reaction 
T3 
triiodothyronine 
TEAE 
treatment-emergent adverse event 
Th1 
T helper 1  
TIL 
tumor-infiltrating lymphocytes  
TIM-3 
T-cell immunoglobulin and mucin containing protein-3  
TNFα 
tumor necrosis factor alpha 
TS 
thymidylate synthase 
TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 
Vz 
volume of distribution after intravenous administration 
Vz/F 
volume of distribution after oral administration 
WHO 
World Health Organization 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 59 of 259 
 
4. 
INTRODUCTION 
4.1. 
Background 
4.1.1. 
PARP and Homologous Recombination Deficiency 
Poly(ADP-ribose) polymerase (PARP)1 and PARP2 are zinc-finger deoxyribonucleic acid 
(DNA)-binding enzymes that play a crucial role in DNA repair.1 Upon formation of DNA 
breaks, PARP binds at the end of broken DNA strands, a process that activates its enzymatic 
activity. 
Activated PARP catalyzes the addition of long polymers of adenosine diphosphate (ADP)-ribose 
onto PARP and several other proteins associated with chromatin, including histones and various 
DNA repair proteins.2,3 This results in chromatin relaxation, fast recruitment of DNA repair 
proteins, and efficient repair of DNA breaks. In this manner, PARP plays a key role in sensing 
DNA damage and converting it into intracellular signals that activate the base excision repair 
(BER) and single-strand break repair pathways. Normal cells repair up to 10,000 DNA defects 
daily, and single-strand breaks are the most common form of DNA damage. Cells that are unable 
to repair this burden of DNA damage, such as those with defects in the homologous 
recombination or BER pathways, are at risk for accumulating multiple lesions that will 
ultimately trigger apoptosis. They enter the S phase (DNA replication) of the cell cycle with 
unrepaired single- and double-strand breaks. Pre-existing single-strand breaks are converted to 
double-strand breaks as the replication machinery passes. Accumulated double-strand breaks 
present during S phase are repaired by homologous recombination. Homologous recombination 
is the preferred repair pathway because it is associated with a much lower error rate than other 
forms of repair. Cells that are unable to perform DNA repair via homologous recombination 
(e.g., due to inactivation of genes required for homologous recombination, such as breast cancer 
[BRCA1]- or breast cancer 2 [BRCA2]-mutated cells) are at risk for accumulating multiple 
lesions that will ultimately trigger apoptosis. These cells accumulate stalled replication forks 
during S phase and are more likely to use the error-prone nonhomologous end joining (NHEJ) or 
alternative (alt)-NHEJ pathways to repair double-strand breaks in DNA. Accumulation of errors 
in DNA by NHEJ contributes to mutation burden that promotes the development of cancer. Over 
time, the buildup of excessive DNA errors in combination with the inability to complete S phase 
(because of stalled replication forks) contributes to cell death.2,3 
Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset 
of cancer cells with deficiencies in DNA repair pathways. For example, a tumor arising in a 
patient with a germline BRCA mutation (gBRCAmut) has a defective homologous recombination 
DNA repair pathway and would be increasingly dependent on NHEJ, alt-NHEJ, and BER for 
maintenance of genomic integrity. PARP inhibitors block alt-NHEJ and BER, forcing tumors 
with BRCA deficiencies to use the error-prone NHEJ to fix double-strand breaks.1 Non-BRCA 
deficiencies in homologous recombination DNA repair genes could also enhance tumor cell 
sensitivity to PARP inhibitors.4 The rationale for anticancer activity in a subset of 
non-gBRCAmut tumors is that they share distinctive DNA repair defects with gBRCAmut 
carriers, a phenomenon broadly described as “BRCAness.”5 DNA repair defects can be caused 
by germline or somatic alterations to the homologous recombination DNA repair pathway. In a 
recent analysis of approximately 500 high-grade serous ovarian adenocarcinoma tumors, 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 60 of 259 
 
approximately 50% contained homologous recombination defects.6 A subset of these tumors had 
biologically plausible molecular alterations that may make them sensitive to PARP inhibition by 
niraparib. A similar analysis of triple-negative breast cancer indicates that 43% to 44% of these 
patients have tumors with homologous recombination defects.7 Homologous recombination is a 
complex pathway, and several genes other than BRCA1 and BRCA2 are required either to sense 
or repair DNA double-strand breaks via the homologous recombination pathway. Therefore, 
PARP inhibitors are also selectively cytotoxic for cancer cells with deficiencies in DNA repair 
proteins other than BRCA1 and BRCA2.1,5,8  
Recent clinical studies have shown PARP inhibitors to be active in breast and ovarian cancer. 
Clinical anticancer activity with PARP inhibitors has been seen in both patients with gBRCAmut 
and without gBRCAmut; however, activity is more robust in patients with the germline 
mutation.1,4,9-15 In summary, treatment with PARP1/2 inhibitors represents a novel opportunity to 
selectively kill a subset of cancer cell types by exploiting their deficiencies in DNA repair. 
Human cancers exhibit genomic instability and an increased mutation rate due to underlying 
defects in DNA repair. These deficiencies render cancer cells more dependent on the remaining 
DNA repair pathways, and targeting these pathways is expected to have a much greater impact 
on the survival of the tumor cells than that of normal cells. 
4.1.2. 
Immune Surveillance and PD-1 Inhibitors 
The importance of intact immune surveillance in controlling outgrowth of neoplastic 
transformation has been known for decades.16 Accumulating evidence shows a correlation 
between tumor-infiltrating lymphocytes in cancer tissue and prognosis in various 
malignancies.17-29 In particular, the presence of cluster of differentiation (CD)8+ T cells and the 
ratio of CD8+ effector T cells/FoxP3+ regulatory T cells seem to correlate with improved 
prognosis and long-term survival in many solid tumors.25,30-36 The programmed death-1 (PD-1) 
receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control.37 
The normal function of PD-1, expressed on the cell surface of activated T cells under healthy 
conditions, is to down-modulate unwanted or excessive immune responses, including 
autoimmune reactions. PD-1 (encoded by the gene Pdcd1) is an immunoglobulin (Ig) 
superfamily member related to CD28 and cytotoxic T-lymphocyte-associated protein 4 
(CTLA-4), which has been shown to negatively regulate antigen receptor signaling upon 
engagement of its ligands (programmed death-ligand 1 [PD-L1] and programmed death-ligand 2 
[PD-L2]). The structures of murine PD-1 alone38 and in complex with its ligands were the first to 
be resolved,39,40 and more recently the nuclear magnetic resonance-based structure of the human 
PD-1 extracellular region and analyses of its interactions with its ligands were also reported.41 
PD-1 and family members are Type I transmembrane glycoproteins containing an 
Ig variable-type (V-type) domain responsible for ligand binding and a cytoplasmic tail, which is 
responsible for the binding of signaling molecules. The cytoplasmic tail of PD-1 contains 
2 tyrosine-based signaling motifs, an immunoreceptor tyrosine-based inhibition motif, and an 
immunoreceptor tyrosine-based switch motif (ITSM). Following T cell stimulation, PD-1 
recruits the tyrosine phosphatases SHP-1 and SHP-2 to the ITSM within its cytoplasmic tail, 
leading to the dephosphorylation of effector molecules, such as CD3ζ, PKCθ, and ZAP70, which 
are involved in the CD3 T cell signaling cascade.42 The mechanism by which PD-1 
down-modulates T cell responses is similar to, but distinct from, that of CTLA-4.43 PD-1 was 
shown to be expressed on activated lymphocytes, including peripheral CD4+ and CD8+ T cells, 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 61 of 259 
 
B cells, T regs, and natural killer cells.44 Expression has also been shown during thymic 
development on CD4-/CD8- (double-negative) T cells,45 as well as subsets of macrophages46 and 
dendritic cells.47 The ligands for PD-1 (PD-L1 and PD-L2) are constitutively expressed or can be 
induced in a variety of cell types.48 PD-L1 is expressed at low levels on various 
nonhematopoietic tissues, most notably on vascular endothelium, whereas PD-L2 protein is 
predominantly expressed on antigen-presenting cells found in lymphoid tissue or chronic 
inflammatory environments.48 Both ligands are Type I transmembrane receptors containing both 
IgV- and IgC-like domains in the extracellular region and short cytoplasmic regions with no 
known signaling motifs. Binding of either PD-1 ligand to PD-1 inhibits T cell activation 
triggered through the T cell receptor. PD-L2 is thought to control immune T cell activation in 
lymphoid organs, whereas PD-L1 serves to dampen unwarranted T cell function in peripheral 
tissues. Although healthy organs express little (if any) PD-L1, a variety of cancers were 
demonstrated to express abundant levels of this T cell inhibitor,49,50 which, via its interaction 
with the PD-1 receptor on tumor-specific T cells, plays a critical role in immune evasion by 
tumors.51 As a consequence, the PD-1/PD-L1 pathway is an attractive target for therapeutic 
intervention in cancer.52 
4.1.3. 
Anti-TIM-3 Monoclonal Antibody 
In addition to PD-1, another immune protein that has been shown to mediate T-cell exhaustion is 
T-cell immunoglobulin and mucin containing protein-3 (TIM-3). TIM-3 was initially identified 
as a protein selectively expressed on interferon gamma (IFN- producing CD4+ T helper 1 
(Th1) and CD8+ T cytotoxic 1 (CD8 T) cells.53 Early studies demonstrated blockade of TIM-3-
enhanced Th1 cell proliferation and release of IFN-γ and interleukin-2 (IL-2).53 These findings 
supported exploration of targeting TIM-3 for tumor immunotherapy. A role for TIM-3 in 
mediating T-cell exhaustion in cancer has been suggested in multiple preclinical murine models 
showing expression of TIM-3 and PD-1 on tumor-infiltrating lymphocytes (TILs).54-56 The 
therapeutic efficacy of targeting these proteins demonstrated limited tumor control with TIM-3 
or PD-1 blockade alone but enhanced immune-mediated control of tumor growth with concurrent 
TIM-3 and PD-1 blockade. These data demonstrate the expression of TIM-3 and PD-1 on TILs 
and implicated TIM-3 and PD-1 in limiting T-cell effector function in the tumor 
microenvironment.  
Similar to the effects observed in murine models, TIM-3 expression on TILs in human tumors 
has also been shown to mediate immunosuppression. A wide variety of tumor types are 
infiltrated by CD8 T cells and these CD8 T cells express TIM-3 and PD-1 among other 
immunosuppressive proteins such as lymphocyte-activation gene-3 and CTLA-4.57-59 
Intriguingly, the presence of TIM-3+ T cells was increased in patients with non-small cell lung 
cancer (NSCLC) with more advanced disease. Additional studies have reported the expression of 
TIM-3 on tumor infiltrating regulatory T cells that correlates with enhanced immunosuppressive 
properties of these cells in an ex vivo assay.60 In patients with melanoma, characterization of 
TIM-3 expression on CD8 T cells specific for a tumor antigen revealed that co-expression of 
TIM-3 and PD-1 marks TILs with the lowest proliferative potential that also fails to produce IL-
2, tumor necrosis factor α (TNF, and IFN61 Building on this phenotypic characterization of 
TIM-3 expression, the function of CD8 T cells from these patients that co-express TIM-3 and 
PD-1 demonstrate suppressed secretion of IFN, TNF, and IL-2 following ex vivo stimulation 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 62 of 259 
 
that can be improved via blockade of both TIM-3 and PD-1.61 In addition to a role on CD8 T 
cells, regulatory T cells that suppress T-cell function can express TIM-3 and are enriched within 
the tumor microenvironment in human tumors and murine models. These TIM 3+ regulatory T 
cells exhibit superior suppressive capability relative to TIM-3-negative regulatory T cells 
resulting in limited CD8 T cell-mediated anti-tumor immunity.60,62 Thus, the expression and 
function of TIM-3-expressing T cells in the tumor microenvironment in humans largely reflects 
the data generated in murine models and supports the exploration of TIM-3 blockade as a 
strategy to enhance anti-tumor immunity. The possibility of enhancing the clinical activity of 
tumor immunotherapy through TIM-3 blockade supports the value of developing an antibody 
that targets TIM-3 to utilize as monotherapy and in combination with other therapeutic 
approaches. TSR-022 is an IgG4-k isotype humanized monoclonal antibody that binds with high 
affinity to TIM-3. This antibody was generated based on a proprietary platform that utilizes 
affinity maturation to select antibodies with desired functional characteristics. Details on the 
nonclinical and clinical experience with TSR-022 are presented in Section 4.2.3. 
Based on the preclinical data identifying TIM-3 expression on tumor infiltrating T cells in a 
broad range of tumors and TIM-3 blockade resulting in enhanced T-cell activity, TSR-022 is 
expected to result in clinical activity in patients with a variety of tumors and thus TSR-022 is 
being advanced for clinical development as an immunotherapy for advanced malignancies. To 
date, 46 patients have been treated with TSR-022 monotherapy, and 142 patients have been 
treated with TSR-022+TSR-042 combination therapy at 500 mg TSR-042 and 100, 300, or 
900 mg TSR-022. 
Please refer to the current TSR-022 Investigator’s Brochure (IB) for additional information. 
4.1.4. 
Carboplatin-Paclitaxel Chemotherapy 
The main target of carboplatin is DNA, to which it binds efficiently, thereby inhibiting 
replication and transcription and inducing cell death.63 Thrombocytopenia is chief among the 
potential side effects of carboplatin. To avoid severe thrombocytopenia, Calvert’s formula is 
recommended in calculating the intravenous (IV) dose of carboplatin to be administered.64  
Paclitaxel promotes tubulin polymerization, causing cell death by disrupting the normal 
microtubule dynamics required for cell division and vital interphase processes. Paclitaxel has 
shown activity against a broad range of tumor types, including breast, ovarian, lung, and head 
and neck cancers.65  
Carboplatin in combination with paclitaxel has been shown to be efficacious against a variety of 
different tumor types, including NSCLC, ovarian cancer, endometrial cancer, and head and neck 
cancer.66-69 Additional information on carboplatin and paclitaxel can be found in the prescribing 
information for each.  
4.1.5. 
Carboplatin-Pemetrexed Chemotherapy 
Pemetrexed is a folate analog metabolic inhibitor that exerts its action by disrupting folate-
dependent metabolic processes essential for cell replication. In vitro studies have shown that 
pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide 
ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the 
de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 63 of 259 
 
membrane carriers such as the reduced folate carrier and membrane folate binding protein 
transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the 
enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are 
inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process 
that occurs in tumor cells and is thought to occur, to a lesser extent, in normal tissues. 
Polyglutamated metabolites are thought to have an increased intracellular half-life, resulting in 
prolonged drug action in malignant cells.70 
Pemetrexed combined with cisplatin has been proven efficacious in a first-line setting for non-
squamous NSCLC71, and single-agent maintenance therapy with pemetrexed improved 
progression-free survival (PFS) and overall survival after induction therapy with a 
nonpemetrexed platinum doublet.72 In addition, patients with advanced non-squamous NSCLC 
who continued single-agent pemetrexed maintenance therapy after induction therapy with 
pemetrexed-cisplatin showed a significant improvement in PFS compared with those who 
received placebo maintenance therapy after the same induction therapy.73  
4.1.6. 
Carboplatin–Nab-Paclitaxel Chemotherapy 
Nab-paclitaxel is a 130-nm albumin-bound formulation of paclitaxel that is indicated for locally 
advanced or metastatic NSCLC, as first-line treatment in combination with carboplatin in 
patients who are not candidates for curative surgery or radiation therapy.74,75 It is suggested that 
nab-paclitaxel may reach the tumor microenvironment more efficiently than solvent-based 
paclitaxel via caveolae-mediated transcytosis and may be preferentially taken up by cancer 
cells.75 Because of its saline medium, nab-paclitaxel can be administered safely at higher doses 
and for shorter durations without the need for the corticosteroid and antihistamine premedication 
that is needed to prevent solvent-related hypersensitivity reactions seen with solvent-based 
paclitaxel.76,77 Nab-paclitaxel has shown increased ORR and time to progression in metastatic 
breast cancer compared with solvent-based paclitaxel78 and has shown antitumor activity and 
improved ORR compared with solvent-based paclitaxel as first-line therapy in patients with 
NSCLC.79,80 
4.1.7. 
Bevacizumab 
Bevacizumab is an antiangiogenic recombinant humanized monoclonal immunoglobulin G1 
antibody against the vascular endothelial growth factor (VEGF) protein. Bevacizumab (Avastin; 
Genentech/Roche US) has been approved in the US and European Union (EU) for the treatment 
of multiple tumor types in combination with certain other treatments. In the EU, bevacizumab is 
approved for the front-line treatment of adult patients with advanced (International Federation of 
Gynecology and Obstetrics [FIGO] Stages IIIB, IIIC, and IV) ovarian cancer. In the US, 
bevacizumab is approved for the treatment of patients with platinum-sensitive recurrent ovarian 
cancer, either in combination with carboplatin and paclitaxel or in combination with carboplatin 
and gemcitabine, followed by bevacizumab as a single agent.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 64 of 259 
 
4.2. 
Study Treatments 
4.2.1. 
Niraparib 
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment 
for patients with tumors that harbor defects in the homologous recombination DNA repair 
pathway or that are driven by PARP-mediated transcription factors. 
4.2.1.1. 
Nonclinical Experience 
Nonclinical data on niraparib are discussed in detail in the niraparib IB. Briefly, in nonclinical 
models, niraparib has been observed to inhibit normal DNA repair mechanisms and induce 
synthetic lethality when administered to cells with homologous recombination defects. In a 
BRCA1-mutant xenograft study, niraparib dosed orally caused tumor regression, which was 
mirrored by a >90% reduction in tumor weight compared with control. In a BRCA2-mutant 
xenograft study, niraparib-dosed mice showed 55% to 60% growth inhibition, both by tumor 
volume and weight. 
Niraparib displayed strong antitumor activity in in vivo studies with BRCA1-mutant breast 
cancer (MDA-MB-436), BRCA2-mutant pancreatic cancer (CAPAN-1), and with patient-derived 
Ewing sarcoma mice models. Utilizing patient-derived ovarian and breast cancer xenograft 
models, niraparib demonstrated response in both BRCAmut and BRCA wild-type tumors. 
4.2.1.2. 
Clinical Experience 
Niraparib clinical data are discussed in detail in the niraparib IB. In the Phase 1 clinical program, 
niraparib, as a monotherapy or in combination with chemotherapy, has been administered to 
144 patients. 
Phase 1 Study of Niraparib Monotherapy in Advanced Solid Tumors 
Clinical activity data for niraparib administered as monotherapy in patients with ovarian cancer 
are available from 1 early-phase clinical study. In Parts A and B of the Phase 1 study PN001 
(ClinicalTrials.gov identifiers: MK-4827-001 and 2008_501), 100 patients with advanced solid 
tumors who had received a median of 3 prior therapies were enrolled; 49 patients had ovarian 
cancer (13 platinum-sensitive, 35 platinum-resistant, and 1 platinum-refractory).11 An additional 
4 patients were enrolled in Part D of the study, which assessed pharmacokinetics only.81  
The most common nonhematological TEAEs were nausea, fatigue, anorexia, constipation, 
vomiting, and insomnia. These TEAEs were mainly mild to moderate in severity, self-limiting, 
and manageable with standard treatments. Hematological toxicity appeared to be dose 
proportional and most frequently arose in the setting of cumulative doses. Anemia was reported 
in 48 (48%) of 100 patients and was Grade ≥3 in 10 (10%) of 100 patients. Thrombocytopenia 
was less common (35 [35%] of 100 patients) and was Grade ≥3 in 15 (15%) of 100 patients. 
Neutropenia was the least commonly reported (24 [24%] of 100 patients), and was Grade 3 in 
4 (4%) of 100 patients at niraparib doses of 300 and 400 mg. In all cases, hematological TEAEs 
were uncomplicated and reversible. Twenty patients required dose reductions (usually by 1 dose 
level) for recurrent anemia or thrombocytopenia. Treatment was discontinued due to AEs in 
7 patients, including the 4 patients who had DLTs during the first cycle and 3 patients who had 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 65 of 259 
 
Grade 3 vomiting, Grade 2 prolongation of QT interval, and Grade 3 prolongation of QT 
interval. No treatment-related deaths occurred. 
Of the 49 patients, 22 had confirmed BRCA1 or BRCA2 mutation, of whom 20 were 
radiologically assessable. Eight (40%) of these 20 patients achieved a confirmed partial response 
(PR) by Response Evaluation Criteria in Solid Tumors (RECIST) and cancer antigen 125 
(CA-125) Gynecologic Cancer Intergroup criteria at doses ranging from 80 to 400 mg per day. 
Median response duration was 387 days (range: 159 to 518 days). Three (33%) of 9 patients with 
platinum-resistant BRCAmut ovarian cancer had PR by RECIST and CA-125 criteria. In patients 
with platinum-sensitive disease, 5 (50%) of 10 patients (95% CI: 19 to 81) with BRCA1 or 
BRCA2 mutations had RECIST and CA-125 responses. 
Phase 3 Study of Niraparib Monotherapy in Platinum-sensitive, Recurrent Ovarian Cancer 
The selection of the 300 mg starting dose of niraparib for the NOVA study was based on data 
from the MSD-conducted Phase 1 MAD study PN001. There were no formal Phase 2 dose-
ranging studies conducted. The Phase 1 study included both a dose escalation phase to determine 
the MTD and an expansion arm to further evaluate the selected dose. A total of 104 patients with 
advanced solid tumors were evaluated in this study, including 60 during dose escalation from 30 
mg to 400 mg and 54 during expansion at the 300 mg dose level. The dose escalation stage 
determined that 400 mg exceeded the MTD (by traditional dose-limiting toxicity [DLT] 
evaluations and by using the pooled adjacent violators algorithm). No DLTs were observed at 
290 or 300 mg dose levels.  
In a Phase 3 study, niraparib was compared to placebo in 546 patients with platinum-sensitive 
recurrent ovarian cancer who had received at least 2 previous chemotherapy regimens and 
niraparib or placebo maintenance (“NOVA” study). In this pivotal study, daily niraparib 
improved progression-free survival (PFS) in a cohort of patients with gBRCA mutation as well as 
in a cohort of patients without gBRCA mutation. Within the gBRCAmut cohort, the median PFS 
was 21.0 months in patients on niraparib versus 5.5 months on placebo (hazard ratio [HR], 0.27; 
p < 0.0001). In recurrent ovarian cancer patients, efficacy was assessed in patients with 
HRD-positive tumors as identified by the Myriad’s myChoice HRD test as well in the overall 
non-gBRCA mutation cohort regardless of HRD status. As observed in the gBRCAmut cohort, 
PFS was significantly longer with niraparib in the homologous recombination deficient-positive 
group of the non-gBRCAmut (without germline BRCA mutation) cohort (median, 12.9 months vs 
3.8 months; HR, 0.38; p < 0.0001). Lastly, PFS was significantly improved in the overall non-
gBRCAmut cohort (median, 9.3 months vs 3.9 months; HR, 0.45; p < 0.0001). Secondary 
endpoints, including chemotherapy-free interval, time to first subsequent therapy (TFST), and 
progression-free survival 2 (PFS2), confirmed the PFS benefit of niraparib treatment in both 
cohorts. This provides compelling evidence that niraparib does not diminish responsiveness to 
subsequent therapy and that the niraparib treatment effect persists. Subsequently in 2017, a 
recommendation to consider niraparib maintenance therapy in this setting in cases of CR and PR 
was added to the National Comprehensive Cancer Network (NCCN) guidelines.7  
In the NOVA study, the most commonly observed non-hematologic treatment-emergent adverse 
events (TEAEs) of any National Cancer Institute - Common Terminology Criteria for Adverse 
Events (NCI-CTCAE) grade were nausea, fatigue, constipation, and vomiting; the majority of 
the non-hematologic TEAEs were mild to moderate in severity. The most commonly observed 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 66 of 259 
 
hematologic TEAEs (any grade) were anemia (48.5%), thrombocytopenia 66.2%), and 
neutropenia (31.4%). The incidence of myelodysplastic syndrome (MDS) and/or acute myeloid 
leukemia (AML) in patients who received niraparib in the NOVA study was similar to that in 
patients who received placebo (1.4% and 1.0%, respectively). MDS/AML and secondary cancers 
(new malignancies other than MDS or AML) are potential risks of PARP inhibitors. Guidance on 
monitoring patients for new AEs of MDS/AML and the follow-up of patients with suspected 
MDS/AML is provided in Section 10.6.7.  
TEAE’s leading to treatment interruption, reduction or discontinuation were 68.9%, 66.5% and 
14.7% respectively. Approximately 50% of patients required dose interruption during the first 
month of niraparib therapy, and 47% required dose reduction during the second month of 
therapy. Most patient achieved their individual maximal tolerated dose by the third month. The 
average dose of niraparib during the study was 206 mg. After Month 3 or 4, new incident 
thrombocytopenia was reported in < 1% of patients. Although Grade 3 or 4 hematologic 
laboratory events were common at the initiation of treatment, no severe clinical sequelae were 
observed, and relatively few patients discontinued due to these AEs (discontinuation rate was 
3.3% for thrombocytopenia, 1.4% for anemia and 1.9% for neutropenia). Dose adjustment based 
on individual tolerability during the first 3 cycles substantially reduced the incidence of these 
events beyond Cycle 3.  
Baseline Platelet Count and Weight as Predictors of Thrombocytopenia. 
An analysis was conducted using the data collected in ENGOT-OV16/NOVA and the initial 
phase I study, PN001. This analysis determined that only baseline platelets had an impact on 
platelet nadir; lower baseline platelets (<180 109/L) were associated with an increased frequency 
of thrombocytopenia Grade ≥1 (76%) or Grade ≥ 3 (45%) compared to patients with higher 
baseline platelet counts. Further, an exploratory analysis of clinical data versus baseline body 
weight from ENGOT-OV16/NOVA was conducted.  For this analysis, the weight categories 
were based on quartiles with the lowest quartile (patients with a body weight less than 58 kg at 
baseline) compared to the highest quartile (patients with a body weight greater than or equal to 
77 kg at baseline).  While TEAEs occurred in most patients regardless of body weight, Grade ≥3 
TEAEs, SAEs, and TEAEs leading to dose modification or treatment discontinuation occurred 
more commonly in the weight <58 kg cohort than in the ≥77 kg cohort. In the cohort of patients 
with a body weight <58 kg, approximately 80% of patients had a dose reduction compared to 
59% of patients with a weight greater than or equal to 77 kg. Treatment discontinuations were 
increased in the patients with lower body weight (24%) compared to patients in the highest 
quartile (10%). 
The potential relationship between body weight and TEAEs was further explored in an analysis 
to evaluate the correlation of grade 3 or 4 thrombocytopenia and baseline body weight.  The 
lowest platelet count in the first 30 days was plotted versus baseline body weight to determine if 
low body weight identified a subgroup of patients with higher levels of thrombocytopenia during 
Cycle 1.  In the first 30 days of treatment, a baseline body weight >77 kg is associated with a 
lower incidence of grade 3 or 4 thrombocytopenia (14%) relative to the group with body weight 
<58 kg (43%).  
Finally, a classification tree approach was used to refine the best cut-off points for predicting the 
likelihood of a patient developing ≥Grade 3 thrombocytopenia within 30 days after the first dose 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 67 of 259 
 
of niraparib.  The results of the model show that the subgroup of patients with a baseline body 
weight <77 kg or baseline platelet count <150,000 µL had a grade 3/4 thrombocytopenia rate in 
the first 30 days of 35.4% compared to 11.5% in the group of patients with a body weight >77 kg 
and a platelet count >150,000 µL. Further, the average daily dose was 258 mg through the first 
two cycles for patients with a body weight >77 kg and platelet count >150,000 µL, and was only 
206 mg for patients with body weight < 77 kg or platelet count <150,000 µL. Thus, the actual 
delivered dose approximated a starting dose of 200 mg despite the intended delivery of a starting 
dose of 300 mg. These observations are to be confirmed in the present study with the inclusion of 
study treatment dosed at 200 mg (2 capsules of niraparib or placebo) in patients whose baseline 
weight is <77 kg or baseline platelet count is <150,000 µL. 
Study PR-30-5011-C1 (NOVA corrected QT interval [QTc] substudy; n = 26) was an open-label 
evaluation of the effects of niraparib on QTc measurements in patients with histologically 
diagnosed ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. There were no 
reports of clinically significant abnormal electrocardiogram (ECG) changes, including QTc 
interval prolongation, attributed to niraparib. Administration of niraparib at the therapeutic dose 
did not prolong the QT interval. There was no correlation between the exposure level (i.e., 
plasma concentration) of niraparib and QTc changes (i.e., change in corrected QT interval 
calculated using Fridericia’s formula [ΔQTcF]).  
4.2.2. 
TSR-042 
TSR-042 is an IgG4 humanized monoclonal antibody that binds with high affinity to PD-1, 
resulting in inhibition of binding to PD-L1 and PD-L2. This antibody was generated based on a 
proprietary platform that utilizes affinity maturation to select highly-specific antibodies with 
desired functional characteristics. The functional antagonist activity of TSR-042 was confirmed 
in a mixed lymphocyte reaction assay, demonstrating enhanced interleukin-2 (IL-2) production 
upon addition of TSR-042. Furthermore, TSR-042 has an acceptable safety profile based on 
toxicology studies in cynomolgus monkeys. Additional information on the nonclinical and 
clinical experience with TSR-042 can be found in the TSR-042 IB. 
4.2.2.1. 
Nonclinical Experience 
TSR-042 binds with high affinity to human and cynomolgus monkey PD-1. TSR-042 blocks 
binding of soluble ligands to human PD-1 expressed on the surface of Chinese hamster ovary 
cells, with a 50% maximum inhibitory concentration (IC50) of approximately 1 nM. TSR-042 
enhances T cell activation, as measured by the production of IL-2 from activated CD4+ T cells, 
with a 50% maximum effective concentration (EC50) of approximately 1 nM. Full PD-1 receptor 
occupancy achieved by TSR-042 in human and cynomolgus monkey T cells from peripheral 
blood mononuclear cells was determined to occur at concentrations of approximately 1 μg/mL. 
Linear pharmacokinetic (PK) was observed for TSR-042 over the dose range tested of 10 to 
100 mg/kg. Sex had no effect on exposure. The volume of distribution at steady state was low 
and suggested minimal tissue penetration, which is commonly observed for therapeutic 
monoclonal antibodies. Weekly administration resulted in approximately 2- to 3-fold increase in 
TSR-042 exposure. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 68 of 259 
 
The safety of TSR-042 was characterized in a single-dose, a 4-week repeat-dose (5 doses), and a 
13-week repeat-dose (14 doses) toxicity study in cynomolgus monkeys when administered as IV 
doses of 10, 30, or 100 mg/kg. In the repeat-dose studies, the dose frequency was once a week. 
TSR-042 was well tolerated in cynomolgus monkeys, with a systemic exposure (AUC0-168h) of 
up to approximately 419,000 h × μg/mL over the course of the 4-week repeat-dose study. No 
findings of toxicological significance were observed in either single-dose or 4-week repeat-dose 
toxicity study with TSR-042, and the no observed adverse effect level (NOAEL) was 
≥ 100 mg/kg. In addition, no findings of toxicological relevance were observed in the in vitro 
tissue cross-reactivity study using human and cynomolgus monkey tissues.   
In the 13-week repeat-dose toxicity study, microscopic findings of an immune-mediated nature 
were observed in animals dosed with TSR-042 at ≥ 10 mg/kg/week. Additionally, 1 male dosed 
at 10 mg/kg/week was euthanized because of chronic, unresolved generalized skin findings. 
Microscopic findings in the skin of this animal were indicative of an immune reaction. 
Considering the mechanism of action of TSR-042, these findings could be the results of a 
pharmacological effect of TSR-042. Because of the euthanasia of 1 male in the 10 mg/kg dose 
group, the NOAEL could not be determined in this study. 
4.2.2.2. 
Clinical Experience 
As of 21 January 2018, there were 4 ongoing Phase 1 studies with TSR-042: Study 4010-01-001 
(TSR-042 monotherapy), Study 4020-01-001 (TSR-042 combination therapy), 
Study 3000-01-002 (TSR-042 combination therapy), and Study 4040-01-001 (TSR-042 
combination therapy).  
Study 4010-01-001 is an ongoing first-in-human Phase 1 study of TSR-042 to evaluate the safety 
and tolerability, PK, pharmacodynamics, and clinical activity of TSR-042 in patients with 
recurrent or advanced solid tumors. The study is being conducted in 2 parts: 
 Part 1 (dose escalation) of the study used a modified 3 + 3 design to evaluate 
3 ascending weight-based doses of TSR-042 as follows: 1, 3, and 10 mg/kg 
administered every 2 weeks (Q2W) via IV infusion.  
 Part 2 of the study is being conducted in 2 subparts (Part 2A and Part 2B) to explore 
the safety and clinical activity of TSR-042 administered as a fixed dose (i.e., not 
weight based). 
 In Part 2A, following the completion of Part 1, the safety and tolerability of 
TSR-042 was evaluated at fixed doses of 500 mg every 3 weeks (Q3W) and 1,000 
mg every 6 weeks (Q6W) using a modified 6 + 6 design.  
 In Part 2B, the clinical activity, tolerability, and safety of TSR-042 at the 
recommended phase 2 dose (RP2D) are being evaluated in patients with specific 
tumor types.  
Dose escalation in Part 1 of the study continued to a maximally administered dose of 10 mg/kg 
Q2W, and a maximum tolerated dose was not identified. No dose-limiting toxicities (DLTs) 
were observed. Following completion of Part 1, Part 2A evaluated safety and tolerability of 
TSR-042 at 2 fixed dosing schedules of 500 mg Q3W and 1,000 mg Q6W. No DLTs were 
observed in Part 2A. Based on the PK/pharmacodynamic profile and safety and tolerability data 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 69 of 259 
 
from the dose regimens evaluated in Part 1 and Part 2A, the RP2D was determined to be 500 mg 
Q3W for 4 cycles followed by 1,000 mg Q6W thereafter. 
As of 21 January 2018, 135 patients with heavily pretreated advanced solid tumors have been 
treated with TSR-042 in Study 4010-01-001: 21 patients in Part 1 and 114 patients in Parts 2A 
and 2B. The majority of these patients (92.6%) reported at least 1 treatment-emergent adverse 
event (TEAE), with events of fatigue, nausea, and decreased appetite being the most frequently 
reported. Study drug-related TEAEs of Grade ≥ 3 were reported in 13 patients (9.6%). The 
majority of these events occurred in only 1 patient each, with the exception of aspartate 
aminotransferase increased (3 patients), alanine aminotransferase increased (2 patients), and 
fatigue (2 patients). Serious adverse events (SAEs) occurred in 38 patients (28.1%), for 5 of 
these patients the event was considered study drug-related. Eight patients had an adverse event 
(AE) leading to study drug discontinuation. Six patients had an AE leading to study drug 
discontinuation which was considered study drug-related. Three patients had an AE leading to 
death. None of the AEs leading to death were considered to be related to the study drug. 
As of 21 January 2018, a total of 51 patients with heavily pretreated advanced solid tumors have 
been treated with TSR-042 in combination with other therapeutic agents: 28 patients received 
TSR-042 in combination with TSR-022 in Study 4020-01-001, 9 patients received TSR-042 in 
combination with niraparib in Part A of Study 3000-01-002, and 14 patients received TSR-042 in 
combination with carboplatin and paclitaxel in Part B of Study 3000-01-002. The majority 
(80.4%) of patients receiving TSR-042 combination therapy reported at least 1 TEAE, with 
events of fatigue and dyspnoea being the most frequently reported. One DLT (Grade 3 aspartate 
aminotransferase increased) was reported in a patient in Part B of Study 3000-01-002. Serious 
AEs occurred in 14 patients, none of these events were considered study drug-related. 
One patient had at least 1 AE leading to study drug discontinuation (alanine aminotransferase 
increased and aspartate aminotransferase increased). Both events were considered study 
drug-related. No patient had an AE leading to death. 
4.2.3. 
TSR-022 
4.2.3.1. 
Nonclinical Experience 
TSR-022 is an IgG4-κ isotype humanized monoclonal antibody that binds with high affinity to 
TIM-3. Binding of TSR-022 to TIM-3 has been demonstrated in nonclinical assays and is similar 
for human and monkey proteins. Full TIM-3 receptor occupancy was observed ex vivo in human 
peripheral blood mononuclear cells (PBMCs) at a concentration of approximately 0.6 µg/mL. 
TSR-022 is unlikely to independently induce cytokine release, activate the complement system, 
or elicit complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated 
cytotoxicity (ADCC) at clinically relevant doses. TSR-022 augments T cell activity as measured 
by enhanced IL-2 production in multiple assays. This agonist activity is further enhanced by the 
addition of an anti-PD-1 antibody. 
The PK properties of TSR-022 were characterized in cynomolgus monkeys using both single- 
and repeat-dose studies. TSR-022 exhibits kinetics typical of mAbs, with a limited volume of 
distribution and a slow to moderate clearance. Consecutive weekly dosing of 10, 30, and 
100 mg/kg in cynomolgus monkeys showed a moderate accumulation of TSR-022. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 70 of 259 
 
The results from the 2 repeat-dose toxicity studies indicated that weekly administration of 
TSR-022 at doses up to 100 mg/kg for a total of 3 or 5 doses was well tolerated in cynomolgus 
monkeys. No study drug-related findings of toxicological significance were observed in either 
repeat-dose toxicity study, and the NOAEL was ≥100 mg/kg in both studies. ADA formation 
was observed in several animals in both repeat-dose studies but was not associated with any 
toxicity. 
4.2.3.2. 
Clinical Experience  
As of the clinical cutoff date of 19 May 2018, there is 1 ongoing study with TSR-022: 
Study 4020-01-001, a first-in-human study of TSR-022 to evaluate the safety and tolerability, 
PK, pharmacodynamic, immunogenicity, and clinical activity of TSR-022 in patients with 
advanced solid tumors. The study is conducted in 2 parts:  
 Part 1 (dose escalation, safety, and tolerability) of the study is conducted in 3 subparts 
(Part 1a, Part 1b, and Part 1c) to evaluate the safety and tolerability of TSR-022 
monotherapy or combination therapy. All 3 subparts use a 3 + 3 design. 
 In Part 1a, the safety and tolerability of TSR-022 administration Q2W were 
evaluated based on weight (0.03, 0.1, 0.3, 1, 3, or 10 mg/kg doses) or as a fixed 
dose of 1,200 mg. 
 In Part 1b, the safety and tolerability of TSR-022 at 1 mg/kg Q2W in combination 
with nivolumab at 3 mg/kg Q2W were evaluated.  
 In Part 1c, the safety and tolerability of TSR-022 (100, 300, or 900 mg) in 
combination with TSR-042 (500 mg) administered Q3W are being evaluated. 
 Part 2 (antitumor activity) of the study will evaluate the efficacy of TSR-022 as 
monotherapy and in combination with TSR-042.  
As of 19 May 2018, 194 patients in this study have been treated with TSR-022 as monotherapy 
or in combination with nivolumab or TSR-042. Dose escalation in Part 1a of the study continued 
to a maximally administered dose of 1,200 mg Q2W, and a maximum tolerated dose was not 
identified. The majority (95.7%) of the 46 patients who were treated with TSR-022 monotherapy 
in Part 1a reported at least 1 TEAE, with fatigue and nausea being the most frequently reported. 
Grade ≥3 TEAEs considered by the Investigator to be related to study drug were experienced by 
2 patients. For 1 of the 2 patients, the event was considered dose-limiting (Grade 3 lipase 
increased; 10 mg/kg TSR-022). SAEs were reported in 26.1% of patients; only 1 patient (2.2%) 
had an SAE assessed by the Investigator to be related to study drug. Two patients (4.3%) 
discontinued the study drug due to a TEAE, and for 1 patient (2.2%), this was assessed as related 
to study drug by the Investigator. No patient had a TEAE leading to death. 
As of 19 May 2018, a total of 7 patients were treated with TSR-022 in combination with 
nivolumab, and 142 patients were treated with TSR-022 in combination with TSR-042. Because 
2 patients treated with TSR-022 in combination with nivolumab experienced a DLT (Grade 3 
diarrhea [1 patient] and Grade 3 alanine aminotransferase increased with Grade 3 aspartate 
aminotransferase increased [1 patient]), Part 1b of the study was discontinued. All 7 patients who 
were treated with TSR-022 + nivolumab combination therapy reported at least 1 TEAE; 
6 patients (85.7%) experienced TEAEs considered by the Investigator to be related to study drug. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 71 of 259 
 
TEAEs of Grade ≥3 were reported in 6 patients (85.7%), and 2 patients (28.6%) experienced 
Grade ≥3 TEAEs considered by the Investigator to be related to study drug. SAEs were reported 
in 4 patients (57.1%), and no patients had SAEs assessed to be related to study drug by the 
Investigator. Four patients (57.1%) discontinued the study drug due to a TEAE, and for 1 patient 
(14.3%), this was assessed as related to study drug by the Investigator. No patient had a TEAE 
leading to death. 
As of 19 May 2018, the majority (85.2%) of the 142 patients who received TSR-022 in 
combination with TSR-042 experienced TEAEs; 42.3% experienced TEAEs considered by the 
Investigator to be related to study drug. TEAEs of Grade ≥3 were reported in 35.9% of patients, 
and 6.3% experienced Grade ≥3 TEAEs considered by the Investigator to be related to study 
drug. SAEs were reported in 27.5% of patients; 6.3% experienced SAEs considered by the 
Investigator to be related to study drug. Seven patients (4.9%) discontinued study drug due to a 
TEAE; 1 patient (0.7%) experienced a TEAE leading to study drug discontinuation that was 
considered by the Investigator to be related to study drug. Two patients (1.4%) had TEAEs 
leading to death; neither were assessed as related to study drug by the Investigator. 
4.2.4. 
Bevacizumab  
4.2.4.1. 
Clinical Experience 
Bevacizumab has been evaluated in multiple clinical studies, including in 1,873 patients with 
newly diagnosed, Stage III (incompletely resected) or Stage IV epithelial ovarian cancer who had 
undergone debulking surgery as part of a Phase 3 study (GOG218).82 Patients receiving 
bevacizumab administered concurrently with chemotherapy and as a maintenance treatment 
showed statistically significant improvement in PFS compared to placebo (14.1 months vs 
10.3 months; HR, 0.717; p < 0.001).  
Bevacizumab was also evaluated in 1,528 patients with ovarian cancer, regardless of FIGO stage 
as part of a Phase 3 study (ICON7).83 Patients receiving bevacizumab administered concurrently 
with chemotherapy and as a maintenance treatment showed statistically significant improvement 
in PFS compared to chemotherapy alone (19.0 months vs 17.3 months; HR, 0.81; p = 0.004), 
with maximum improvement compared to chemotherapy alone at 12 months (15.1%; 
95% confidence interval [CI], 10.7-19.5). The improvement was even more pronounced in 
patients at high risk of progression (i.e., FIGO Stage IV or FIGO Stage III and >1.0 cm of 
residual disease after debulking surgery; 15.9 months vs 10.5 months; HR, 0.68; p = <0.001). 
4.2.5. 
TSR-042 and Niraparib Combination Treatment 
4.2.5.1. 
Nonclinical Experience 
The efficacy and tolerability of niraparib in combination with anti-PD-1 therapy was evaluated in 
several nonclinical models. The combination was well tolerated in all of these studies. The 
combination was first tested in a homologous recombination-deficient ovarian cancer mouse 
model derived from BRCA null genetic background,84 as PARP inhibition was previously shown 
to increase immune cell infiltration in BRCA-deficient models.85 In a study of a ovarian 
carcinoma mouse model,86 niraparib (50 mg/kg orally [PO] QD) and anti-mPD-1 (5 mg/kg 
intraperitoneally [IP] twice weekly [BIW]) were administered to mice either alone or in 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 72 of 259 
 
combination for 16 days. The combination was tolerated with no treatment-related death. Almost 
all the tumors achieved complete regression upon treatment with niraparib, anti-mPD-1, and the 
combination. Complete regression was first observed on treatment Day 16 in 2 of 6, 1 of 6, and 
4 of 6 mice from the niraparib, anti-mPD-1, and combination groups, respectively. These results 
suggest that the therapeutic approach of combining niraparib with a PD-1 inhibitor such as TSR-
042 may provide additional benefit for patients with homologous recombination-deficient 
tumors.  
Niraparib and anti-PD-1 combination treatment has also been evaluated in several syngeneic 
models representing breast cancer 1 and breast cancer 2 (BRCA1/2) wild-type tumors, one of 
which was the breast cancer mouse model LPA1-T22. In study of a syngeneic transplant breast 
cancer model, niraparib (50 mg/kg PO QD) and anti-PD-1 antibody (10 mg/kg IV BIW) were 
administered to mice either alone or in combination for 15 days. While these tumors were 
moderately responsive to niraparib or anti-PD-1 antibody alone, with average tumor growth 
inhibition of approximately 50% for niraparib and 30% for PD-1 antibody, synergistic anti-tumor 
activity with near-complete tumor growth inhibition (>95%) was achieved with the 
combination.87 In a similar study using the lung squamous syngeneic model KLN205, stronger 
tumor growth inhibition was observed for the combination (52.3%) than for niraparib alone 
(36.7%) or anti-PD-1 alone (30.5%).88 Together, these data support the therapeutic approach of 
combining niraparib with anti PD-1 agent in either BRCA1/2 mutant or wild-type tumors. 
4.2.5.2. 
Clinical Experience 
This study is the first to assess TSR-042 and niraparib combination treatment; therefore, no 
clinical data are currently available for TSR-042 and niraparib combination treatment. 
4.2.6. 
Carboplatin-Paclitaxel in Combination With PD-1 or PD-L1 Antibodies 
4.2.6.1. 
Nonclinical Experience 
There is accumulating evidence that, in addition to direct cytostatic and cytotoxic effects, the 
mechanism of action of conventional chemotherapies may also involve activation of 
tumor-targeted immune responses, including increasing the immunogenicity of cancer cells and 
reducing immunosuppression of tumors.89 In nonclinical models, platinum-based agents have 
been suggested to increase direct cytostatic-mediated activation of T cells by several 
mechanisms, including down-regulation of PD-L2, increased adenosine triphosphate, and 
increased high mobility group protein box-1 release from dying cells.90 Several 
immunostimulatory effects of paclitaxel on the immune system have also been reported; among 
these are the induction of endoplasmic reticulum stress, which can lead to calreticulin exposure 
and dendritic cell stimulation,91 depletion of myeloid-derived suppressor cells,92,93 and boosting 
of T-cell priming.94 These data suggest that chemotherapy agents may modulate the tumor 
microenvironment, an effect that could be enhanced by the addition of immune checkpoint 
inhibitors, such as those targeting PD-1 or PD-L1. 
4.2.6.2. 
Clinical Experience 
Carboplatin-paclitaxel in combination with anti-PD-1 antibody agents has been studied in 
patients with advanced NSCLC in several studies. The combination has been well tolerated and 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 73 of 259 
 
has shown encouraging anti-tumor activity. Nivolumab 5 or 10 mg/kg and carboplatin-paclitaxel 
combination treatment was evaluated in the CheckMate 012 study, a Phase 1, multicohort study 
exploring the safety and efficacy of nivolumab monotherapy and nivolumab in combination with 
current standard therapies in first-line advanced NSCLC. The safety profile of combination 
treatment was found to be manageable, and the clinical activity of nivolumab 5 mg/kg and 
carboplatin-paclitaxel combination treatment showed evidence of efficacy.95 
Carboplatin-paclitaxel was administered in combination with the anti-PD-1 antibody 
pembrolizumab in the KEYNOTE-021 study in patients with advanced non-squamous NSCLC. 
The study concluded that pembrolizumab and carboplatin-paclitaxel combination treatment may 
be an effective and tolerable first-line treatment option for patients with advanced non-squamous 
NSCLC.96  
This study is the first to assess TSR-042 and carboplatin-paclitaxel combination treatment; 
therefore, no clinical data are currently available for TSR-042 and carboplatin-paclitaxel 
combination treatment. 
4.2.7. 
Carboplatin-Paclitaxel in Combination with Bevacizumab  
Carboplatin-paclitaxel and bevacizumab combination treatment was evaluated in patients with 
recurrent or advanced non–small-cell lung (Stage IIIB or IV) cancer (Eastern Cooperative 
Oncology Group (ECOG-4599)). These patients were assigned to treatment with carboplatin-
paclitaxel alone or carboplatin-paclitaxel plus bevacizumab. The median survival was 12.3 
months for patients assigned to carboplatin-paclitaxel plus bevacizumab treatment, whereas the 
median survival for patients assigned to carboplatin-paclitaxel alone was 10.3 months (HR, 0.79; 
P = 0.003). It was concluded that the addition of bevacizumab to carboplatin-paclitaxel had a 
significant survival benefit. However, patients showed an increased toxic effect, particularly 
febrile neutropenia and pulmonary hemorrhage.97 
The combination of chemotherapy and bevacizumab has also been evaluated in in patients with 
recurrent, persistent, or metastatic cervical cancer (GOG 240). The addition of bevacizumab to 
combination chemotherapy in these patients was associated with an improvement of 3.7 months 
in median overall survival. Bevacizumab, as compared with chemotherapy alone, was associated 
with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic 
events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 
0%).98 
4.2.8. 
Carboplatin-Pemetrexed in Combination With Anti-PD-1 Inhibitors  
The addition of the PD-l inhibitor pembrolizumab to carboplatin and pemetrexed has shown 
improved efficacy and a favorable benefit-risk profile in patients with chemotherapy-naive, 
advanced non-squamous NSCLC99. 
The comparison of the combination of pemetrexed and a platinum-based drug plus either 
pembrolizumab or placebo in patients with non-squamous NSCLC with any level of PD-L1 
expression has been studied in the KEYNOTE-189 study. Addition of pembrolizumab to 
standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer 
overall survival and PFS than chemotherapy alone. Median progression-free survival was 8.8 
months vs 4.9 months (HR = 0.52, P < .001). Progression-free survival at 12 months was 34.1% 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 74 of 259 
 
vs 17.3%. Overall survival at 12 months was 69.2% in the pembrolizumab group vs 49.4% in the 
placebo group (hazard ratio [HR] = 0.49, P < .001). Median overall survival was not reached in 
the pembrolizumab group vs 11.3 months in the placebo group (hazard ratio for disease 
progression or death, 0.52; 95% CI, 0.43 to 0.64; P<0.001).  
The addition of pembrolizumab to pemetrexed and chemotherapy showed a similar incidence of 
adverse events as chemotherapy regimens involving only pemetrexed and a platinum-based drug. 
The incidence of most immune-mediated adverse events was not higher with pembrolizumab 
combination therapy than that previously observed with pembrolizumab monotherapy. 
4.2.9. 
Carboplatin–Nab-Paclitaxel in Combination With Anti-PD-1 Inhibitors 
In the Keynote 407 study, pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel 
showed significant improvement in OS over chemotherapy alone in patients with metastatic 
squamous NSCLC. Pembrolizumab plus chemotherapy significantly improved OS (median, 
15.9 months vs 11.3 months; HR, 0.64; P = 0.0008) over chemotherapy alone. PFS (median, 
6.4 months vs 4.8 months; HR, 0.56; P < 0.0001) and ORR (57.9% vs 38.4%; P = 0.0004) were 
also improved with pembrolizumab plus chemotherapy, and responses were more durable. The 
safety profile was consistent with safety profiles of pembrolizumab and chemotherapy, and no 
new safety signals were identified.100 
The Impower 131 study met its primary endpoint of investigator-assessed PFS with atezolizumab 
plus carboplatin and nab-paclitaxel compared to nab-paclitaxel alone in patients with advanced 
squamous NSCLC (median PFS, 6.3 months vs 5.6 months; HR, 0.71). The combination had a 
manageable safety profile consistent with the known safety risks of the individual therapies, and 
no new safety signals were observed.101 
4.2.10. 
Combination of Niraparib and Bevacizumab 
The combination of a PARP inhibitor and an angiogenesis inhibitor has the potential for 
improved PFS benefits in patients with or without HRD.  
As described earlier, tumor cells with a deficiency in homologous recombination are exquisitely 
sensitive to PARP inhibitors due to synthetic lethality. It has been observed that, for tumors 
without genetic or epigenetic defects in homologous recombination pathway genes, a functional 
state of HRD may be induced by hypoxia through transcriptional downregulation of homologous 
recombination-related genes, including RAD51 and BRCA1. In addition, cyclic (acute) hypoxia 
and reoxygenation can induce both single-strand and double-strand DNA breaks within tumor 
cells due to increased levels of reactive oxygen species. These 2 mechanisms working together 
lead to heightened sensitivity to PARP inhibitors when cells are under hypoxic stress exerted by 
angiogenesis inhibitors. It has been observed that PARP inhibitors selectively induce apoptosis 
in hypoxic tumor regions in vivo, supporting the idea of contextual synthetic lethality between 
hypoxia-induced functional HRD and PARP inhibition. In the clinical setting, preliminary 
evidence of clinical efficacy has been observed in patients with platinum-sensitive ovarian 
cancer treated with either niraparib combined with bevacizumab (ENGOT-OV24/AVANOVA 
trial) or olaparib combined with cediranib (Phase II), irrespective of their BRCA mutation or 
HRD status. These data provide a strong rationale for combining a PARP inhibitor with an 
angiogenesis inhibitor. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 75 of 259 
 
To validate the hypothesis that tumors without HRD can be effectively treated with the 
combination of niraparib and bevacizumab, the HRD status for pretreatment tumor tissue will be 
determined using the Myriad myChoice® HRD test. 
The combination of niraparib and bevacizumab treatment is currently being explored in patients 
with recurrent platinum-sensitive ovarian cancer as part of an ongoing Phase 1/2 study 
(AVANOVA).102 Phase 1 of the study (dose escalation) has determined the recommended Phase 
2 dose in this population to be 300 mg niraparib orally once daily and 15 mg/kg bevacizumab via 
intravenous (IV) infusion every 3 weeks. Results to date, although limited, indicate clinical 
activity of the combination in this patient population. 
Overall, the combination of niraparib and bevacizumab appears to be safe for administration, 
with a manageable safety profile. AEs observed to date are consistent with those of the 
individual components and are readily managed through routine laboratory testing (i.e., CBC), 
clinical surveillance (i.e., blood pressure monitoring), and adherence to the recommended dose 
modifications. 
4.2.11. 
Combination of PD-L1 Inhibitor, PARP Inhibitor, and Anti-Angiogenic Agent 
There is no previous clinical experience of combination treatment that includes a PD-1 inhibitor. 
However, the efficacy and safety of the combination of a PD-L1 inhibitor, PARP inhibitor and 
an anti-angiogenic agent have been studied in a Phase 1/2 study in women’s cancers.103,104 Data 
from the study indicates anti-cancer activity of the triplet combination, especially in ovarian 
cancer. At the dosing levels explored, the combination was tolerable and hemotoxicity and 
cardiovascular toxicity observed in the study were consistent with PARPi-class and anti-VEGFR 
treatments, respectively.   
4.2.12. 
Combination of TSR-042 and TSR-022 
While a significant proportion of patients with NSCLC benefit from anti-PD-1 monotherapy, 
there are many patients who do not benefit from anti-PD-1 treatment. The lack of benefit in these 
patients may be due to additional immunosuppressive mechanisms such as those mediated by 
TIM-3. Early combination treatment enables the assessment of TIM-3 and PD-1 blockade to 
address de novo resistance to anti-PD-1 blockade while preventing one of the mechanisms that 
may result in resistance to anti-PD-1 monotherapy.  
There are several lines of evidence that suggest that the activity of anti-TIM-3 will be optimized 
in the setting of concurrent treatment with anti-PD-1. First, the blockade of TIM-3 may result in 
an increase in IFN and IFN-induced PD-L1 expression.27, 28 Second, the majority of TIM-3 
expressing cells also express PD-1.57-59 Third, treatment with anti-PD-1 has been shown to 
increase TIM-3 expression.24 Combination therapy of anti-TIM-3 and anti-PD-1 may therefore 
provide improved clinical activity compared to either monotherapy.  
The combination of TSR-042 and TSR-022 treatment is currently being evaluated in patients 
with advanced solid tumors as part of an ongoing Phase 1 study (Study 4020-01-001). In Part 1c 
of the study, patients receive TSR-042 (500 mg) in combination with TSR-022 (100, 300, or 
900 mg) via IV infusion every 3 weeks.  
As of 19 May 2018, 142 subjects were treated with TSR-022 in combination with TSR-042. The 
majority (85.2%) of the 142 subjects who received TSR-022 in combination with TSR-042 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 76 of 259 
 
experienced TEAEs; 42.3% experienced TEAEs considered by the Investigator to be related to 
study drug. TEAEs of Grade ≥3 were reported in 35.9% of subjects, and 6.3% experienced 
Grade ≥3 TEAEs considered by the Investigator to be related to study drug. SAEs were reported 
in 27.5% of subjects; 6.3% experienced SAEs considered by the Investigator to be related to 
study drug. Seven subjects (4.9%) discontinued study drug due to a TEAE; 1 subject (0.7%) 
experienced a TEAE leading to study drug discontinuation that was considered by the 
Investigator to be related to study drug. Two subjects (1.4%) had TEAEs leading to death; 
neither were assessed as related to study drug by the Investigator. 
Please refer to the current TSR-022 IB for further information.  
4.3. 
Rationale for the Current Study 
It is possible that increased DNA damage from treatment with a PARP inhibitor or chemotherapy 
agents (e.g., carboplatin-paclitaxel or carboplatin-pemetrexed) combined with reduced 
angiogenesis due to treatment with a VGFR inhibitor may lead to an increase in the neoantigen 
expression and a more robust antigenic environment. In this stimulated immune environment, 
treatment with an anti-PD-1 inhibitor may result in improved clinical efficacy. 
Synergistic interactions have been observed between immune checkpoint inhibitors and PARP 
inhibitors; nonclinical studies in syngeneic mouse models have shown an increased response rate 
to combination of anti-PD-1 and niraparib over either agent alone, further supporting the 
investigation of this combination in patients (see Section 4.2.5.1). The combination was well 
tolerated in all of these nonclinical studies including models of BRCA1-deficient ovarian cancer, 
BRCA1-null ovarian cancer, ovarian carcinoma, and lung squamous cell cancer.84-88 PARP 
inhibitor can increase the number of CD8+ T cells and natural killer cells, as well as their 
production of interferon-gamma and tumor necrosis factor alpha, resulting in an improved 
response to checkpoint blockade.85  
Combination treatment with an anti-PD-1 antibody agent and PARP inhibitor was evaluated in a 
dose escalation Phase 1b study and was shown to be tolerable with early signs of efficacy in 
patients with advanced solid tumors, including ovarian and breast cancers.105 Given the unmet 
medical need of patients with advanced or metastatic cancer, their non-overlapping safety and 
metabolic profiles (see the niraparib IB and the TSR-042 IB for details), and nonclinical and 
clinical data suggesting possible synergistic interaction between immune checkpoint inhibitors 
and PARP inhibitors along with a potential overlap in PD-l- and PARP-sensitive patient 
populations, the present clinical study is designed to evaluate TSR-042 and niraparib 
combination treatment in this patient population.  
Accumulating nonclinical data suggest that chemotherapy agents such as carboplatin and 
paclitaxel may activate immune responses targeting tumor cells, in addition to their direct 
cytotoxic effects (see Section 4.2.6.1).69 In nonclinical models, platinum-based agents have been 
suggested to increase direct cytostatic-mediated activation of T cells by several mechanisms, 
including down-regulation of PD-L2 and increased ATP and high mobility group protein box-1 
release from dying cells, whereas for paclitaxel, several immunostimulatory effects on the 
immune system have been reported.90-94 These data suggest that chemotherapy agents may 
modulate the tumor microenvironment, suggesting a potential synergistic interaction between 
chemotherapy and immune checkpoint inhibitors, such as those targeting PD-1 or PD-L1. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 77 of 259 
 
Carboplatin-paclitaxel in combination with anti-PD-1 antibody agents has been evaluated in 
patients with advanced NSCLC in several studies (see Section 4.2.6.2). The combination of 
carboplatin-paclitaxel with nivolumab was well tolerated with encouraging anti-tumor activity as 
a first-line therapy in patients with advanced NSCLC.95 In patients with advanced non-squamous 
NSCLC, combination treatment with carboplatin-paclitaxel and pembrolizumab was shown to be 
an effective and tolerable first-line treatment option.96 These data suggest a potential synergistic 
anti-cancer effect of carboplatin-paclitaxel and an anti-PD-1 inhibitor, such as TSR-042.  
The addition of the PD-l inhibitor pembrolizumab to carboplatin and pemetrexed has shown 
improved efficacy and a favorable benefit-risk profile in patients with chemotherapy-naive, 
advanced non-squamous NSCLC.99 
Pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel showed significant 
improvement in OS over chemotherapy alone in patients with metastatic squamous NSCLC. PFS 
and ORR were also improved with pembrolizumab plus chemotherapy, and responses were more 
long-lasting.101 
As mentioned above, the strategy of combining a PARP inhibitor, VEGF inhibitor, and an 
immune checkpoint inhibitor was tested in a Phase 1/2 study and showed acceptable safety data 
and encouraging anti-cancer effects, suggesting potential synergistic effect of the combination.103  
In the IMPOWER-150 study, carboplatin-paclitaxel-bevacizumab in combination with the anti-
PD-L1 antibody, atezolizumab, was studied in previously untreated advanced non-squamous cell 
lung cancer patients.106 Results showed significant improvement in OS and PFS: the median OS 
with atezolizumab/ bevacizumab/chemotherapy was 19.8 months compared with 14.9 months for 
bevacizumab/chemotherapy (HR 0.76; 95% CI 0.63, 0.93) and the median PFS was 8.3 versus 
6.8 months (hazard ratio [HR] 0.62; 95% CI 0.52, 0.74). The overall safety profile of the 
combination was acceptable.  
The combination of TSR-042 (500 mg) and TSR-022 (900 mg) treatment is currently being 
evaluated in patients with advanced solid tumors as part of an ongoing Phase 1 study 
(Study 4020-01-001). Results to date, although limited, indicate that TSR-042/TSR-022 
combination therapy is safe and has a manageable safety profile. 
This study is the first to assess TSR-042 and niraparib combination treatment; TSR-042 and 
carboplatin-paclitaxel combination treatment; TSR-042, niraparib, and bevacizumab 
combination treatment;TSR-042, carboplatin-paclitaxel, and bevacizumab combination 
treatment; TSR-042 and carboplatin-pemetrexed combination treatment; TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment; TSR-042 and carboplatin–nab-paclitaxel 
combination treatment; TSR-042, TSR-022, and carboplatin–nab-paclitaxel combination 
treatment; and TSR-042, TSR-022, and carboplatin-paclitaxel combination treatment; therefore, 
the PK profiles of niraparib, TSR-042, and TSR-022 will be evaluated. Anti-drug antibodies 
(ADAs) for TSR-042 and TSR-022 (as applicable) during all combination treatments will be 
evaluated as well. The study will be conducted in conformance with the protocol, Good Clinical 
Practice (GCP), and applicable regulatory requirements. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 78 of 259 
 
5. 
STUDY OBJECTIVES AND PURPOSE 
5.1. 
Primary Objectives 
The primary objectives for Part A of this study are as follows: 
 To evaluate DLTs of TSR-042 and niraparib combination treatment during the first 
cycle of treatment in patients with advanced or metastatic cancer and to establish a 
RP2D. 
 To evaluate the safety and tolerability of TSR-042 and niraparib combination 
treatment 
The primary objectives for Part B of this study are as follows: 
 To evaluate DLTs of TSR-042 and carboplatin-paclitaxel combination treatment 
during the first cycle of treatment in patients with advanced or metastatic cancer and 
to confirm an RP2D 
 To evaluate the safety and tolerability of TSR-042 and carboplatin-paclitaxel 
combination treatment 
The primary objectives for Part C of this study are as follows: 
 To evaluate DLTs of TSR-042, niraparib, and bevacizumab combination treatment 
during the first cycle of treatment in patients with advanced or metastatic cancer and 
to establish an RP2D 
 To evaluate the safety and tolerability of TSR-042, niraparib, and bevacizumab 
combination treatment 
The primary objectives for Part D of this study are as follows: 
 To evaluate DLTs of TSR-042, carboplatin-paclitaxel, and bevacizumab combination 
treatment during the first cycle of treatment in patients in whom 
carboplatin-paclitaxel and bevacizumab combination treatment is considered a 
reasonable therapy, and to confirm an RP2D 
 To evaluate the safety and tolerability of TSR-042, carboplatin-paclitaxel, and 
bevacizumab combination treatment 
The primary objectives for Part E of this study are as follows: 
 To evaluate DLTs of TSR-042 and carboplatin-pemetrexed combination treatment 
during the first cycle of treatment, as first-line treatment in patients with advanced or 
metastatic non-squamous NSCLC, and to confirm an RP2D 
 To evaluate the safety and tolerability of TSR-042 and carboplatin-pemetrexed 
combination treatment 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 79 of 259 
 
The primary objectives for Part F of this study are as follows: 
 To evaluate DLTs of TSR-042, TSR-022, and carboplatin-pemetrexed combination 
treatment during the first cycle of treatment, as first-line treatment in patients with 
advanced or metastatic non-squamous NSCLC, and to confirm an RP2D 
 To evaluate the safety and tolerability of TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment 
The primary objectives for Part G of this study are as follows: 
 To evaluate DLTs of TSR-042 and carboplatin–nab-paclitaxel combination treatment 
during the first cycle of treatment, as first-line treatment in patients with advanced or 
metastatic NSCLC, and to confirm an RP2D 
 To evaluate the safety and tolerability of TSR-042 and carboplatin–nab-paclitaxel 
combination treatment 
The primary objectives for Part H of this study are as follows: 
 To evaluate DLTs of TSR-042, TSR-022, and carboplatin–nab-paclitaxel 
combination treatment during the first cycle of treatment, as first-line treatment in 
patients with advanced or metastatic NSCLC, and to confirm an RP2D 
 To evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin–
nab-paclitaxel combination treatment 
The primary objectives for Part I of this study are as follows: 
 To evaluate DLTs of TSR-042, TSR-022, and carboplatin-paclitaxel combination 
treatment during the first cycle of treatment, as first-line treatment in patients with 
advanced or metastatic NSCLC, and to confirm an RP2D 
 To evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin-
paclitaxel combination treatment 
5.2. 
Secondary Objectives 
The secondary objectives for Part A of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
objective response rate (ORR), duration of response (DOR), disease control rate 
(DCR), and PFS by Response Evaluation Criteria in Solid Tumors version 1.1 
(RECIST v1.1) 
 To evaluate the PK of niraparib, its major metabolite M1, and TSR-042 during 
TSR-042 and niraparib combination treatment 
 To evaluate ADAs of TSR-042 during TSR-042 and niraparib combination treatment  
The secondary objectives for Part B of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 80 of 259 
 
 To evaluate the PK of TSR-042 during TSR-042 and carboplatin-paclitaxel 
combination treatment 
 To evaluate ADAs of TSR-042 during TSR-042 and carboplatin-paclitaxel 
combination treatment 
The secondary objectives for Part C of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 
 To evaluate the PK of niraparib, its major metabolite M1, and TSR-042 during 
TSR-042, niraparib and bevacizumab combination treatment 
 To evaluate ADAs of TSR-042 during TSR-042, niraparib and bevacizumab 
combination treatment  
The secondary objectives for Part D of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 
 To evaluate the PK of TSR-042 during TSR-042, carboplatin-paclitaxel and 
bevacizumab combination treatment 
 To evaluate ADAs of TSR-042 during TSR-042, carboplatin-paclitaxel and 
bevacizumab combination treatment 
The secondary objectives for Part E of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 
 To evaluate the PK of TSR-042 during TSR-042 and carboplatin-pemetrexed 
combination treatment 
 To evaluate ADAs of TSR-042 during TSR-042 and carboplatin-pemetrexed 
combination treatment 
The secondary objectives for Part F of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 
 To evaluate the PK of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment 
 To evaluate ADAs of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment 
The secondary objectives for Part G of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 81 of 259 
 
 To evaluate the PK of TSR-042 during TSR-042 and carboplatin–nab-paclitaxel 
combination treatment 
 To evaluate ADAs of TSR-042 during TSR-042 and carboplatin–nab-paclitaxel 
combination treatment 
The secondary objectives for Part H of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 
 To evaluate the PK of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin–nab-paclitaxel combination treatment 
 To evaluate ADAs of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin–nab-paclitaxel combination treatment 
The secondary objectives for Part I of the study are as follows: 
 To evaluate measures of clinical benefit as assessed by the Investigators, including 
ORR, DOR, DCR, and PFS by RECIST v1.1 
 To evaluate the PK of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin-paclitaxel combination treatment 
 To evaluate ADAs of TSR-042 and TSR-022 during TSR-042, TSR-022, and 
carboplatin-paclitaxel combination treatment 
5.3. 
Exploratory Objectives 
The exploratory objectives for Part A of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042 and niraparib 
combination treatment based on the pretreatment biomarker profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042 and niraparib combination treatment and correlate with 
clinical benefit 
The exploratory objectives for Part B of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042 and 
carboplatin-paclitaxel combination treatment based on the pretreatment biomarker 
profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042 and carboplatin-paclitaxel combination treatment and 
correlate with clinical benefit 
The exploratory objectives for Part C of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042, niraparib and 
bevacizumab combination treatment based on the pretreatment biomarker profile 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 82 of 259 
 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042, niraparib and bevacizumab combination treatment and 
correlate with clinical benefit 
The exploratory objectives for Part D of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042, 
carboplatin-paclitaxel and bevacizumab combination treatment based on the 
pretreatment biomarker profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042, carboplatin-paclitaxel and bevacizumab combination 
treatment and correlate with clinical benefit 
The exploratory objectives for Part E of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042 and 
carboplatin-pemetrexed combination treatment based on the pretreatment biomarker 
profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042 and carboplatin-pemetrexed combination treatment and 
correlate with clinical benefit 
The exploratory objectives for Part F of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042, TSR-022, 
and carboplatin-pemetrexed combination treatment based on the pretreatment 
biomarker profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042, TSR-022, and carboplatin-pemetrexed treatment and 
correlate with clinical benefit 
The exploratory objectives for Part G of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042 and 
carboplatin–nab-paclitaxel combination treatment based on the pretreatment 
biomarker profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042 and carboplatin–nab-paclitaxel combination treatment and 
correlate with clinical benefit 
The exploratory objectives for Part H of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042, TSR-022, 
and carboplatin–nab-paclitaxel combination treatment based on the pretreatment 
biomarker profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042, TSR-022, and carboplatin–nab-paclitaxel treatment and 
correlate with clinical benefit 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 83 of 259 
 
The exploratory objectives for Part I of the study are as follows: 
 To explore biomarkers that may be predictive of benefit from TSR-042, TSR-022, 
and carboplatin-paclitaxel combination treatment based on the pretreatment 
biomarker profile 
 To explore changes in biomarkers (e.g., immune cells and immune proteins) in the 
blood following TSR-042, TSR-022, and carboplatin-paclitaxel treatment and 
correlate with clinical benefit 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 84 of 259 
 
6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design and Plan 
This is a multicenter, open-label, 9-part Phase 1b study evaluating the safety and preliminary 
efficacy of niraparib or niraparib/bevacizumab in combination with TSR-042 treatment and 
confirming the safety and tolerability of carboplatin-paclitaxel, carboplatin-paclitaxel/ 
bevacizumab, carboplatin-pemetrexed, carboplatin-pemetrexed/TSR-022, carboplatin–
nab-paclitaxel, TSR-022/carboplatin–nab-paclitaxel, and TSR-022/carboplatin-paclitaxel in 
combination with TSR-042 treatment in patients with advanced or metastatic cancer. 
Specifically, patients eligible for this study are as follows: 
 Part A (dose finding—TSR-042 and niraparib combination treatment): All comers, 
defined as patients with previously treated advanced or metastatic cancer  
 Part B (safety and tolerability evaluation—TSR-042 and carboplatin-paclitaxel 
combination treatment): Patients with advanced or metastatic cancer for which 
treatment with carboplatin and paclitaxel is indicated (e.g., including, but not limited 
to, NSCLC, ovarian cancer, and cervical cancer) 
 Part C (dose finding—TSR-042, niraparib and bevacizumab combination treatment): 
All comers, defined as patients with previously treated advanced or metastatic cancer  
 Part D (safety and tolerability evaluation—TSR-042, carboplatin-paclitaxel and 
bevacizumab combination treatment): in patients where carboplatin-paclitaxel and 
bevacizumab is considered a reasonable therapy 
 Part E (safety and tolerability evaluation—TSR-042 and carboplatin-pemetrexed 
combination treatment): as first-line treatment in patients with advanced or metastatic 
non-squamous NSCLC 
 Part F (safety and tolerability evaluation—TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment): as first-line treatment in patients 
with advanced or metastatic non-squamous NSCLC 
 Part G (safety and tolerability evaluation—TSR-042 and carboplatin–nab-paclitaxel 
combination treatment): as first-line treatment in patients with advanced or metastatic 
NSCLC 
 Part H (safety and tolerability evaluation—TSR-042, TSR-022, and carboplatin–
nab-paclitaxel combination treatment): as first-line treatment in patients with 
advanced or metastatic NSCLC 
 Part I (safety and tolerability evaluation—TSR-042, TSR-022, and carboplatin-
paclitaxel combination treatment): as first-line treatment in patients with advanced or 
metastatic NSCLC 
The study will include 9 parts: Parts A, B, C, D, E, F, G, H, and I. Part A will be a dose-finding 
evaluation conducted in all comers (12 to 24 patients) to determine the RP2D of niraparib in 
combination with TSR-042. Part B will evaluate the safety and tolerability of TSR-042 and 
carboplatin-paclitaxel combination treatment in approximately 12 patients with advanced or 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 85 of 259 
 
metastatic cancer for which carboplatin-paclitaxel is indicated.  Part C will be a dose-finding 
evaluation conducted in all comers (6 to 24 patients) to determine the RP2D of niraparib and 
bevacizumab in combination with TSR-042. Part D will evaluate the safety and tolerability of 
TSR-042, carboplatin-paclitaxel and bevacizumab combination treatment in 6 to 12 patients, in 
patients in whom carboplatin-paclitaxel and bevacizumab combination treatment is considered a 
reasonable therapy. Part E will evaluate the safety and tolerability of TSR-042 and 
carboplatin-pemetrexed combination treatment as first-line treatment in 6 to 12 patients with 
advanced or metastatic non-squamous NSCLC. Part F will evaluate the safety and tolerability of 
TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment as first-line treatment in 
6 to 24 patients with advanced or metastatic non-squamous NSCLC. Part G will evaluate the 
safety and tolerability of TSR-042 and carboplatin–nab-paclitaxel combination treatment as 
first-line treatment in 6 to 12 patients with advanced or metastatic NSCLC. Part H will evaluate 
the safety and tolerability of TSR-042, TSR-022, and carboplatin–nab-paclitaxel combination 
treatment as first-line treatment in 6 to 24 patients with advanced or metastatic NSCLC. Part I 
will evaluate the safety and tolerability of TSR-042, TSR-022, and carboplatin-paclitaxel 
combination treatment as first-line treatment in 6 to 24 patients with advanced or metastatic 
NSCLC. 
Enrollment of patients into Parts A, B, D, E, G, and I will occur concurrently. Part C will be 
initiated after dose level 1 (niraparib 200 mg) in Part A is determined to be safe. Part F will be 
initiated after TSR-042 and carboplatin-pemetrexed combination treatment in Part E is 
determined to be safe. Part H will be initiated after TSR-042 and carboplatin–nab-paclitaxel 
combination treatment in Part G is determined to be safe. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 86 of 259 
 
6.1.1. 
Overview 
The study design is provided in Figure 1. 
Figure 1: 
Study Design  
 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 87 of 259 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = adverse event; AUC = area under the plasma or serum concentration-time curve; D1 = Day 1; 
D21 = Day 21; DLT = dose-limiting toxicity; PK = pharmacokinetics; Q1W = every week; Q3W = every 3 weeks; 
Q6W = every 6 weeks; RP2D = recommended Phase 2 dose. 
a In addition to receiving niraparib (Part A), carboplatin-paclitaxel (Part B), niraparib and bevacizumab (Part C), 
carboplatin-paclitaxel and bevacizumab (Part D), carboplatin-pemetrexed (Part E), carboplatin-pemetrexed and 
TSR-022 (Part F), carboplatin–nab-paclitaxel (Part G), TSR-022 and carboplatin–nab-paclitaxel (Part H), and 
TSR-022 and carboplatin-paclitaxel (Part I) at the specified regimen, all patients will be administered TSR-042 at 
500 mg on Day 1 of every cycle (Q3W) for 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 will be 
administered to patients in Parts A, B, C, and D at 1,000 mg on Day 1 of every other cycle (Q6W) until the patient 
discontinues study treatment. Patients in Parts E, F, G, H, and I will continue to receive 500 mg on Day 1 of every 
cycle (Q3W) throughout the study. 
b The RP2D for TSR-042 and niraparib combination treatment (Part A); TSR-042 and carboplatin-paclitaxel 
combination treatment (Part B); TSR-042, niraparib, and bevacizumab combination treatment (Part C); TSR-042, 
carboplatin-paclitaxel, and bevacizumab combination treatment (Part D); TSR-042 and carboplatin-pemetrexed 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 88 of 259 
 
(Part E); TSR-042, carboplatin-pemetrexed, and TSR-022 (Part F); TSR-042 and carboplatin–nab-paclitaxel 
(Part G); TSR-042, TSR-022, and carboplatin–nab-paclitaxel (Part H); and TSR-042, TSR-022, and carboplatin-
paclitaxel (Part I) will be determined or confirmed based on an evaluation of multiple endpoints, which may 
include the DLT rate in first and subsequent cycles of combination treatment, the rate of dose modifications for 
non-DLT AEs, the ability to manage toxicities, PK, niraparib dose intensity, and signs of clinical efficacy. 
c 12 to 24 patients will be enrolled in Part A to determine the RP2D for TSR-042 and niraparib combination 
treatment.  
d Initially, dose level 1 in Part C will enroll 6 to 12 patients to determine the RP2D for TSR-042, niraparib, and 
bevacizumab combination treatment. Dose level 2 is optional. 
e  900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 (300 mg) if needed. Based on 
available safety information, the Sponsor may decide to test additional dose levels. 
6.1.2. 
General Study Conduct 
6.1.2.1. 
Part A: Dose Finding for TSR-042 and Niraparib Combination Treatment 
Determination of the RP2D for TSR-042 and niraparib combination treatment will be conducted 
using the dose levels described in Table 2. 
Table 2: 
Dose Regimen for TSR-042 and Niraparib Combination Treatment 
Dose Level 
Niraparib Dose 
TSR-042 Dose 
1 
200 mg administered on Days 1 to 21 repeated Q3W 
500 mg on Day 1 of every cycle 
(Q3W) for 4 cycles, followed by 
1,000 mg on Day 1 of every other 
cycle (Q6W) beginning on 
Day 1/Cycle 5  
2 
300 mg administered on Days 1 to 21 repeated Q3W 
Abbreviations: Q3W = every 3 weeks; Q6W = every 6 weeks. 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 
who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤1 patient 
experiences a DLT (see DLT definition in Section 6.1.2.3), dose level 1 will be considered safe. 
If 2 of 6 patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If 12 
patients are enrolled at dose level 1 and ≤3 of 12 patients experience DLTs, dose level 1 will be 
considered safe. The combination therapy will be considered unsafe if ≥3 of 6 or ≥4 of 
12 patients experience DLTs during Cycle 1 (see Part A dose-finding scheme below). However, 
when determining the RP2D, the Sponsor will review and consider safety data from all patients 
treated with the combination therapy. Note: Part A has been completed as of Amendment 2. 
Once dose level 1 (200 mg) is determined to be safe, the decision to open the next higher dose 
level (dose level 2) will be made based on evaluation of safety data from dose level 1. Dose 
level 2 (300 mg) will be opened only if less than one-third of evaluable patients (i.e., ≤1 of 
6 patients or ≤3 of 12 patients) at dose level 1 experience a DLT during Cycle 1. Patients at dose 
level 2 will be enrolled using the same 6 + 6 scheme used at dose level 1. For patients in Part A, 
the dose of niraparib may be increased after Cycle 2 to a higher dose level that has been found to 
be safe during the dose-escalation phase following discussion with the Sponsor. No further dose 
escalation will be evaluated if dose level 2 is reached. 
The Part A dose-finding scheme is summarized in Figure 2. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 89 of 259 
 
Figure 2: 
Part A Dose-Finding Scheme for TSR-042 and Niraparib Combination 
Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Niraparib will be administered at the specified dose level as described in Table 2. In addition to receiving niraparib 
at the specified regimen, all patients will be administered TSR-042 at 500 mg on Day 1 of every cycle (Q3W) for 
4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 will be administered at 1,000 mg on Day 1 of every other cycle 
(Q6W). 
Recommended Phase 2 Dose for TSR-042 and Niraparib Combination Treatment 
The RP2D for TSR-042 and niraparib combination treatment will be a dose with DLTs observed 
in less than one-third of evaluable patients (i.e., ≤1 of 6 patients or ≤3 of 12 patients) during 
Cycle 1 of combination treatment and will be determined following discussion and agreement 
between the Investigators and Sponsor based on evaluation of multiple endpoints, which may 
include the DLT rate in first and subsequent cycles of combination treatment, the rate of dose 
modifications for non-DLT AEs, the ability to manage toxicities, PK, niraparib dose intensity, 
and signs of clinical efficacy. The goal will be to identify the dose and regimen of niraparib with 
the greatest dose intensity that can be safely combined with the recommended dose and regimen 
of TSR-042. 
Duration of Study Treatment 
Patients enrolled in Part A may continue TSR-042 and niraparib combination treatment for up to 
2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 90 of 259 
 
decision, or death. Patients who have not progressed at 2 years will be given the option to 
continue on TSR-042 and niraparib combination treatment beyond 2 years if they are tolerating 
and benefiting from treatment and after consultation with the Sponsor. Patients with confirmed 
PD may continue study treatment at the Investigator’s discretion until the Investigator has 
determined that the patient is no longer experiencing clinical benefit or until study treatment is 
no longer tolerated by the patient.   
6.1.2.2. 
Part B: Safety and Tolerability Evaluation for TSR-042 and 
Carboplatin-Paclitaxel Combination Treatment 
Confirmation of the RP2D for TSR-042 and carboplatin-paclitaxel combination treatment will be 
conducted using the dose level described in Table 3. 
Table 3: 
Dose Regimen for TSR-042 and Carboplatin-Paclitaxel Combination 
Treatment 
Dose Level 
Carboplatin-Paclitaxel Dose 
TSR-042 Dose 
1 
Carboplatina AUC of 5 or 6 on Day 1 Q3W and 
paclitaxel 175 mg/m2 on Day 1 Q3W administered 
for 4 to 6 cycles as clinically indicated 
500 mg on Day 1 of every cycle Q3W for 4 
cycles, followed by 1,000 mg on Day 1 of 
every other cycle (Q6W) beginning on Day 
1/Cycle 5  
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks; 
Q6W = every 6 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer 
therapies and pre-existing medical conditions. 
A cohort of approximately 12 patients will be enrolled at dose level 1 in Part B. After all patients 
who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤3 patients 
experience a DLT (see DLT definition in Section 6.1.2.3), TSR-042 and carboplatin-paclitaxel 
combination treatment will be considered safe. The combination therapy will be considered 
unsafe if ≥4 of 12 patients experience DLTs during Cycle 1 (see Part B dose confirmation 
scheme below). However, when determining the RP2D, the Sponsor will review and consider 
safety data from all patients treated with the combination therapy. Note: Part B has been 
completed as of Amendment 2. 
The Part B dose confirmation scheme is summarized in Figure 3. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 91 of 259 
 
Figure 3: 
Part B Dose Confirmation Scheme for TSR-042 and Carboplatin-Paclitaxel 
Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Carboplatin-paclitaxel will be administered at the specified dose level as described in Table 3. In addition to 
receiving carboplatin-paclitaxel at the specified regimen, patients will be administered TSR-042 at 500 mg on 
Day of every cycle (Q3W) for 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 will be administered at 
1,000 mg on Day 1 of every other cycle (Q6W). 
Recommended Phase 2 Dose for Carboplatin-Paclitaxel and TSR-042 
The RP2D for TSR-042 and carboplatin-paclitaxel combination treatment will be confirmed 
following discussion and agreement between the Investigators and Sponsor based on evaluation 
of multiple endpoints, which may include the DLT rate in first and subsequent cycles of 
combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
Duration of Study Treatment 
Patients enrolled in Part B may continue TSR-042 and carboplatin-paclitaxel combination 
treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 
monotherapy for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. Continued treatment with TSR-042 beyond 2 years 
may be considered following discussion between the Sponsor and Investigator. 
6.1.2.3. 
Part C: Dose Finding for TSR-042, Niraparib, and Bevacizumab Combination 
Treatment  
Determination of the RP2D for TSR-042, niraparib, and bevacizumab combination treatment 
will be conducted using the dose levels described in Table 4. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 92 of 259 
 
Table 4: 
Dose Regimen for TSR-042, Niraparib and Bevacizumab Combination 
Treatment 
Dose Level 
Niraparib Dose 
TSR-042 Dose 
Bevacizumab Dose 
1 
200 mg administered on 
Days 1 to 21 repeated 
Q3W 
500 mg on Day 1 of every 
cycle (Q3W) for 4 cycles, 
followed by 1,000 mg on 
Day 1 of every other 
cycle (Q6W) beginning 
on Day 1/Cycle 5  
 
15 mg/kg on Day 1 of 
every 21-day cycle Q3W 
for up to 15 months 
2 (optional) 
300 mg administered on 
Days 1 to 21 repeated 
Q3W 
Abbreviations: Q3W = every 3 weeks; Q6W = every 6 weeks. 
At dose level 1 (200 mg), a cohort of 6 patients will be enrolled initially. After all patients in 
dose level 1 who are evaluable for safety have completed Cycle 1 of combination treatment, if 
≤1 patient experiences a DLT (see DLT Assessment below), dose level 1 will be considered safe. 
If 2 of 6 patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If 12 
patients are enrolled at dose level 1 and ≤3 of 12 patients experience DLTs, dose level 1 will be 
considered safe. The combination therapy will be considered unsafe if ≥3 of 6 or ≥4 of 12 
patients experience DLTs during Cycle 1 (see Part C dose-finding scheme below). However, 
when determining the RP2D, the Sponsor will review and consider safety data from all patients 
treated with the combination therapy. 
For patients in Part C, the dose of niraparib may be increased after Cycle 2 to a higher dose level 
that has been found to be safe during the dose-escalation phase following discussion with the 
Sponsor. No further dose escalation will be evaluated if dose level 2 is reached.   
The decision to open dose level 2 (300 mg) will be made by the Sponsor based on evaluation of 
safety data from dose level 1. Dose level 2 will be optional and opened only if less than one-third 
of evaluable patients (i.e., ≤1 of 6 patients or ≤3 of 12 patients) at dose level 1 experience a DLT 
during Cycle 1. 
The Part C dose-finding scheme is summarized in Figure 4.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 93 of 259 
 
Figure 4: 
Part C Dose-Finding Scheme for TSR-042, Niraparib, and Bevacizumab 
Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Niraparib and bevacizumab will be administered at the specified dose level as described in Table 4 (Dose Regimen 
for TSR-042, Niraparib and Bevacizumab Combination Treatment). In addition to receiving niraparib at the 
specified regimen, all patients will be administered TSR-042 at 500 mg on Day 1 of every cycle (Q3W) for 
4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 will be administered at 1,000 mg on Day 1 of every other cycle 
(Q6W). Bevacizumab 15 mg/kg will be administered on Day 1 of every 21-day cycle Q3W for up to 15 months. 
Recommended Phase 2 Dose for TSR-042, Niraparib, and Bevacizumab Combination 
Treatment 
The RP2D for TSR-042, niraparib, and bevacizumab combination treatment will be a dose with 
DLTs observed in less than one-third of evaluable patients (i.e., ≤1 of 6 patients or ≤3 of 12 
patients) during Cycle 1 of combination treatment and will be determined following discussion 
and agreement between the Investigators and Sponsor based on evaluation of multiple endpoints, 
which may include the DLT rate in first and subsequent cycles of combination treatment, the rate 
of dose modifications for non-DLT AEs, the ability to manage toxicities, PK, niraparib dose 
intensity, and signs of clinical efficacy. The goal will be to identify the dose and regimen of 
niraparib with the greatest dose intensity that can be safely combined with the recommended 
dose and regimens of TSR-042 and bevacizumab. 
Duration of Study Treatment 
Patients enrolled in Part C may continue TSR-042, niraparib, bevacizumab combination 
treatment for up to 15 months followed by TSR-042 and niraparib combination treatment for the 
remainder of 2 years or until disease progression, unacceptable toxicity, patient withdrawal, 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 94 of 259 
 
Investigator’s decision, or death. Patients who have not progressed at 2 years will be given the 
option to continue on TSR-042 and niraparib combination treatment beyond 2 years if they are 
tolerating and benefiting from treatment and after consultation with the Sponsor. Patients with 
confirmed PD may continue study treatment at the Investigator’s discretion until the Investigator 
has determined that the patient is no longer experiencing clinical benefit or until study treatment 
is no longer tolerated by the patient.  
6.1.2.4. 
Part D: Safety and Tolerability Evaluation for TSR-042, Carboplatin-Paclitaxel 
and Bevacizumab Combination Treatment 
Confirmation of the RP2D for TSR-042, carboplatin-paclitaxel and bevacizumab combination 
treatment will be conducted using the dose level described in the table below: 
Table 5: 
Dose Regimen for TSR-042 and Carboplatin-Paclitaxel Combination 
Treatment 
Dose Level 
Carboplatin-Paclitaxel 
Dose 
TSR-042 Dose 
Bevacizumab Dose 
1 
Carboplatina AUC of 5 or 
6 on Day 1 Q3W and 
paclitaxel 175 mg/m2 on 
Day 1 Q3W administered 
for 4 to 6 cycles as 
clinically indicated 
500 mg on Day 1 of every 
cycle (Q3W) for 4 cycles, 
followed by 1,000 mg on 
Day 1 of every other 
cycle (Q6W) beginning 
on Day 1/Cycle 5  
15 mg/kg on Day 1 of 
every 21-day cycle Q3W 
for up to 15 months 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks; 
Q6W = every 6 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer 
therapies and pre-existing medical conditions. 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 
who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤1 patient 
experiences a DLT (see DLT Assessment below), dose level 1 will be considered safe. If 
2 patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If 
≤3 of 12 patients experience DLTs at dose level 1, the combination will be considered safe. The 
combination therapy will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs 
during Cycle 1 (see Part D dose confirmation scheme below). However, when determining the 
RP2D, the Sponsor will review and consider safety data from all patients treated with the 
combination therapy. Note: Part D has been completed as of Amendment 2. 
The RP2D for TSR-042, carboplatin-paclitaxel and bevacizumab combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles 
of combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
The Part D dose confirmation scheme is summarized in Figure 5. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 95 of 259 
 
Figure 5: 
Part D Dose Confirmation Scheme for TSR-042, Carboplatin-Paclitaxel and 
Bevacizumab Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a Carboplatin-paclitaxel and bevacizumab will be administered at the specified dose level as described in Table 5 
(Dose Regimen for TSR-042, Carboplatin-Paclitaxel and Bevacizumab Combination Treatment). In addition to 
receiving carboplatin-paclitaxel and bevacizumab the specified regimen, patients will be administered TSR-042 at 
500 mg on Day 1 of every cycle (Q3W) for 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 will be 
administered at 1,000 mg on Day 1 of every other cycle (Q6W). Bevacizumab 15 mg/kg will be administered on 
Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
Recommended Phase 2 Dose for Carboplatin-Paclitaxel, TSR-042, and Bevacizumab 
The RP2D for TSR-042, carboplatin-paclitaxel, and bevacizumab combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles 
of combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
Duration of Study Treatment 
Patients enrolled in Part D may continue TSR-042, carboplatin-paclitaxel, and bevacizumab 
combination treatment for 4 to 6 cycles, as indicated, after which, patients may continue 
bevacizumab for up to 15 months and TSR-042 for up to 2 years or until disease progression, 
unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Continued treatment 
with TSR-042 beyond 2 years may be considered following discussion between the Sponsor and 
Investigator.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 96 of 259 
 
6.1.2.5. 
Part E: Safety and Tolerability for TSR-042 and Carboplatin-Pemetrexed 
Combination Treatment 
Confirmation of the RP2D for TSR-042, pemetrexed, and carboplatin combination treatment will 
be conducted using the dose levels described in Table 6. 
Table 6: 
Dose Regimen for TSR-042 and Carboplatin-Pemetrexed Combination 
Treatment 
Dose Level 
TSR-042 Dose 
Pemetrexed Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of every 
cycle Q3W 
500 mg/m2 Day 1 Q3W 
(with vitamin 
supplementation) 
AUC of 5 or 6 on Day 1 
Q3W administered for 4 
to 6 cycles as clinically 
indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer 
therapies and pre-existing medical conditions. 
 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 
who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient 
experiences a DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 
patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 
patients experience DLTs, the combination will be considered safe. The combination therapy 
will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see 
Part E dose confirmation scheme below). However, when determining the RP2D, the Sponsor 
will review and consider safety data from all patients treated with the combination therapy. 
The Part E dose confirmation scheme is summarized in Figure 6. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 97 of 259 
 
Figure 6: 
Part E Dose Confirmation Scheme for TSR-042 and Carboplatin-Pemetrexed 
Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks. 
a Carboplatin-pemetrexed will be administered at the specified dose level as described in Table 6. In addition to receiving 
carboplatin-pemetrexed at the specified regimen, patients will be administered TSR-042 at 500 mg on Day 1 of every cycle 
Q3W.  
Recommended Phase 2 Dose for TSR-042 and Carboplatin-Pemetrexed 
The RP2D for TSR-042 and carboplatin-pemetrexed combination treatment will be confirmed 
following discussion and agreement between the Investigators and Sponsor based on evaluation 
of multiple endpoints, which may include the DLT rate in first and subsequent cycles of 
combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
Duration of Study Treatment 
Patients enrolled in Part E may continue TSR-042 and carboplatin-pemetrexed combination 
treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 and 
pemetrexed for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. Continued treatment with TSR-042 and 
pemetrexed beyond 2 years may be considered following discussion between the Sponsor and 
Investigator. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 98 of 259 
 
6.1.2.6. 
Part F: Safety and Tolerability for TSR-042, TSR-022, and Carboplatin-
Pemetrexed Combination Treatment 
Part F will begin after combination therapy in Part E has been determined as safe. Confirmation 
of the RP2D for TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment will be 
conducted using the dose levels described in Table 7. 
Table 7: 
Dose Regimen for TSR-042, TSR-022, and Carboplatin-Pemetrexed 
Combination Treatment 
Dose Level 
TSR-042 Dose 
TSR-022 Dose 
Pemetrexed Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of 
every cycle Q3W 
900 mg on Day 1 
Q3Wb 
500 mg/m2 Day 1 
Q3W (with vitamin 
supplementation) 
AUC of 5 or 6 on 
Day 1 Q3W 
administered for 4 
to 6 cycles as 
clinically indicated 
-1 
500 mg on Day 1 of 
every cycle Q3W 
300 mg on Day 1 
Q3Wb 
500 mg/m2 Day 1 
Q3W (with vitamin 
supplementation) 
AUC of 5 or 6 on 
Day 1 Q3W 
administered for 4 
to 6 cycles as 
clinically indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer 
therapies and pre-existing medical conditions. 
b 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available safety 
information, the Sponsor may decide to test additional dose levels of TSR-022. 
 
At dose level 1 (900 mg TSR-022), a cohort of 6 patients will be enrolled initially. After all 
patients in dose level 1 who are evaluable for safety have completed Cycle 1 of combination 
treatment, if ≤ 1 patient experiences a DLT (see DLT Assessment below), dose level 1 will be 
considered safe. If 2 of 6 patients experience DLTs, 6 additional patients will be enrolled at dose 
level 1. If ≤ 3 of 12 patients experience DLTs, dose level 1 will be considered safe. If ≥ 4 of 
12 patients experience DLTs at dose level 1, dose level -1 will enroll 6 patients. After all patients 
in dose level -1 who are evaluable for safety have completed Cycle 1 of combination treatment, 
if ≤ 1 patient experiences a DLT, dose level -1 will be considered safe. If 2 of 6 patients 
experience DLTs, 6 additional patients will be enrolled at dose level -1. If ≤ 3 of 12 patients 
experience DLTs, dose level -1 will be considered safe. The combination therapy, dose level -1, 
will be considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see 
Part F dose confirmation scheme below). However, when determining the RP2D, the Sponsor 
will review and consider safety data from all patients treated with the combination therapy. 
The Part F dose confirmation scheme is summarized in Figure 7. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 99 of 259 
 
Figure 7: 
Part F Dose Confirmation Scheme for TSR-042, TSR-022, and Carboplatin-
Pemetrexed Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity; Q3W = every 3 weeks. 
a Carboplatin-pemetrexed will be administered at the specified dose level as described in Table 7. In addition to 
receiving carboplatin-pemetrexed at the specified regimen, patients will be administered TSR-042 at 500 mg on 
Day 1 of every cycle Q3W and TSR-022 at 900 mg on Day 1 Q3W. 
b Patients at dose level -1 will be enrolled using the same 6 + 6 scheme used at dose level 1. 
 
Recommended Phase 2 Dose for TSR-042, TSR-022, and Carboplatin-Pemetrexed 
The RP2D for TSR-042, TSR-022, and combination treatment will be confirmed following 
discussion and agreement between the Investigators and Sponsor based on evaluation of multiple 
endpoints, which may include the DLT rate in first and subsequent cycles of combination 
treatment, the rate of dose modifications for non-DLT AEs, the ability to manage toxicities, PK, 
and signs of clinical efficacy. 
Duration of Study Treatment 
Patients enrolled in Part F may continue TSR-042, TSR-022, and carboplatin-pemetrexed 
combination treatment for 4 to 6 cycles, as indicated, after which, patients may continue 
TSR-042,TSR-022, and pemetrexed combination therapy for up to 2 years or until disease 
progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
Continued treatment with TSR-022, TSR-042, or pemetrexed beyond 2 years may be considered 
following discussion between the Sponsor and Investigator.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 100 of 259 
 
6.1.2.7. 
Part G: Safety and Tolerability for TSR-042 and Carboplatin–Nab-Paclitaxel 
Combination Treatment 
Confirmation of the RP2D for TSR-042 and carboplatin–nab-paclitaxel combination treatment 
will be conducted using the dose level described in Table 8. 
Table 8: 
Dose Regimen for TSR-042 and Carboplatin–Nab-Paclitaxel Combination 
Treatment 
Dose Level 
TSR-042 Dose 
Nab-Paclitaxel Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of every 
cycle Q3W 
100 mg/m2 on Days 1, 8, and 
15 (Q1W) of every 3-week 
cycle, administered for 4 to 6 
cycles as clinically indicated 
AUC of 5 or 6 on Day 1 
Q3W administered for 4 to 6 
cycles as clinically indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q1W = every week; 
Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer 
therapies and pre-existing medical conditions. 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 
who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient 
experiences a DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 
patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 
patients experience DLTs, dose level 1 will be considered safe. The combination therapy will be 
considered unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see Part G 
dose confirmation scheme below). However, when determining the RP2D, the Sponsor will 
review and consider safety data from all patients treated with the combination therapy.  
The Part G dose confirmation scheme is summarized in Figure 8. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 101 of 259 
 
Figure 8: 
Part G Dose Confirmation Scheme for TSR-042 and Carboplatin–
Nab-Paclitaxel Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatinnab-paclitaxel will be administered at the specified dose level as described in Table 8. In addition to 
receiving carboplatinnab-paclitaxel at the specified regimen, patients will be administered TSR-042 at 500 mg on 
Day 1 of every cycle (Q3W).  
Recommended Phase 2 Dose for TSR-042 and Carboplatin–Nab-paclitaxel 
The RP2D for TSR-042 and carboplatin–nab-paclitaxel combination treatment will be confirmed 
following discussion and agreement between the Investigators and Sponsor based on evaluation 
of multiple endpoints, which may include the DLT rate in first and subsequent cycles of 
combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
Duration of Study Treatment 
Patients enrolled in Part G may continue TSR-042 and carboplatin–nab-paclitaxel combination 
treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 
monotherapy for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. Continued treatment with TSR-042 beyond 2 years 
may be considered following discussion between the Sponsor and the Investigator.  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 102 of 259 
 
6.1.2.8. 
Part H: Safety and Tolerability for TSR-042, TSR-022, and Carboplatin–
Nab-Paclitaxel Combination Treatment 
Part H will begin after combination therapy in Part G has been determined as safe. Confirmation 
of the RP2D for TSR-042, TSR-022, and carboplatinnab-paclitaxel combination treatment will 
be conducted using the dose levels described in Table 9. 
Table 9: 
Dose Regimen for TSR-042, TSR-022, and Carboplatin–Nab-Paclitaxel 
Combination Treatment 
Dose 
Level 
TSR-042 Dose 
TSR-022 Dose 
Nab-Paclitaxel Dose 
Carboplatin Dosea 
1 
500 mg on Day 1 of 
every cycle Q3W 
900 mg on Day 1 
Q3Wb 
100 mg/m2 on Days 1, 
8, and 15 (Q1W) of 
every 3-week cycle, 
administered for 4 to 
6 cycles as clinically 
indicated 
AUC of 5 or 6 on Day 
1 Q3W administered 
for 4 to 6 cycles as 
clinically indicated 
-1 
500 mg on Day 1 of 
every cycle Q3W 
300 mg on Day 1 
Q3Wb 
100 mg/m2 on Days 1, 
8, and 15 (Q1W) of 
every 3-week cycle, 
administered for 4 to 
6 cycles as clinically 
indicated 
AUC of 5 or 6 on 
Day 1 Q3W 
administered for 4 to 6 
cycles as clinically 
indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q1W = every week; 
Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer 
therapies and pre-existing medical conditions. 
b 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available safety 
information, the Sponsor may decide to test additional dose levels of TSR-022. 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 
who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient 
experiences a DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 
patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 
patients experience DLTs, dose level 1 will be considered safe. If ≥ 4 of 12 patients experience 
DLTs at dose level 1, dose level -1 will enroll 6 patients. After all patients in dose level -1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient 
experiences a DLT, dose level -1 will be considered safe. If 2 of 6 patients experience DLTs, 
6 additional patients will be enrolled at dose level -1. If ≤ 3 of 12 patients experience DLTs, dose 
level -1 will be considered safe. The combination therapy, dose level -1, will be considered 
unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see Part H dose 
confirmation scheme below). However, when determining the RP2D, the Sponsor will review 
and consider safety data from all patients treated with the combination therapy.  
The Part H dose confirmation scheme is summarized in Figure 9.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 103 of 259 
 
Figure 9: 
Part H Dose Confirmation Scheme for TSR-042, TSR-022, and 
CarboplatinNab-Paclitaxel Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatinnab-paclitaxel will be administered at the specified dose level as described in Table 9. In addition to 
receiving carboplatinnab-paclitaxel at the specified regimen, patients will be administered TSR-042 at 500 mg on 
Day 1 of every cycle Q3W and TSR-022 at 900 mg on Day 1 Q3W. 
b Patients at dose level -1 will be enrolled using the same 6 + 6 scheme used at dose level 1. 
Recommended Phase 2 Dose for TSR-042, TSR-022, and Carboplatin–Nab-Paclitaxel 
The RP2D for TSR-042, TSR-022, and carboplatinnab-paclitaxel combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles 
of combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
Duration of Study Treatment 
Patients enrolled in Part H may continue TSR-042, TSR-022, and carboplatin–nab-paclitaxel 
combination treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 
and TSR-022 combination therapy for up to 2 years or until disease progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death. Continued treatment with TSR-022 
or TSR-042 beyond 2 years may be considered following discussion between the Sponsor and 
the Investigator.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 104 of 259 
 
6.1.2.9. 
Part I: Safety and Tolerability for TSR-042, TSR-022, and Carboplatin-
Paclitaxel Combination Treatment 
Confirmation of the RP2D for TSR-042, TSR-022, and carboplatin-paclitaxel combination 
treatment will be conducted using the dose levels described in Table 10. 
Table 10: 
Dose Regimen for TSR-042, TSR-022, and Carboplatin-Paclitaxel 
Combination Treatment 
Dose Level 
TSR-042 Dose 
TSR-022 Dose 
Carboplatin-Paclitaxel Dose 
1 
500 mg on Day 1 of every 
cycle Q3W 
900 mg on Day 1 Q3Wb 
Carboplatina AUC of 5 or 6 on Day 1 
Q3W and paclitaxel 175 mg/m2 on 
Day 1 Q3W administered for 4 to 
6 cycles as clinically indicated 
-1 
500 mg on Day 1 of every 
cycle Q3W 
300 mg on Day 1 Q3Wb 
Carboplatina AUC of 5 or 6 on Day 1 
Q3W and paclitaxel 175 mg/m2 on 
Day 1 Q3W administered for 4 to 
6 cycles as clinically indicated 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; Q3W = every 3 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer 
therapies and pre-existing medical conditions. 
b 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides 
maximal pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available safety 
information, the Sponsor may decide to test additional dose levels of TSR-022. 
At dose level 1, a cohort of 6 patients will be enrolled initially. After all patients in dose level 1 
who are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient 
experiences a DLT (see DLT Assessment below), dose level 1 will be considered safe. If 2 of 6 
patients experience DLTs, 6 additional patients will be enrolled at dose level 1. If ≤ 3 of 12 
patients experience DLTs, dose level 1 will be considered safe. If ≥ 4 of 12 patients experience 
DLTs in dose level 1, dose level -1 will enroll 6 patients. After all patients in dose level -1 who 
are evaluable for safety have completed Cycle 1 of combination treatment, if ≤ 1 patient 
experiences a DLT, dose level -1 will be considered safe. If 2 of 6 patients experience DLTs, 
6 additional patients will be enrolled at dose level -1. If ≤ 3 of 12 patients experience DLTs, dose 
level -1 will be considered safe. The combination therapy, dose level -1, will be considered 
unsafe if ≥3 of 6 or ≥4 of 12 patients experience DLTs during Cycle 1 (see Part I dose 
confirmation scheme below). However, when determining the RP2D, the Sponsor will review 
and consider safety data from all patients treated with the combination therapy.  
The Part I dose confirmation scheme is summarized in Figure 10. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 105 of 259 
 
Figure 10: 
Part I Dose Confirmation Scheme for TSR-042, TSR-022, and Carboplatin-
Paclitaxel Combination Treatment 
 
Abbreviations: DLT = dose-limiting toxicity. 
a Carboplatin-paclitaxel will be administered at the specified dose level as described in Table 10. In addition to 
receiving carboplatin-paclitaxel at the specified regimen, patients will be administered TSR-042 at 500 mg on 
Day 1 of every cycle Q3W and TSR-022 at 900 mg on Day 1 Q3W. 
b Patients at dose level -1 will be enrolled using the same 6 + 6 scheme used at dose level 1. 
Recommended Phase 2 Dose for TSR-042, TSR-022, and Carboplatin-Paclitaxel 
The RP2D for TSR-042, TSR-022, and carboplatin-paclitaxel combination treatment will be 
confirmed following discussion and agreement between the Investigators and Sponsor based on 
evaluation of multiple endpoints, which may include the DLT rate in first and subsequent cycles 
of combination treatment, the rate of dose modifications for non-DLT AEs, the ability to manage 
toxicities, PK, and signs of clinical efficacy. 
Duration of Study Treatment 
Patients enrolled in Part I may continue TSR-042, TSR-022, and carboplatin-paclitaxel 
combination treatment for 4 to 6 cycles, as indicated, after which patients may continue TSR-042 
and TSR-022 combination therapy for up to 2 years or until disease progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death. Continued treatment with TSR-022 
or TSR-042 beyond 2 years may be considered following discussion between the Sponsor and 
the Investigator.  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 106 of 259 
 
6.1.2.10. Dose-Limiting Toxicity Assessment 
DLTs will be assessed during Cycle 1 (i.e., during the first 21 days of treatment on Day 1 to 
Day 21). DLT criteria are as follows: 
 Any treatment-related Grade 4 nonhematologic clinical (nonlaboratory) AE 
 Any treatment-related Grade 3 nonhematologic clinical (nonlaboratory) AE lasting 
>3 days despite optimal medical intervention 
 Any treatment-related Grade 3 or 4 nonhematologic laboratory abnormality if any of 
the following also occur: 
 The abnormality leads to hospitalization. 
 The abnormality persists for ≥7 days from the time of AE onset and patient is 
symptomatic from the AE. 
 Any treatment-related hematologic toxicity defined as any of the following: 
 Grade 4 thrombocytopenia persists for ≥7 days from the time of AE onset or 
Grade 3 or 4 thrombocytopenia associated with clinically significant bleeding 
 Grade 4 neutropenia, Grade 3 or 4 neutropenia associated with infection, or Grade 
3 or 4 febrile neutropenia persists for ≥7 days 
 Grade 4 anemia or Grade 3 anemia requiring blood transfusion 
 Any treatment-related toxicity leading to prolonged delay (>2 weeks) in initiating 
Cycle 2 
 Any treatment-related Grade 5 AE 
A patient will be considered nonevaluable for DLTs if, for any reason other than safety, the 
patient is unable to complete the 21-day combination treatment DLT observation period or is 
unable to take >80% of the intended dose of either agent. For patients who skip niraparib doses 
due to hematologic AEs based on dose modification table (Table 13) which do not meet the DLT 
criteria, it is allowed to miss up to 10 days of niraparib during Cycle 1 to be considered as 
evaluable for DLTs. Patients considered nonevaluable may be replaced after consultation 
between the Sponsor and Investigator. 
Niraparib administration has been safely managed with dose interruptions or adjustments for 
AEs, including laboratory abnormalities, while maintaining activity in the single-agent setting. 
Therefore, niraparib dose interruption, dose reduction, or both, for an AE that does not meet a 
DLT definition as described above will be considered a non-DLT modification. Non-DLT dose 
modifications will be considered in determining the RP2D for TSR-042 and niraparib 
combination treatment. However, patients requiring a non-DLT dose modification that makes 
them unable to take >80% of the intended dose during Cycle 1 will be considered nonevaluable 
for DLTs. 
Appropriate dose modification of niraparib is described in Section 6.4.1.1. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 107 of 259 
 
6.2. 
Number of Subjects 
In Part A, approximately 12 to 24 patients will be enrolled.  
In Part B, approximately 12 patients will be enrolled. 
In Part C, approximately 6 to 24 patients may be enrolled. Dose level 1 will enroll 6 to 12 
patients. Dose level 2 is optional.  
In Part D, approximately 6 to 12 patients will be enrolled.  
In Part E, approximately 6 to 12 patients will be enrolled. 
In Part F, approximately 6 to 24 patients will be enrolled. 
In Part G, approximately 6 to 12 patients will be enrolled. 
In Part H, approximately 6 to 24 patients will be enrolled. 
In Part I, approximately 6 to 24 patients will be enrolled. 
6.3. 
Treatment Assignment 
6.3.1. 
Part A: Dose Finding for TSR-042 and Niraparib Combination Treatment 
An initial cohort of 6 to 12 patients will be enrolled at dose level 1 of TSR-042 and niraparib 
combination treatment, and dose escalation will be conducted as described in Section 6.1.2. Once 
dose level 1 is determined to be safe, an additional cohort of 6 to 12 patients will be enrolled at 
dose level 2.  
6.3.2. 
Part B: TSR-042 and Carboplatin-Paclitaxel Combination Treatment Safety and 
Tolerability 
A cohort of approximately 12 patients will be enrolled at dose level 1 in Part B. 
6.3.3. 
Part C: Dose Finding for TSR-042, Niraparib, and Bevacizumab Combination 
Treatment  
A cohort of approximately 6 to 12 patients will be enrolled at dose level 1 of TSR-042, niraparib, 
and bevacizumab combination treatment.  Dose level 2 is optional.  
6.3.4. 
Part D: TSR-042, Carboplatin-Paclitaxel, and Bevacizumab Combination 
Treatment 
A cohort of approximately 6 to 12 patients will be enrolled at dose level 1 in Part D.  
6.3.5. 
Part E: TSR-042 and Carboplatin-Pemetrexed Combination Treatment 
A cohort of approximately 6 to 12 patients will be enrolled at dose level 1 in Part E.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 108 of 259 
 
6.3.6. 
Part F: TSR-042, TSR-022, and Carboplatin-Pemetrexed Combination 
Treatment 
A cohort of approximately 6 to 12 patients will be enrolled at dose level 1 in Part F. If dose 
level 1 is determined to be not safe, an additional cohort of 6 to 12 patients will be enrolled at 
dose level -1. 
6.3.7. 
Part G: TSR-042 and Carboplatin–Nab-Paclitaxel Combination Treatment 
A cohort of approximately 6 to 12 patients will be enrolled at dose level 1 in Part G.  
6.3.8. 
Part H: TSR-042, TSR-022, and Carboplatin–Nab-Paclitaxel Combination 
Treatment 
A cohort of approximately 6 to 12 patients will be enrolled at dose level 1 in Part H. If dose 
level 1 is determined to be not safe, an additional cohort of 6 to 12 patients will be enrolled at 
dose level -1. 
6.3.9. 
Part I: TSR-042, TSR-022, and Carboplatin-Paclitaxel Combination Treatment 
A cohort of approximately 6 to 12 patients will be enrolled at dose level 1 in Part I. If dose 
level 1 is determined to be not safe, an additional cohort of 6 to 12 patients will be enrolled at 
dose level -1. 
6.4. 
Dose Adjustment Criteria 
Study treatment dosing interruptions are permitted in the case of medical and/or surgical events 
or logistical reasons not related to study treatment (e.g., surgery, unrelated medical events, 
patient vacation, and/or holidays). Patients should be placed back on study treatment within ≤28 
days of the scheduled interruption, unless otherwise discussed with the Sponsor. 
All treatment interruptions and dose reductions (including any missed doses), and the reasons for 
the reductions/interruptions, are to be recorded in the electronic case report form (eCRF). 
6.4.1. 
Safety Criteria for Adjustment or Stopping Doses 
6.4.1.1. 
Niraparib 
Intrapatient Dose Escalation 
After Cycle 2, the dose of niraparib may be increased to a higher dose level that has been found 
to be safe during the dose-escalation phase following discussion with the Sponsor.  
Niraparib Dose Interruption and Modification 
Treatment must be interrupted for any nonhematologic Common Terminology Criteria for 
Adverse Events (CTCAE) Grade 3 or 4 AE that the Investigator considers to be related to 
administration of niraparib (Table 11). If the nonhematologic toxicity is appropriately resolved to 
baseline or Grade ≤1 within 4 weeks (28 days) of the dose interruption period, the patient may 
restart treatment with niraparib but with a dose level reduction if prophylaxis is not considered 
feasible (see Table 12). If the event recurs at similar or worse grade, treatment should be 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 109 of 259 
 
interrupted again and, upon resolution, a further dose reduction must be made. No more than 
2 dose reductions will be permitted (i.e., to a minimum dose of 100 mg QD).  
If the toxicity requiring dose interruption has not resolved completely or to CTCAE Grade 1 
during the maximum 4-week (28-day) dose interruption period, and/or the patient has already 
undergone a maximum of 2 dose reductions (to a minimum dose of 100 mg QD), the patient 
must permanently discontinue treatment with niraparib. 
The dose interruption and modification criteria for niraparib for hematologic parameters will be 
based on blood counts and are outlined in Table 13. If the hematologic toxicity has not recovered 
to the specified levels within 4 weeks (28 days) of the dose interruption period, and/or the patient 
has already undergone a maximum of 2 dose reductions (to a minimum dose of 100 mg QD), the 
patient must permanently discontinue treatment with niraparib. 
Table 11: 
Niraparib Dose Modifications for Nonhematologic Adverse Reactions 
Abnormality 
Intervention 
Non-hematologic CTCAE ≥ Grade 3 adverse reaction 
where prophylaxis is not considered feasible or adverse 
reaction persists despite treatment 
Withhold niraparib for a maximum of 28 days or until 
resolution of adverse reaction. 
Resume niraparib at a reduced dose. Up to 2 dose 
reductions are permitted. 
CTCAE ≥ Grade 3 treatment-related adverse reaction 
lasting more than 28 days while patient is administered 
niraparib 100 mg/day 
Discontinue niraparib. 
Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events. 
 
Table 12: 
Niraparib Dose Reductions for Nonhematologic Toxicity 
Event 
Dosea 
Initial dose 
300b mg QD 
First dose reduction for treatment-related CTCAE Grade 3 or 4 AE or SAE where 
prophylaxis is not considered feasible 
200 mg QD 
Second dose reduction for treatment-related CTCAE Grade 3 or 4 AE or SAE where 
prophylaxis is not considered feasible 
100 mg QD 
Continued treatment-related CTCAE Grade 3 or 4 AE or SAE lasting >28 days 
Discontinue niraparib 
Abbreviations: AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; QD = once 
daily; SAE = serious adverse event. 
a Dose not to be decreased below 100 mg daily. 
b If the initial dose is below 300 mg, the same dose reduction principles will apply with fewer dose modification 
steps available. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 110 of 259 
 
Table 13: 
Niraparib Dose Modifications for Hematologic Toxicity 
Laboratory Abnormality 
Intervention 
Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and 
periodically after this time. 
Platelet count < 100,000/μL 
First occurrence: 
Withhold niraparib for a maximum of 28 days and monitor blood counts 
weekly until platelet counts return to ≥100,000/μL. 
Resume niraparib at same or reduced dose.a 
If platelet count is < 75,000/μL, resume niraparib at a reduced dose 
Second occurrence: 
Withhold niraparib for a maximum of 28 days and monitor blood counts 
weekly until platelet counts return to ≥100,000/μL. 
Resume niraparib at a reduced dose.a 
Discontinue niraparib if the platelet count has not returned to acceptable 
levels within 28 days of the dose interruption period, or if the patient has 
already undergone dose reduction to 100 mg QD. 
Neutrophil count < 1,000/μL 
Withhold niraparib for a maximum of 28 days and monitor blood counts 
until neutrophil counts return to ≥1,500/μL.  
Resume niraparib at a reduced dose.a 
Discontinue niraparib if neutrophil level has not returned to acceptable 
levels within 28 days of the dose interruption period, or if the patient has 
already undergone dose reduction to 100 mg QD. 
Hemoglobin ≤ 8 g/dL 
Withhold niraparib for a maximum of 28 days and monitor blood counts 
until hemoglobin returns to ≥9 g/dL.  
Resume niraparib at a reduced dose.a 
Discontinue niraparib if hemoglobin has not returned to acceptable 
levels within 28 days of the dose interruption period, or if the patient has 
already undergone dose reduction to 100 mg QD. 
Hematologic adverse reaction 
requiring transfusion 
For patients with platelet count ≤10,000/μL, platelet transfusion should 
be considered. If there are other risk factors such as co-administration of 
anticoagulation or antiplatelet drugs, consider interrupting these drugs 
and/or transfusion at a higher platelet count. 
Resume niraparib at a reduced dose.a 
Confirmed diagnosis of MDS or 
AML 
Permanently discontinue niraparib. 
Abbreviation: AML = acute myeloid leukemia; MDS = myelodysplastic syndrome; QD = once daily.  
a Niraparib dose must not be decreased below 100 mg daily. Additional details on dose reduction are described in 
Table 12.  
In the case of thrombocytopenia, following the first occurrence, resumption of therapy may 
occur at the same dose or 1 dose level lower when the hematologic toxicity has resolved. 
Subsequent occurrences should trigger dose reduction upon resumption of therapy. If the platelet 
count has not reverted within 28 days of interruption to ≥100,000/μL, then study treatment 
should be discontinued. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 111 of 259 
 
If dose interruption and/or modification is required at any point during study treatment because 
of hematologic toxicity, weekly blood draws for complete blood count (CBC) will be monitored 
until the AE resolves to the specified blood count levels. To ensure the safety of the new dose, 
weekly blood draws for CBC will be required for an additional 4 weeks after the AE has 
resolved, after which monitoring every 4 weeks may resume. CBC monitoring will continue 
every 4 weeks (i.e., monthly) for the next 11 months of treatment, and periodically after this 
time. 
Any patient requiring transfusion of platelets or red blood cells (≥1 unit) must undergo a dose 
reduction upon recovery if study treatment is resumed. 
If a diagnosis of MDS/AML is confirmed by a hematologist, the patient must permanently 
discontinue study treatment. 
For major surgery while on study treatment, up to 4 weeks (28 days) of study treatment 
interruption is allowed.  
Once the dose of study treatment has been reduced, any re-escalation must be discussed with the 
Sponsor’s Medical Monitor. 
All dose interruptions and reductions (including any missed doses), and the reasons for the 
reductions/interruptions, are to be recorded in the eCRF. Reasons for the discontinuation of 
niraparib must also be recorded in the eCRF. 
6.4.1.2. 
TSR-042 and TSR-022 
AEs (both nonserious and serious) associated with TSR-042 or TSR-022 exposure may represent 
an immunologic etiology. These AEs may occur shortly after the first dose or several months 
after the last dose of treatment. 
In general, TSR-042 and TSR-022 must be withheld for drug-related Grade 3 toxicities, as well 
as for certain immune-related adverse events of interest (irAEIs), but may be resumed upon 
recovery to Grade ≤1; TSR-042 and/or TSR-022 will be permanently discontinued for any drug-
related Grade 4 AE. TSR-042 and/or TSR-022 must be permanently discontinued for certain 
irAEIs as described in Table 14. The recent joint American Society of Clinical Oncology 
(ASCO) and NCCN guideline for diagnosis and management of immune-related adverse events 
treated with immune checkpoint inhibitor therapy107 may be used as a supplement to Table 14. 
The specific immune-related AEs typically observed with anti-PD-1 antibodies will be managed 
according to the guidelines summarized below.108  
The reason for interruption or discontinuation of TSR-042 and/or TSR-022 should be recorded in 
the eCRF. 
Immune-related Adverse Events of Interest and Guidelines for Management 
Given the mechanisms of action of TSR-042 and TSR-022, it is anticipated that activation of 
cellular immune system can be manifested as immune-related AEs. Based on available safety 
data from checkpoint inhibitors, TEAEs with the specific grades listed below were selected as 
irAEIs. The list of irAEIs may be updated upon emerging data. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 112 of 259 
 
Refer to Table 14 for details on the management of TSR-042 and/or TSR-022 dose delays and 
discontinuation for specific irAEIs. Detailed guidance for the administration of rescue 
medications and supportive care is available in Section 9.7.4. For all irAEIs listed in Table 14, 
TSR-042 and/or TSR-022 should be withheld until the patient is clinically and metabolically 
stable and AEs have resolved to Grade ≤1. If systemic steroids are used as a part of irAEI 
management, the total dose of daily steroids should be equal to or less than prednisone 10 mg at 
the time of resuming TSR-042 and/or TSR-022. 
All treatment delays (including any missed doses) and discontinuations, and the reason for delays 
or discontinuation of TSR-042 and/or TSR-022, should be recorded in the eCRF. 
Table 14: 
Guidelines for Treatment of Immune-related Adverse Events of Interest 
Toxicity 
Hold Treatment For 
Grade 
Restarting Treatment/ discontinuation 
Diarrhea/colitis 
2-3 
Restart dosing when toxicity resolves to Grade 0-1. 
4 
Permanently discontinue. 
AST, ALT, or 
increased 
bilirubin 
2 
(AST or ALT > 3 and ≤ 5 × 
ULN or  
total bilirubin > 1.5 and ≤ 3 
× ULN) 
Restart dosing when toxicity resolves to Grade 0-1. 
3-4 
(AST or ALT > 5 × ULN  
or total bilirubin > 3 × 
ULN)  
Permanently discontinue (see exception below)a 
Type 1 diabetes 
mellitus (TIDM) 
or hyperglycemia 
3-4 hyperglycemia or 
T1DM (associated with 
metabolic acidosis or 
ketonuria) 
Restart dosing in appropriately managed, clinically 
and metabolically stable patients, insulin 
replacement therapy is required. 
Immune-related 
Encephalitis  
Any grade 
Permanently discontinue. 
Hypophysitis 
2-4 
For Grade 2-3 hold until hormonal therapy results in 
return to adequate levels by laboratory values and 
restart dosing when toxicity resolves to Grade 0-1. 
For recurrence or worsening of ≥ Grade 2 
hypophysitis after steroid taper has been completed 
and is on adequate hormone replacement therapy, 
permanently discontinue. For Grade 4, permanently 
discontinue. 
Adrenal 
insufficiency 
2-3 
Hold until hormonal therapy results in return to 
adequate levels by laboratory values and restart 
dosing when toxicity resolves to Grade 0-1. For 
recurrent or worsening ≥Grade 2 adrenal 
insufficiency while adequate hormonal replacement 
is continuing, permanently discontinue study drug. 
4 
Permanently discontinue.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 113 of 259 
 
Table 14: 
Guidelines for Treatment of Immune-related Adverse Events of Interest 
(Continued) 
Toxicity 
Hold Treatment For 
Grade 
Restarting Treatment/ discontinuation 
Hypo- and 
hyperthyroidism  
3 
Hold until hormonal therapy results in return to 
adequate levels by laboratory values and restart 
dosing when toxicity resolves to Grade 0-1. 
4 
Permanently discontinue. 
Infusion-related 
reaction 
2b 
Restart dosing when toxicity resolves to Grade 0-1. 
3-4 
Permanently discontinue. 
Pneumonitis 
2 
Restart dosing when toxicity resolves to Grade 0-1. 
If Grade 2 recurs, permanently discontinue. 
3-4 
Permanently discontinue. 
Rash 
3 
Restart dosing when toxicity resolves to Grade 0-1 
4 
Permanently discontinue 
Renal failure or 
nephritis 
2 
Restart dosing when toxicity resolves to Grade 0-1. 
3-4 
Permanently discontinue. 
Recurrence of 
AEs after 
resolution to ≤ 
Grade 1 
3-4 
Permanently discontinue. 
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; T1DM = 
type 1 diabetes mellitus; ULN = upper limit of normal. 
a  For patients with liver metastasis who begin treatment with Grade 2 AST or ALT, if AST or ALT increases by 
≥50% relative to baseline and lasts for at least 1 week, then study treatment should be discontinued. 
b Upon resolution within 1 hour of stopping drug infusion, the infusion may be restarted at 50% of the original 
infusion rate (e.g., from 100 to 50 mL/h). Otherwise, study treatment will be withheld until symptoms resolve, and 
the patient should be premedicated for the next scheduled dose; refer to Section 9.7.4 for further management 
details. 
6.4.1.3. 
Carboplatin-Paclitaxel 
Hematological and nonhematological AEs attributable to carboplatin and/or paclitaxel will be 
managed as indicated in the labeling information and by local institutional practice. 
6.4.1.4. 
Carboplatin-Pemetrexed 
Hematological and nonhematological AEs attributable to carboplatin and/or pemetrexed will be 
managed as indicated in the labeling information and by local institutional practice. 
6.4.1.5. 
Carboplatin–Nab-Paclitaxel 
Hematological and nonhematological AEs attributable to carboplatin and/or nab-paclitaxel will 
be managed as indicated in the labeling information and by local institutional practice. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 114 of 259 
 
6.4.1.6. 
Bevacizumab 
Hematological and nonhematological AEs attributable to carboplatin and/or nab-paclitaxel will 
be managed as indicated in the labeling information and by local institutional practice. Dose 
reductions of bevacizumab are not permitted in this study.109,110  
Interrupt bevacizumab treatment for the following adverse events: proteinuria, medically 
significant hypertension that cannot be adequately controlled with antihypertensive therapy, 
hypertension in the presence of posterior reversible encephalopathy syndrome, development of 
hypertensive crisis or hypertensive encephalopathy, or nephrotic syndrome. In case of 
uncontrolled hypertension, niraparib should also be held in addition to bevacizumab.  
Resume bevacizumab treatment only when 1) hypertension is controlled by hypertensive 
regimen, or 2) urine protein is < 2 g per 24 hours urine collection.103 Niraparib should be 
resumed with bevacizumab when hypertension is controlled by hypertensive regimen. If 
hypersensitivity or infusion reactions occur during bevacizumab infusion, the infusion should be 
discontinued. Except in cases where permanent discontinuation of bevacizumab is indicated, 
resumption of the standard dose of bevacizumab upon resolution of other adverse reactions is at 
the discretion of the investigator. 
Bevacizumab treatment should be withheld 4 weeks prior to elective surgery. In patients who 
experience wound healing complications during the study, treatment with bevacizumab should 
be withheld until the wound is fully healed.   
 
Pharmacokinetic Criteria for Adjustment or Stopping Doses 
Not applicable. 
6.5. 
Criteria for Study Termination 
The Sponsor may terminate this study at any time. The Sponsor will notify Investigators when 
the study is to be placed on hold, completed, or terminated. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 115 of 259 
 
7. 
STUDY POPULATION 
7.1. 
Inclusion Criteria 
Patients will be eligible for study entry if all of the following criteria are met: 
1. Patient is male or female and at least 18 years of age.  
2. Patient has histologically or cytologically proven advanced (unresectable) or metastatic 
cancer as outlined below according to study part and disease type: 
a. Part A: Patients with previously treated advanced or metastatic cancer. Patient may 
have received no more than 4 lines of treatment for advanced or metastatic cancer. 
Hormonal treatment will not be considered a prior line of treatment. 
b. Part B: Patients with advanced or metastatic cancer for which treatment with 
carboplatin-paclitaxel is considered appropriate therapy. Patient may have received 
no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal 
treatment will not be considered a prior line of treatment.  
c. Part C: Patients with previously treated advanced or metastatic cancer. Patient may 
have received no more than 4 lines of treatment for advanced or metastatic cancer. 
Hormonal treatment will not be considered a prior line of treatment. 
d. Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered 
appropriate therapy. Patient may have received no more than 1 prior line of 
chemotherapy in the metastatic setting. Hormonal treatment will not be considered a 
prior line of treatment. 
e. Parts E, F, G, H, I: Patients who have not received prior systemic therapy, including 
targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or 
IV) NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible 
as long as development of advanced or metastatic disease occurred at least 12 months 
after completion of neoadjuvant or adjuvant therapy. 
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 
of 0 to 1. 
4. Patient has adequate organ function defined as follows (Note: CBC test should be 
obtained without transfusion or receipt of colony-stimulating factors in the 2 weeks 
before obtaining sample): 
a. Absolute neutrophil count ≥ 1,500/μL 
b. Platelets ≥ 100,000/μL 
c. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L 
d. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine 
clearance ≥ 50 mL/min using Cockcroft-Gault equation for patients with creatinine 
levels > 1.5 × institutional ULN 
e. Total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ 1 × ULN 
f. AST and ALT ≤ 2.5 × ULN unless liver metastases are present, in which case they 
must be ≤5 × ULN 
g. International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN unless the 
patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time 
(PTT) is within therapeutic range of intended use of anticoagulants 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 116 of 259 
 
h. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless the patient is 
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of 
intended use of anticoagulants 
5. Female patient has a negative serum pregnancy test within 72 hours prior to taking study 
treatment if of childbearing potential and agrees to abstain from activities that could 
result in pregnancy from screening through 180 days after the last dose of study 
treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as 
follows (by other than medical reasons): 
a. ≥45 years of age and has not had menses for >1 year 
b. Patients who have been amenorrheic for <2 years without history of a hysterectomy 
and oophorectomy must have a follicle stimulating hormone value in the 
postmenopausal range upon screening evaluation 
c. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented 
hysterectomy or oophorectomy must be confirmed with medical records of the actual 
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with 
medical records of the actual procedure, otherwise the patient must be willing to use 
effective contraception throughout the study, starting with the screening visit through 
180 days after the last dose of study treatment. See Section 9.7.3 for a list of 
acceptable birth control methods. Information must be captured appropriately within 
the site’s source documents. Note: Abstinence is acceptable if this is the established 
and preferred contraception for the patient. 
6. Male patient agrees to use an adequate method of contraception (see Section 9.7.3 for a 
list of acceptable birth control methods) and not donate sperm starting with the first dose 
of study treatment through 90 days after the last dose of study treatment. Note: 
Abstinence is acceptable if this is the established and preferred contraception for the 
patient. 
7. Patient has measurable lesions by RECIST v1.1. 
For Parts A and C, in addition to the general inclusion criteria, patients must also meet the 
following additional criteria to be considered eligible to participate in this study: 
8. Patient is able to take oral medications. 
9. For patients to be eligible for any parts of the study using niraparib 300 mg as a starting 
dose, a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 u/L 
is necessary. 
7.2. 
Exclusion Criteria 
Patients will not be eligible for the study entry if any of the following criteria are met: 
1. Patient has known active central nervous system metastases, carcinomatous meningitis, 
or both. Note: Patients with previously treated brain metastases may participate provided 
they are stable (without evidence of progression by imaging [using the identical imaging 
modality for each assessment, either magnetic resonance imaging [MRI] or computer 
tomography [CT] scan] for at least 4 weeks prior to the first dose of study treatment and 
any neurologic symptoms have returned to baseline), have no evidence of new or 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 117 of 259 
 
enlarging brain metastases, and have not been using steroids for at least 7 days prior to 
study treatment. Carcinomatous meningitis precludes a patient from study participation 
regardless of clinical stability. 
2. Patient has a known additional malignancy that progressed or required active treatment 
within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell 
carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical 
cancer. 
3. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, 
nonmalignant systemic disease, or active infection that requires systemic therapy. 
Specific examples include, but are not limited to, history of (noninfectious) pneumonitis 
that required steroids or current pneumonitis, uncontrolled ventricular arrhythmia, recent 
(within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable 
spinal cord compression, superior vena cava syndrome, or any psychiatric or substance 
abuse disorders that would interfere with cooperation with the requirements of the study 
(including obtaining informed consent). 
4. Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia), 
therapy, or laboratory abnormality that might confound the study results or interfere with 
the patient’s participation for the full duration of the study treatment including the 
following:  
a. Patients who received a transfusion (platelets or red blood cells) within 6 weeks of the 
first dose of study treatment are not eligible. 
b. Patients who received colony-stimulating factors (e.g., granulocyte colony-
stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant 
erythropoietin) within 4 weeks prior to the first dose of study treatment are not 
eligible.  
5. Patient is pregnant or expecting to conceive children within the projected duration of the 
study, starting with the screening visit through 180 days after the last dose of study 
treatment.  
a. No data are available regarding the presence of niraparib or its metabolites in human 
milk, or on its effects on the breastfed infant or milk production. Because of the 
potential for serious adverse reactions in breastfed infants from niraparib, female 
patients should not breastfeed during treatment with niraparib and for 1 month after 
receiving the final dose. 
6. Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or 
any other form of immunosuppressive therapy within 7 days prior to the first dose of 
study treatment. 
7. Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies). 
8. Patient has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) 
or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected). 
9. Patient has an active autoimmune disease that has required systemic treatment in the past 
2 years (i.e., with use of disease-modifying agents, corticosteroids, or 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 118 of 259 
 
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not 
considered a form of systemic treatment. 
10. Patient has not recovered (i.e., to Grade ≤1 or to baseline) from cytotoxic therapy-
induced AEs. Note: Patients with Grade ≤2 neuropathy, Grade ≤2 alopecia, or Grade ≤2 
fatigue are an exception to this criterion and may qualify for the study. 
11. Patient is currently participating and receiving study treatment or has participated in a 
study of an investigational agent and received study treatment or used an investigational 
device within 4 weeks of the first dose of treatment. 
12. Patient has had a prior cytotoxic therapy, anticancer targeted small molecules 
(e.g., tyrosine kinase inhibitors), hormonal agents within 5 half-lives, or monoclonal 
antibodies within 5 half-lives or 4 weeks (whichever is shorter) of that treatment prior to 
Day 1; radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any 
radiation therapy within 1 week prior to Day 1. 
13. Patient has not recovered adequately from AEs or complications from any major surgery 
prior to starting therapy. 
14. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, 
anti-CTLA-4 (including ipilimumab), or any other antibody or drug specifically targeting 
T-cell co-stimulation or checkpoint pathways. 
15. Patient has received a live vaccine within 14 days of planned start of study treatment.  
16. Patient has a heart-rate QTc prolongation >480 ms at screening. Note: If a patient has a 
prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon 
Investigator evaluation (i.e., the patient otherwise has no cardiac abnormalities), the 
patient may be eligible to participate in the study following discussion with the Sponsor’s 
Medical Monitor. 
17. Patient has a known hypersensitivity to TSR-042 components or excipients. 
For Parts A and C only, patients will not be eligible for study entry if any of the following 
additional exclusion criteria are met: 
18. Patient has undergone prior treatment with a known PARP inhibitor. 
19. Patient has a known hypersensitivity to niraparib components or excipients. 
20. Patient has had any known Grade 3 or 4 anemia, neutropenia, or thrombocytopenia due to 
prior chemotherapy that persisted >4 weeks related to the most recent prior treatment. 
21. Known history or current diagnosis of MDS or AML, or current diagnosis of prostate 
cancer. 
For Parts B, D, E, F, G, H, and I, patients will not be eligible for study entry if any of the 
following additional exclusion criterion are met: 
22. Patient has a known hypersensitivity to any of the following relevant study treatments: 
carboplatin, paclitaxel, pemetrexed, nab-paclitaxel, or TSR-022 components or 
excipients. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 119 of 259 
 
For Parts C and D only, patients will not be eligible for study entry if the following additional 
exclusion criterion is met: 
23. Patient has clinically significant cardiovascular disease (e.g., significant cardiac 
conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac 
arrhythmia or unstable angina, New York Heart Association Grade 2 or greater 
congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or 
greater peripheral vascular disease, and history of cerebrovascular accident [CVA]) 
within 6 months of enrollment. 
24. Patient has a history of bowel obstruction, including subocclusive disease, related to the 
underlying disease and history of abdominal fistula, gastrointestinal perforation, or 
intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination 
or bowel involvement on CT scan or clinical symptoms of bowel obstruction. 
25. Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening 
or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick 
at baseline should undergo 24-hour urine collection and must demonstrate <2 g of protein 
in 24 hours to be eligible). 
26. Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or 
surgery within the past 28 days prior to start of study treatment, history of hemorrhagic 
stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant 
hemorrhage within the past 3 months). 
27. Patient has a known hypersensitivity to bevacizumab components or excipients 
For Parts E and F only, patients will not be eligible for study entry if any of the following 
additional exclusion criteria are met: 
28. Patient is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs, other 
than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long -acting 
agents, such as piroxicam. 
29. Patient is unable or unwilling to take folic acid, vitamin B12 supplement. 
30. Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable 
following treatment for these conditions (including therapeutic thoraco- or paracentesis) 
is eligible. 
For Parts G, H, and I only, patients will not be eligible for study entry if any of the following 
additional exclusion criteria are met: 
31. Patient has pre-existing peripheral neuropathy that is Grade ≥ 2 by Common 
Terminology Criteria for Adverse Events (CTCAE) version 4 criteria. 
32. Patient has interstitial lung disease or a history of pneumonitis that required oral or 
intravenous glucocorticoids to assist with management. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 120 of 259 
 
7.3. 
Patient Discontinuation and Replacement 
7.3.1. 
Discontinuation from Study Treatment  
Patients may be discontinued from study treatment at any time. Specific examples of reasons for 
discontinuing all study treatments are listed below: 
 AE 
 Disease progression as outlined in Section 10.1 or based on clinical criteria by 
Investigator 
 Risk to patient as judged by the Investigator and/or Sponsor 
 Severe noncompliance with the protocol as judged by the Investigator and/or Sponsor 
 Patient request 
 Patient becomes pregnant 
 Sponsor decision to terminate study 
 Death 
Discontinuation of treatment may be considered for patients who have attained a confirmed 
complete response (CR), have been treated for at least 24 weeks with study treatments, and had 
at least 2 cycles of treatment beyond the date when the initial CR was declared. 
Details of required niraparib dose modifications, including interruptions, dose reductions, and 
permanent discontinuations, related to toxicity are provided in Section 6.4.1.1. Details of 
required TSR-042 and TSR-022 dose interruptions and permanent discontinuation related to 
toxicity are provided in Section 6.4.1.2. Details of required carboplatin-paclitaxel dose 
interruptions and permanent discontinuation related to toxicity are provided in Section 6.4.1.3. 
Details of required carboplatin-pemetrexed dose interruptions and permanent discontinuation 
related to toxicity are provided in Section 6.4.1.4. Details of required carboplatin–nab-paclitaxel 
dose interruptions and permanent discontinuation related to toxicity are provided in 
Section 6.4.1.5. Details of required bevacizumab dose interruptions and permanent 
discontinuation related to toxicity are provided in Section 6.4.1.6. 
If a patient must stop a study drug other than TRS-042 or TSR-022 due to toxicity after Cycle 1 
(see Section 6.4.1), the patient will be allowed to continue TSR-042 or TSR-022 if the criteria 
listed below are met:  
1. The patient is receiving clinical benefit from study treatment. 
2. The AE that led to discontinuation of a study drug is not related to TSR-042 or TSR-022 
in the judgement of the investigator. 
Patients who discontinue from all study treatments will continue to receive follow-up 
assessments [see Table 18 (Part A), Table 20 (Part B), Table 22 (Part C), Table 24 (Part D), 
Table 26 (Part E), Table 28 (Part F), Table 30 (Part G), Table 32 (Part H), and Table 34 (Part I)], 
as part of the study unless they are discontinued from the study (Section 7.3.2). 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 121 of 259 
 
7.3.2. 
Discontinuation from the Study 
Patients may be discontinued from the study for any of the following reasons: 
 Withdrawal of consent by the patient, who is at any time free to discontinue their 
participation in the study, without prejudice to further treatment 
 Loss to follow-up 
 Death from any cause 
 Sponsor’s decision to terminate study 
 Investigator’s decision 
If a patient is thought to be lost to follow-up, discontinues study treatment, or discontinues the 
study, attempts should be made to contact the patient to determine the reason for discontinuation. 
For patients who are lost to follow-up, at least 3 documented attempts, including 1 via certified 
mail, should be made to contact the patient before the patient is deemed lost to follow-up. 
7.3.3. 
Replacement of Patients 
After consultation between the Sponsor and the Investigator, enrollment may be extended to 
replace patient(s) who become non-evaluable for safety during Parts A, B, C, D, E, F, G, H, or I. 
7.4. 
Patient Identification and Randomization 
7.4.1. 
Patient Identification 
All patients who enter into the Screening Period of the study (defined as the point at which the 
patient signs the informed consent form [ICF]) will receive a unique patient identification 
number. This number will be used to identify the patient throughout the study and must be used 
on all study documentation related to that patient. A patient will be considered enrolled when the 
patient has been consented and screened and when all eligibility criteria have been confirmed in 
the eCRF. The patient identification number must remain constant throughout the entire study; it 
must not be changed at the time of enrollment. 
7.4.2. 
Randomization Scheme 
Not applicable. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 122 of 259 
 
8. 
TREATMENT OF PATIENTS 
8.1. 
Description of Study Drug 
Table 15: 
Investigational Product 
Parameter 
Investigational 
Product 
 
 
 
 
 
 
 
Product name 
TSR-042 
Niraparib 
Carboplatin
a 
Paclitaxel 
Pemetrexed 
Nab-Paclitaxel 
Bevacizumab 
TSR-022
b 
Dosage form 
Infusion 
Capsule 
Infusion 
Infusion 
Infusion 
Infusion 
Infusion 
Infusion 
Duration of 
infusion 
30 minutes 
NA 
30 or 60 
minutes 
(30 minutes 
preferred) 
3 hours 
10 minutes 
30 minutes 
Based on 
local 
approved 
product label 
30 minutes 
Unit dose 
 500 mg on Day 1 
of every cycle 
Q3W (first 
4 cycles), 
followed by 1,000 
mg on Day 1 of 
every other cycle 
(Q6W) beginning 
on Day 1/Cycle 5 
for Parts A, B, C, 
and D. 
 500 mg on Day 1 
of every cycle 
Q3W for Parts E, 
F, G, H, and I 
Dose level 1: 
200 mg on 
Days 1 to 21 
Q3W 
thereafter 
AUC of 5 or 6 
on Day 1 
Q3W 
administered 
for 4 to 6 
cycles as 
clinically 
indicated 
175 mg/m2 
on Day 1 
Q3W 
administered 
for 4 to 6 
cycles as 
clinically 
indicated 
500 mg/m2 
Day 1 Q3W 
(with vitamin 
supplementation) 
 
100 mg/m2 on 
Days 1, 8, and 
15 (Q1W) of 
every 3-week 
cycle, 
administered 
for 4 to 6 
cycles as 
clinically 
indicated  
15 mg/kg on 
Day 1 Q3W 
for up to 15 
months 
Dose Level 
1: 
900 mg 
Day 1 Q3W  
Dose level 2: 
300 mg on 
Days 1 to 21 
Q3W 
thereafter 
Dose 
level -1: 
300 mg 
Day 1 Q3W  
 
Route of 
administration 
IV 
PO 
IV 
IV 
IV 
IV 
IV 
IV 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; NA = not applicable; PO = orally; Q1W = every week; 
Q3W = every 3 weeks; Q6W = every 6 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical 
conditions. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 123 of 259 
 
b 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides maximal pharmacodynamic effect; this dose may 
be lowered to dose level -1 if needed. Based on available safety information, the Sponsor may decide to test additional dose levels of TSR-022. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 124 of 259 
 
9. 
STUDY DRUG MATERIALS AND MANAGEMENT 
9.1. 
Identity 
9.1.1. 
Niraparib 
Niraparib ([3S]-3-[4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl] piperidine [tosylate 
monohydrate salt]) is an orally available, potent, highly selective PARP1 and PARP2 inhibitor. 
The excipients for niraparib are lactose monohydrate and magnesium stearate. Niraparib will be 
supplied as 100-mg capsules. 
9.1.2. 
TSR-042 
TSR-042 is an IgG4-κ humanized monoclonal antibody and will be supplied as a solution in 
vials containing 160 mg or 500 mg (20 mg/mL or 50 mg/mL, respectively). 
9.1.3. 
TSR-022 
TSR-022 is a humanized monoclonal IgG4 antibody and will be supplied as a solution in vials 
containing 160 mg (20 mg/mL).  
9.1.4. 
Carboplatin-Paclitaxel 
9.1.4.1. 
Carboplatin 
Carboplatin (platinum, diamine [1,1-cyclobutanedicarboxylato(2-)-O,O’]-,(SP-4-2)) is a 
platinum coordination compound and will be supplied as a sterile, pyrogen-free, 10 mg/mL 
aqueous solution for infusion. 
9.1.4.2. 
Paclitaxel 
Paclitaxel (5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 
2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine) is a natural product with 
antitumor activity, derived from Taxus baccata. 
Paclitaxel for injection is a clear, colorless to slightly yellow viscous solution. It is supplied as a 
nonaqueous solution intended for dilution prior to IV infusion. 
9.1.5. 
Pemetrexed 
Pemetrexed will be supplied as a single vial (Pemetrexed [pemetrexed disodium] 500 mg/vial, 
lyophilized powder for infusion). 
9.1.6. 
Nab-Paclitaxel 
Nab-paclitaxel will be supplied as a single vial of lyophilized powder containing 100 mg of 
paclitaxel in a single-use vial for reconstitution. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy 
Clinical Study Protocol Study 3000-01-002 Version 3.0 
Confidential 
Page 125 of 259 
9.1.7. 
Bevacizumab 
Bevacizumab (Avastin) is a clear to slightly opalescent, colorless to pale brown, sterile, pH 6.2 
solution for IV infusion.110 The excipients for bevacizumab are trehalose dihydrate, sodium 
phosphate, polysorbate 20, and water for injections. Bevacizumab is obtained from commercial 
sources according to local practice standards and it is provided as a commercially available 
dosage. 
9.2. 
Administration 
9.2.1. 
Niraparib 
Niraparib will be supplied as 100-mg capsules and will be administered orally QD continuously 
at the assigned dose (see Table 48 for Part A and Table 50 for Part C). On Day 1 of each cycle, a 
niraparib dose will be administered upon completion of all infusions. Depending on the dose 
regimen, 2 or 3 capsules of 100-mg strength niraparib will be taken at each dose administration 
(total dose of 200 or 300 mg per dose regimen, respectively). Subsequent to Amendment 1, only 
patients with a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 μL 
will be eligible to receive niraparib 300 mg as a stating dose. Patients will be instructed to take 
their niraparib dose at the same time each day; bedtime administration may be a potential method 
for managing nausea. Patients must swallow and not chew all capsules. The consumption of 
water and food is permissible. 
Niraparib will be dispensed to patients on Day 1 of every 21-day cycle for up to 2 years or until 
disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
Continued treatment with niraparib beyond 2 years may be considered following discussion 
between the Sponsor and Investigator. 
The Pharmacy Manual contains descriptions of the packaging of niraparib and instructions for 
the preparation and administration of niraparib. 
9.2.2. 
TSR-042 
TSR-042 will be administered at the study site by a 30-minute IV infusion on Day 1 of every 
21-day cycle (Q3W) at 500 mg for the first 4 cycles. Beginning on Day 1 of Cycle 5, TSR-042 
will be administered at 1,000 mg on Day 1 of every other cycle (Q6W) to patients in Parts A, B, 
C, and D for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, 
Investigator’s decision, or death. Patients in Parts E, F, G, H, and I will continue to receive 500 
mg on Day 1 of every cycle (Q3W) throughout the study. Continued treatment with TSR-042 
beyond 2 years may be considered following discussion between the Sponsor and Investigator. 
The Pharmacy Manual contains descriptions of the packaging of TSR-042 and instructions for 
the preparation and administration of TSR-042.  (See Table 48 for Part A, Table 49 for Part B, 
Table 50 for Part C, Table 51 for Part D, Table 52 for Part E, Table 53 for Part F, Table 54 for 
Part G, Table 55 for Part H, and Table 56 for Part I.) 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 126 of 259 
 
9.2.3. 
TSR-022 
TSR-022 will be administered at the study site by a 30-minute IV infusion on Day 1 of every 
21-day Cycle (Q3W) at 900 mg (or 300 mg if lowered to dose level -1 for reasons of safety) for 
up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, 
Investigator’s decision, or death. All patients should be monitored on site for AEs for at least 
4 hours after the completion of infusion for the first and second doses. Continued treatment with 
TSR-022 beyond 2 years may be considered following discussion between the Sponsor and 
Investigator.  
The Pharmacy Manual contains descriptions of the packaging of TSR-022 and instructions for 
the preparation and administration of TSR-022. 
9.2.4. 
Carboplatin-Paclitaxel 
Paclitaxel will be administered at the study site by a 3-hour IV infusion on Day 1 of every 
21-day cycle (Q3W) at 175 mg/m2 for 4 to 6 cycles or until disease progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death. The paclitaxel package insert 
contains descriptions of the packaging of paclitaxel and instructions for preparation and 
administration of paclitaxel.  
Carboplatin will be administered at the study site by a 30- or 60-minute IV infusion (30 minutes 
preferred) on Day 1 of every 21-day cycle (Q3W) at an area under the plasma or serum 
concentration-time curve (AUC) of 5 or 6, and will be administered for 4 to 6 cycles as clinically 
indicated. The carboplatin dose will be determined by the Investigator, taking into consideration 
the patient’s prior anticancer therapies and pre-existing medical conditions. The carboplatin 
package insert contains descriptions of the packaging of carboplatin and instructions for 
preparation and administration of carboplatin.  
The order of administration of both agents is as follows: TSR-042 (followed by TSR-022 in 
Part I only) followed by paclitaxel (see Table 49 for Part B, Table 51 for Part D, and Table 56 for 
Part I). 
9.2.5. 
Carboplatin-Pemetrexed 
Pemetrexed will be administered at the study site by a 10-minute IV infusion on Day 1 of every 
21-day cycle (Q3W) at 500 mg/m2 for up to 2 years or until progression, unacceptable toxicity, 
patient withdrawal, Investigator’s decision, or death. The pemetrexed package insert contains 
descriptions of the packaging of pemetrexed and instructions for preparation and administration 
of pemetrexed. Continued treatment with pemetrexed beyond 2 years may be considered 
following discussion between the Sponsor and Investigator. 
All patients should receive the appropriate supplementation of vitamin B12 and folic acid as 
listed below: 
 Folic acid 350 to 1,000 μg oral: At least 5 doses of folic acid must be taken during the 
7 days preceding the first dose of pemetrexed, and folic acid dosing must continue 
during the full course of therapy and for 21 days after the last dose of pemetrexed. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 127 of 259 
 
 Vitamin B12 1,000 μg intramuscular injection will be administered in the week 
preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent 
vitamin B12 injections may be given the same day as pemetrexed administration. 
Carboplatin will be administered at the study site by a 30- or 60-minute IV infusion (30 minutes 
preferred) on Day 1 of every 21-day cycle (Q3W) at an area under the plasma or serum 
concentration-time curve (AUC) of 5 or 6, and will be administered for 4 to 6 cycles as clinically 
indicated. The carboplatin dose will be determined by the Investigator, taking into consideration 
the patient’s prior anticancer therapies and pre-existing medical conditions. The carboplatin 
package insert contains descriptions of the packaging of carboplatin and instructions for 
preparation and administration of carboplatin. 
Both agents will be administered at the study site on Day 1 of every 21-day cycle (Q3W) after 
administration of TSR-042 and will be administered for 4 to 6 cycles as clinically indicated, and 
thereafter pemetrexed will be administered for up to 2 years or until progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death. (Order of administration: TSR-042 
infusion [followed by TSR-022 in Part F only] followed by pemetrexed infusion followed by 
carboplatin infusion.) (See Table 52 for Part E and Table 53 for Part F.) 
9.2.6. 
Carboplatin–Nab-Paclitaxel 
Nab-paclitaxel will be administered at the study site by a 30-minute IV infusion on Days 1, 8, 
and 15 (Q1W) of every 21-day cycle at 100 mg/m2 for 4 to 6 cycles as clinically indicated or 
until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or 
death, after administration of TSR-042 for Part G (see Table 54) and after administration of 
TSR-042 and TSR-022 for Part H (see Table 55).  
The nab-paclitaxel package insert contains descriptions of the packaging of nab-paclitaxel and 
instructions for preparation and administration of nab-paclitaxel. 
Carboplatin will be administered at the study site by a 30- or 60-minute IV infusion (30 minutes 
preferred) on Day 1 of every 21-day cycle (Q3W) an area under the plasma or serum 
concentration-time curve (AUC) of 5 or 6, and will be administered for 4 to 6 cycles as clinically 
indicated, after administration of TSR-042 and nab-paclitaxel for Part G (see Table 54) and after 
administration of TSR-042, TSR-022, and nab-paclitaxel for Part H (see Table 55). The 
carboplatin dose will be determined by the Investigator, taking into consideration the patient’s 
prior anticancer therapies and pre-existing medical conditions. 
The carboplatin package insert contains descriptions of the packaging of carboplatin and 
instructions for preparation and administration of carboplatin. 
9.2.7. 
Bevacizumab 
Bevacizumab will be administered at the study site by IV infusion based on local approved 
product label 111 on Day 1 of every 21-day cycle (Q3W) at 15 mg/kg for up to 15 months or until 
progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
This agent will be administered after administration of TSR-042 in Part C and after 
administration of TSR-042, paclitaxel, and carboplatin in Part D (See Table 50 for Part C and 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 128 of 259 
 
Table 51 for Part D).The bevacizumab package insert contains descriptions of the packaging of 
bevacizumab and instructions for the preparation and administration of bevacizumab. 
9.2.8. 
Order of Administration 
The order of study drug administration for each part is listed below: 
 Part A: TSR-042 followed by niraparib after completion of infusion 
 Part B: TSR-042 followed by paclitaxel, then carboplatin 
 Part C: TSR-042 followed by bevacizumab, then niraparib after completion of both 
infusions 
 Part D: TSR-042 followed by paclitaxel, then carboplatin then bevacizumab 
 Part E: TSR-042 followed by pemetrexed, then carboplatin  
 Part F: TSR-042 followed by TSR-022, then pemetrexed, then carboplatin 
 Part G: TSR-042 followed by nab-paclitaxel, then carboplatin 
 Part H: TSR-042 followed by TSR-022, then nab-paclitaxel, then carboplatin 
 Part I: TSR-042 followed by TSR-022, then paclitaxel, then carboplatin 
9.3. 
Dose Modification 
Dose modification of study treatment will be conducted as described in Section 6.4.1. 
9.4. 
Study Drug Packaging, Labeling, and Storage 
The label text of the study treatments will comply with Good Manufacturing Practice and 
national legislation to meet the requirements of the participating countries. The study treatment 
will be open-label and non-patient-specific. 
All study treatment supplies must be stored in accordance with the Pharmacy Manual 
instructions and package labeling. Until dispensed or administered to the patients, the study 
treatment will be stored in a securely locked area that is accessible to authorized personnel only. 
9.5. 
Study Drug Accountability 
The Investigator or designee is responsible for maintaining accurate dispensing records of the 
study treatments throughout the clinical study. Study drug accountability for niraparib should be 
maintained by the study site based on the number of capsules dispensed versus the number of 
capsules returned to the study site at each visit and the number of days since the last visit. 
Details of maintaining drug accountability, including information on the accountability log, will 
be provided in the Pharmacy Manual.  
All dispensation and accountability records will be available for Sponsor review. The study 
monitor will assume the responsibility to reconcile the study treatment accountability log. The 
pharmacist will dispense study treatment for each patient according to the protocol and 
Pharmacy Manual, if applicable. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 129 of 259 
 
9.6. 
Study Drug Handling and Disposal 
At the end of study, when all patients have stopped protocol treatment, complete drug 
reconciliation per batch should be available at the site for verification in order to allow drug 
destruction or return procedure. All dispensing and accountability records will be available for 
Sponsor review. After receiving Sponsor approval in writing, the investigational site is 
responsible for destruction of study treatment according to local regulations. If a site does not 
have the capability for on-site destruction, the Sponsor will provide a return for destruction 
service to a third party.  
Both the unused and expired study treatment must be destroyed, upon authorization of the 
Sponsor, according to local regulations and procedures, and a copy of the destruction form must 
be filed in the study binder. 
The study treatment provided for this study is to be used only as indicated in this protocol and 
only for the patients entered in this study. 
9.7. 
Previous and Concomitant Medications 
9.7.1. 
Recording of Previous and Concomitant Medications 
Any medication the patient takes during the study other than the study treatments, including 
herbal and other nontraditional remedies, is considered a concomitant medication. All 
concomitant medications must be recorded in the eCRF. The following information must be 
recorded in the eCRF for each concomitant medication: generic name, route of administration, 
start date, stop date, dosage, and indication. Any changes in the dosage or regimen of a 
concomitant medication must be recorded in the eCRF. 
At screening, patients will be asked what medications they have taken during the last 30 days. At 
each subsequent study visit, patients will be asked what concomitant medications they are 
currently taking or have taken since the previous visit. 
The niraparib and carboplatin safety profiles includes risk for thrombocytopenia; therefore, 
investigators should be advised to use caution with anticoagulation and antiplatelet drugs. 
The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. Investigators are advised to 
use caution when administering paclitaxel concomitantly with known substrates, inducers or 
inhibitors of CYP2C8 and CYP3A4 (see Table 57 in Appendix A). 
9.7.2. 
Prohibited Medications 
Known prior medications that exclude a patient from participating in the study are described in 
the exclusion criteria (see Section 7.2). 
Patients in all parts are prohibited from receiving the following therapies during the screening 
and treatment phase of this study: 
 Systemic anticancer or biological therapy. For patients with castration resistant 
prostate cancer, it is allowed to continue androgen deprivation therapy after cycle 1. 
 Immunotherapy not specified in this protocol. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 130 of 259 
 
 Chemotherapy not specified in this protocol. 
 Investigational agents other than niraparib, TSR-042, TSR-022, carboplatin-
paclitaxel, bevacizumab, pemetrexed, and nab-paclitaxel. 
 Radiation therapy is prohibited within 3 weeks prior to Day 1 and during study 
treatment. Note: Palliative radiation therapy to a small field >1 week prior to Day 1 of 
study treatment may be allowed. Palliative radiation therapy to a small field is 
allowed after Cycle 1 after consultation with the Sponsor. 
 Any surgery that involves tumor lesions, except for diagnostic biopsy.  
 Systemic glucocorticoids for any purpose other than to manage symptoms of 
suspected irAEIs. (Note: Use of inhaled steroids, local injection of steroids, topical 
steroids, and steroid eye drops are allowed). If medically deemed necessary (e.g., 
acute asthma or chronic obstructive pulmonary disease exacerbation), Investigators 
are allowed to use their judgment to treat patients with systemic steroids. In such 
cases, systemic steroids should be stopped at least 24 hours prior to the next dose of 
TSR-042 and/or TSR-022. 
 Live vaccines within 14 days prior to the first dose of study treatment. Seasonal flu 
vaccines that do not contain live viruses are allowed. Examples of live vaccines 
include, but are not limited to, the following: measles, mumps, rubella, chicken pox, 
yellow fever, rabies, bacille Calmette-Guerin, and typhoid (oral) vaccine. Seasonal 
influenza vaccines for injection are generally killed virus vaccines and are allowed. 
Intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not 
allowed. 
 Prophylactic cytokines (i.e., granulocyte colony-stimulating factor [GCSF]) should 
not be administered in the first cycle of the study but may be administered in 
subsequent cycles according to current American Society of Clinical Oncology 
(ASCO) guidelines.112  
In addition, niraparib has been shown to weakly induce cytochrome P450 (CYP) 1A2 in vitro 
and is an insensitive substrate for P-glycoprotein (P-gp). Therefore, investigators and patients 
should be advised to use caution with drugs that are sensitive substrates of CYP1A2 with narrow 
therapeutic range, such as theophylline and tizanidine. The niraparib safety profile includes risk 
for thrombocytopenia, and bevacizumab may increase the potential for bleeding (hemorrhage); 
therefore, patients should be advised to use caution with anticoagulants (e.g., warfarin) and 
antiplatelet drugs (e.g., aspirin).  
Physicians should follow the current versions of the niraparib Investigator’s Brochure, the 
Zejula® package insert113, the Avastin® [Genentech/Roche US] package insert111, the TSR-042 
Investigator’s Brochure, the carboplatin package insert114, the paclitaxel package insert115, the 
pemetrexed package insert116, and the nab-paclitaxel package insert74 for information on the 
general management of the patients receiving these therapies. 
Patients in Parts B, D, E, F, G, H, and I are additionally prohibited from receiving the following 
therapies during the screening and treatment phase of this study: 
 Aminoglycocides  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 131 of 259 
 
 Known ototoxic agents 
9.7.3. 
Contraception 
TSR-042, TSR-022, and niraparib are known to have properties that require the patient to use 
contraception. For details on niraparib, refer to the Investigator’s Brochure.  
It is not known if TSR-042 or TSR-022 may have adverse effects on a fetus in utero. However, 
blockade of PD-L1 and TIM-3 signaling in murine models of allogeneic pregnancy can eliminate 
fetomaternal tolerance and cause spontaneous abortion as indicated by increase in embryo 
resorption and a reduction in litter size and TIM-3 down-regulation has been correlated with 
human miscarriage.117-119 Therefore, female patients of childbearing potential may only be 
enrolled if they have a negative serum pregnancy test within 72 hours prior to taking study 
treatment. Female patients must agree to abstain from activities that could result in pregnancy 
from screening through 180 days after the last dose of study treatment, be willing to use 2 
adequate barrier methods or a barrier method plus a hormonal method throughout the study, or 
be of nonchildbearing potential, as defined in Section 7.1.  
Male patients are required to use an adequate method of contraception starting with the first dose 
of study treatment through 90 days after the last dose of study treatment. 
The following are considered highly effective methods of contraception: combined (estrogen and 
progesterone containing) hormonal contraception associated with inhibition of ovulation 
(including oral, intravaginal, or transdermal agents); progesterone-only hormonal contraception 
associated with inhibition of ovulation (including oral, injectable, or implantable agents); 
intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal 
occlusion; vasectomized partner; or sexual abstinence. 
Patients should be informed that taking the study treatment may involve unknown risks to the 
fetus (unborn baby) if pregnancy were to occur during the study. To participate in the study they 
must adhere to the contraception requirement (described above) for the duration of the study and 
through 180 days after the last study treatment. If there is any question that a patient will not 
reliably comply with the requirements for contraception, that patient should not be enrolled into 
the study. 
9.7.4. 
Rescue Medications and Supportive Care Guidelines 
Supportive care measures for AEs during treatment with niraparib, carboplatin, paclitaxel, 
bevacizumab, pemetrexed, and nab-paclitaxel should be provided as deemed necessary by the 
treating Investigator according to local institutional practice and/or guidance in the appropriate 
prescribing information. 
During treatment with TSR-042 and/or TSR-022, patients should receive appropriate supportive 
care measures for AEs as deemed necessary by the treating Investigator, including but not 
limited to the items outlined below. Prophylactic cytokines (e.g., GCSF) should be administered 
according to current ASCO guidelines.112 Note: It may be necessary to perform additional 
procedures such as bronchoscopy, endoscopy, or skin photography as part of the evaluation of 
the AE. The following sections detail specific guidance by type of AE. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 132 of 259 
 
9.7.4.1. 
Pneumonitis 
 Treat with systemic corticosteroids, oral for Grade 2 (e.g., 0.5 to 1 mg/kg/day of 
prednisone or equivalent) and IV for Grade 3 or 4 (e.g., 1 to 2 mg/kg/day of 
prednisone or equivalent). 
 Administer additional anti-inflammatory measures, as needed. 
 Taper corticosteroids when symptoms improve to Grade 1 or less over no less than 
4 weeks. 
 If Grade 2 and no improvement or worsening over 2 weeks, treat as Grade 3 or 4. 
 Consider prophylactic antibiotics for opportunistic infections in the case of prolonged 
steroid administration. 
9.7.4.2. 
Diarrhea/Colitis 
 Monitor carefully for signs and symptoms of enterocolitis (such as diarrhea, 
abdominal pain, blood or mucus in stool, with or without fever) and of bowel 
perforation (such as peritoneal signs and ileus). 
 All patients who experience diarrhea/colitis should be advised to drink liberal 
quantities of clear fluids. If sufficient oral fluid intake is not feasible, fluid and 
electrolytes should be substituted via IV infusion. 
 For Grade 2 diarrhea/colitis that persists >3 days, administer oral corticosteroids 
(e.g., 0.5 to 1.0 mg/kg/day of prednisone or equivalent). If symptoms persist or 
worsen with steroids, treat as Grade 3 or 4. 
 For Grade 3 or 4 diarrhea/colitis that persists >3 days, treat with IV steroids 
(e.g., 1 to 2 mg/kg/day of prednisone or equivalent) followed by high-dose oral 
steroids. 
 Taper corticosteroids when symptoms improve to Grade 1 or less over no less than 
4 weeks. 
9.7.4.3. 
Type 1 Diabetes Mellitus or Grade 3 or 4 Hyperglycemia 
For type 1 diabetes mellitus and for Grade 3 or 4 hyperglycemia associated with metabolic 
acidosis or ketonuria, insulin replacement therapy is required. 
9.7.4.4. 
Hypophysitis 
 Treat with systemic corticosteroids, oral for Grade 2 (e.g., 0.5 to 1 mg/kg/day of 
prednisone or equivalent) and IV for Grade 3 or 4 (e.g., 1 to 2 mg/kg/day of 
prednisone or equivalent). 
 Taper corticosteroids when symptoms improve to Grade 1 or less over no less than 
4 weeks. 
 Replacement of appropriate hormones may be required as the steroid dose is tapered. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 133 of 259 
 
9.7.4.5. 
Hyperthyroidism or Hypothyroidism 
Thyroid disorders have been reported with other PD-1 inhibitors occurring at any time during 
treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically 
during treatment, and as indicated based on clinical evaluation) and for clinical signs and 
symptoms of thyroid disorders. 
 Grade 2 HYPERthyroidism: Consider non-selective beta-blockers (e.g., propranolol) 
as initial therapy. 
 Grade 3 or 4 HYPERthyroidism: Treat with an initial dose of IV corticosteroids 
followed by oral corticosteroids (e.g., 0.5 to 1 mg/kg/day of prednisone or 
equivalent). Taper corticosteroids when symptoms improve to Grade 1 or less over no 
less than 4 weeks. Replacement of appropriate hormones may be required as the 
steroid dose is tapered. 
 Grade 2 to 4 HYPOthyroidism: Thyroid hormone replacement therapy, with 
levothyroxine or liothyronine, is indicated per standard of care. 
9.7.4.6. 
Hepatitis 
 Treat with systemic corticosteroids, oral for Grade 2 (initial dose of 1 to 2 mg/kg/day 
of prednisone or equivalent) and IV for Grade 3 or 4 (1 to 2 mg/kg/day of prednisone 
or equivalent).  
 Taper corticosteroids when symptoms improve to Grade 1 or less over no less than 
4 weeks. 
9.7.4.7. 
Renal Failure or Nephritis 
 Treat with systemic corticosteroids, oral for Grade 2 (initial dose of 0.5 to 
1 mg/kg/day of prednisone or equivalent) and IV for Grade 3 or 4 (1 to 2 mg/kg/day 
of prednisone or equivalent). 
 Taper corticosteroids when symptoms improve to Grade 1 or less over no less than 
4 weeks. 
9.7.4.8. 
Management of Infusion-Related Reactions  
Signs and symptoms usually develop during or shortly after drug infusion and generally resolve 
completely within 24 hours of completion of infusion. Table 16 shows treatment guidelines for 
patients who experience an infusion-related reaction associated with administration of TSR-042 
and/or TSR-022. 
Table 16: 
TSR-042 and TSR-022 Infusion Reaction Treatment Guidelines 
CTCAE Grade 
Treatment 
Premedication at Subsequent 
Dosing 
Grade 1 
Mild reaction; infusion 
interruption not indicated; 
intervention not indicated  
Increase monitoring of vital signs as 
medically indicated until the patient is 
deemed medically stable in the opinion of 
the Investigator. 
None. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 134 of 259 
 
CTCAE Grade 
Treatment 
Premedication at Subsequent 
Dosing 
Grade 2 
Requires infusion interruption 
but responds promptly to 
symptomatic treatment 
(e.g., antihistamines, NSAIDs, 
narcotics, or IV fluids); 
prophylactic medications 
indicated for ≤24 h 
Stop infusion and monitor symptoms. 
Additional appropriate medical therapy 
may include but is not limited to:  
 
IV fluids 
 
Antihistamines 
 
NSAIDs 
 
Acetaminophen 
 
Narcotics 
Increase monitoring of vital signs as 
medically indicated until the patient is 
deemed medically stable in the opinion of 
the Investigator. 
If symptoms resolve within 1 hour of 
stopping drug infusion, the infusion may 
be restarted at 50% of the original 
infusion rate (e.g., from 100 mL/h to 50 
mL/h). Otherwise, dosing will be 
withheld until symptoms resolve, and the 
patient should be premedicated for the 
next scheduled dose. 
Patients who develop Grade 2 toxicity 
despite adequate premedication should be 
permanently discontinued from further 
study treatment administration. 
Patient may be premedicated 1.5 h 
(±30 min) prior to infusion of 
TSR-042 and/or TSR-022 with:  
 
Diphenhydramine 
50 mg PO (or 
equivalent dose of 
antihistamine) 
 
Acetaminophen 500 
to 1,000 mg PO (or 
equivalent dose of 
antipyretic) 
Grade 3: 
Prolonged (i.e., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial improvement; 
hospitalization indicated for 
other clinical sequelae (e.g., 
renal impairment, pulmonary 
infiltrates) 
Grade 4: 
Life-threatening; pressor or 
ventilatory support indicated  
Stop Infusion. 
Additional appropriate medical therapy 
may include but is not limited to:  
 
IV fluids 
 
Antihistamines 
 
NSAIDs 
 
Acetaminophen 
 
Narcotics 
 
Oxygen 
 
Pressors 
 
Corticosteroids 
 
Epinephrine 
Increase monitoring of vital signs as 
medically indicated until the patient is 
No subsequent dosing. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 135 of 259 
 
CTCAE Grade 
Treatment 
Premedication at Subsequent 
Dosing 
deemed medically stable in the opinion of 
the Investigator. 
Hospitalization may be indicated. 
Patient is permanently discontinued 
from further study treatment 
administration. 
Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events; IV = intravenous; NSAID = 
nonsteroidal anti-inflammatory drug; PO = oral. 
Note: Appropriate resuscitation equipment should be available in the room and a physician readily available during 
the period of study treatment administration. 
9.7.5. 
Other Study Restrictions 
Patients who are blood donors should not donate blood during the study and for 90 days after the 
last dose of study treatment. 
Patients should maintain a normal diet unless modifications are required to manage an AE such 
as diarrhea, nausea, or vomiting. 
For Parts E and F, use caution in patients with mild to moderate renal insufficiency (creatinine 
clearance of 45 to 79 mL/min). Caution should be used when administering ibuprofen 
concurrently with pemetrexed to patients with mild to moderate renal insufficiency (creatinine 
clearance from 45 to 79 mL/min). Other NSAIDs should also be used with caution. 
9.8. 
Treatment Compliance 
Compliance with inclusion and exclusion criteria will be assessed as outlined in Section 7.1 and 
Section 7.2. 
Carboplatin-paclitaxel, carboplatin-pemetrexed, carboplatin–nab-paclitaxel, TSR-042, TSR-022, 
and bevacizumab will be administered by site personnel at study sites as detailed in Section 9.2.  
Study drug accountability will be monitored as detailed in Section 9.5. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 136 of 259 
 
10. 
ENDPOINTS AND METHODS OF ASSESSMENT 
10.1. 
Efficacy Endpoints 
10.1.1. 
Evaluation of Tumor Response 
10.1.1.1. Overview 
The efficacy of TSR-042 with niraparib combination treatment (Part A), TSR-042 with niraparib 
and bevacizumab combination treatment (Part C), TSR-042 and carboplatin-paclitaxel 
combination treatment (Part B), TSR-042 with carboplatin-paclitaxel and bevacizumab 
combination treatment (Part D), TSR-042 with carboplatin-pemetrexed combination treatment 
(Part E), and TSR-042 with TSR-022 and carboplatin-pemetrexed combination treatment 
(Part F), TSR-042 with carboplatin–nab-paclitaxel combination treatment (Part G), TSR-042 
with TSR-022 and carboplatin–nab-paclitaxel combination treatment (Part H), and TSR-042 with 
TSR-022 and carboplatin-paclitaxel combination treatment (Part I) will be evaluated by 
assessment of tumor response to treatment according to RECIST v1.1120 per Investigator 
assessment. Serum tumor marker data will not be used for defining objective responses or 
disease progression; however, serum tumor marker data can be used for clinical decisions. 
Response to treatment will be based on Investigator evaluation of radiographic images.  
Tumor imaging (chest, abdomen, and pelvis [plus head if clinically indicated]) should be 
performed by CT (preferred). MRI should only be used when CT is contraindicated or for 
imaging of the head, but the same imaging technique should be used in a patient throughout the 
study. CT scan is the more commonly used modality and is preferred for the majority of patients. 
An MRI can be utilized if clinically appropriate. Positron emission tomography (PET)/CT may 
be used according to RECIST v1.1 guidelines. If the chest and/or head CT/MRI is clear at 
screening, repeat imaging of these areas is not required in the absence of clinical indication 
requiring follow‐up. Bone scans should be conducted per standard of care. 
10.1.1.2. Timing of Radiographic Evaluations 
All patients will undergo serial radiographic assessments to assess tumor response. Initial tumor 
imaging at screening must be performed within 21 days prior to the date of the first dose of study 
treatment. Scans performed prior to the signing of the ICF as part of routine clinical management 
are acceptable for use as initial tumor imaging if they are of diagnostic quality and performed 
within 21 days prior to first dose date. 
The first on-study imaging assessment will be performed at 12 weeks (84 ± 10 days) from the 
date of the first dose of study treatment. Subsequent tumor imaging should be performed every 
12 weeks (84 ± 10 days) thereafter until progression while on study treatment, independent of 
cycle delays or dose interruptions, or at any time when progression of disease is suspected. 
CT or MRI of the head will be conducted if clinically indicated; bone scans will be conducted 
per standard of care. Imaging should not be delayed for delays in cycle starts or extension of 
combination treatment cycle intervals. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 137 of 259 
 
Per RECIST v1.1 (see Appendix B), CR or PR should be confirmed, and tumor imaging for 
confirmation of response may be performed at the earliest 4 weeks after the first indication of 
response or at the next scheduled scan (i.e., 12 weeks later), whichever is clinically indicated. 
Imaging should be continued until whichever of the following occurs: 
 The start of new anticancer treatment 
 Withdrawal of consent 
 Lost to follow-up  
 Death 
 End of the study (when responder or discontinuation status for all patients is known) 
There is accumulating evidence indicating clinical benefit in a subset of patients treated with 
immunotherapy despite initial evidence of progressive disease (PD).121 Therefore, patients with 
initial radiologic evidence of PD who are clinically stable may continue study treatment at the 
Investigator’s discretion while awaiting confirmatory tumor imaging. Confirmatory imaging of 
PD must be performed after initial evidence of PD. Patients with confirmed PD may continue 
study treatment at the Investigator’s discretion until the Investigator has determined that the 
patient is no longer experiencing clinical benefit or until study treatment is no longer tolerated by 
the patient. 
Patients who discontinue study treatment for reasons other than PD will continue post-treatment 
imaging studies for disease status follow-up at the same frequency as already followed (e.g., 
every 12 weeks [84 ± 10 days]) until disease progression, start of a non–study anticancer 
treatment, withdrawal of consent to study participation, becoming lost to follow-up, death, or end 
of the study. 
10.1.1.3. Assessment of Response by RECIST v1.1 
RECIST v1.1 will be used by the Investigator as the primary measure for assessment of tumor 
response, date of disease progression, and as a basis for all protocol guidelines related to disease 
status.  
Details on RECIST v1.1, including evaluation of target and non-target lesions and definitions of 
response are provided in Appendix B. 
10.1.2. 
Secondary Endpoints 
10.1.2.1. Objective Response Rate 
ORR will be evaluated as a secondary endpoint and is defined as the proportion of patients who 
have achieved confirmed CR or PR, evaluated using RECIST v1.1 (Appendix B) based on 
Investigator assessment. Tumor assessments after the initiation of further anticancer therapy are 
excluded for the assessment of best overall response. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 138 of 259 
 
10.1.2.2. Duration of Response 
DOR will be evaluated as a secondary endpoint and is defined as the time from first 
documentation of response (CR or PR) until the time of first documentation of disease 
progression by RECIST v1.1 (Appendix B) or death by any cause.  
10.1.2.3. Disease Control Rate 
DCR will be assessed as a secondary endpoint and is defined as the percentage of patients who 
have achieved CR, PR, or stable disease (SD) per RECIST v1.1 (Appendix B). 
10.1.2.4. Progression-Free Survival 
PFS will be assessed as a secondary endpoint and is defined as the time from the date of the first 
dose of study treatment to the earlier date of assessment of progression, or death by any cause in 
the absence of progression by RECIST v1.1 (Appendix B).  
10.2. 
Pharmacokinetic Assessments 
Plasma and serum samples for PK determination will be collected from all patients enrolled in all 
parts of the study. All sampling times are relative to the start dose of the corresponding agent. 
For Part A (TSR-042 and niraparib combination treatment) and Part C (TSR-042, niraparib, and 
bevacizumab combination treatment), plasma will be analyzed using liquid chromatography with 
mass spectrometry detection for niraparib and its major metabolite M1. The serum will be 
analyzed for TSR-042 using enzyme-linked immunosorbent assay (ELISA).  
For Part B (TSR-042 and carboplatin-paclitaxel combination treatment), Part D (TSR-042, 
carboplatin-paclitaxel, and bevacizumab combination treatment), Part E (TSR-042 and 
carboplatin-pemetrexed combination treatment), Part F (TSR-042, TSR-022, and 
carboplatin-pemetrexed combination treatment), Part G (TSR-042 and carboplatin–
nab-paclitaxel combination treatment), Part H (TSR-042, TSR-022, and carboplatin–
nab-paclitaxel), and Part I (TSR-042, TSR-022, and carboplatin-paclitaxel), serum samples will 
be analyzed for TSR-042 and TSR-022 using ELISA. The plasma samples will be analyzed for 
carboplatin using inductively coupled plasma mass spectrometry, and for paclitaxel, pemetrexed, 
and nab-paclitaxel using liquid chromatography tandem-mass spectrometry, if appropriate. 
10.3. 
Immunogenicity Assessments 
Serum samples for the determination of TSR-042 and TSR-022 ADAs will be the same samples 
collected for TSR-042 and TSR-022 PK assessments. ADAs will be analyzed in a tiered 
approach using electrochemiluminescence (i.e., screening, confirmation, titer, and neutralizing 
antibody assay). Minimally, ADAs will be analyzed in predose samples from all cycles 
collected; additional samples for ADA determination will be collected upon treatment 
discontinuation at a safety follow-up visit (i.e., approximately 90 days after the last dose of TSR-
042 and TSR-022). 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 139 of 259 
 
10.4. 
Biomarker Assessments 
FFPE tumor archival tissue samples (mandatory [if available] for Parts F, H, and I; optional for 
Parts A, B, C, D, E, and G) and blood samples will be assessed for biomarkers that may correlate 
with clinical benefit from TSR-042 and niraparib combination treatment (Part A); TSR-042 and 
carboplatin-paclitaxel combination treatment (Part B); TSR-042, niraparib, and bevacizumab 
combination treatment (Part C); TSR-042, carboplatin-paclitaxel, and bevacizumab combination 
treatment (Part D); TSR-042 and carboplatin-pemetrexed combination treatment (Part E); TSR-
042, TSR-022, and carboplatin-pemetrexed combination treatment (Part F); TSR-042 and 
carboplatin–nab-paclitaxel combination treatment (Part G); TSR-042, TSR-022, and carboplatin–
nab-paclitaxel combination treatment (Part H); and TSR-042, TSR-022, and carboplatin-
paclitaxel combination treatment (Part I), including, but not limited to, gBRCAmut, HRD status, 
the phenotype and molecular profile of immune cells, expression of PD-L1 on tumor cells, and 
cytokines or chemokines prior to and during treatment. To enable these evaluations, blood 
samples for biomarker analysis will be obtained in Parts A, B, C, and D at the time of screening, 
at predose on Day 1 of Cycles 1 and 2, and at EOT or time of disease progression. Blood 
samples for biomarker analysis will be obtained in Parts E, F, G, H, and I at the screening visit, 
predose on Days 1 and 15 of Cycle 1 and predose on Day 1 of Cycles 2, 4, and 6, and at EOT or 
time of disease progression. 
Biopsies are an integral component of this study to enable an assessment of the 
pharmacodynamic effects of TSR-042 in combination with niraparib, carboplatin-paclitaxel, 
bevacizumab, carboplatin-pemetrexed, and TSR-022, as well as to develop an understanding of 
the tumor micro-environment, including but not limited to immune cells, tumor characteristics, 
and immune-related gene and protein expression and how they relate to clinical response. 
On-treatment and progression (EOT visit) biopsies are optional for patients in Parts E, F, G, H, 
and I. In the subset of patients who undergo serial biopsies, biomarkers will be evaluated in new 
tumor samples obtained at approximately 4 to 6 weeks after initiating study treatment and at time 
of disease progression (EOT visit). Evaluation of these tumor tissue samples may include but not 
be limited to analyses of immune cells, gene-expression profiling for immune-related and tumor-
related proteins, and assessment of tumor genome for mutations and/or alterations. In addition to 
monitoring of the immune response, tumor cell characteristics may be correlated with other 
immune-related biomarkers and with clinical activity. Therefore, all patients should be 
considered for research tumor tissue biopsies, if it is deemed safe and clinically appropriate. 
During screening, the Investigator will assess the feasibility of obtaining tumor tissue biopsies 
from each patient. Typically, this will require that the tumor lesions be superficially accessible, 
as occurs with some subcutaneous and lymph node metastases, or that the lesions can be safely 
biopsied under CT scan or ultrasound guidance. It is preferred that for tumor biopsies that are not 
simply incisional or excisional, a 16-gauge core biopsy needle is used; however, a smaller bore 
needle may be used if considered necessary for the patient’s safety. Several core biopsies with 
the same smaller (than 16 gauge) needle need to be obtained. Fine needle biopsies are not 
recommended for this study. Pleural effusions or lung aspirate samples cannot be substituted for 
tumor biopsies. Patients undergoing tumor biopsy must have PT/aPTT  1.5 × ULN. Details on 
sample collection and management are provided in the Study Laboratory Manual. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 140 of 259 
 
10.5. 
Use of Remaining Study Patient Specimens/Samples 
Following the conclusion of the study, patient samples that have not been depleted may be stored 
and used for future additional research. This research will help understand disease subtypes, drug 
response, and toxicity, and possibly to identify new biomarkers that predict subject response to 
treatment. This use of the samples for internal research will be done in accordance with the 
guidelines defined by the FDA document “Guidance on Informed Consent for In Vitro 
Diagnostic Device Studies Using Leftover Human Specimens that are Not Individual 
Identifiable”122 and European Medicines Agency’s (EMEA’s) Reflection Paper on 
Pharmacogenetic Samples, Testing, and Data Handling.123 If a patient requests destruction of 
their tissue and blood samples and the samples have not yet been de-identified, the sponsor (or 
central laboratory) will destroy the samples as described in this FDA guidance. The sponsor (or 
central laboratory) will notify the investigator in writing that the samples have been destroyed. 
10.6. 
Safety Endpoints 
Safety parameters evaluated during the conduct of the study include TEAEs, clinical laboratory 
values (hematology, serum chemistry, coagulation, thyroid function, and urinalysis), vital signs, 
ECGs, physical examination findings, and use of concomitant medications.  
All safety parameters will be performed in accordance with the schedules of events 
(Section 11.1). 
10.6.1. 
Definitions 
10.6.1.1. Adverse Event (AE) 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
medicinal product and which does not necessarily have to have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including a clinically 
significant abnormal laboratory finding, for example), symptom, or disease temporally 
associated with the use of study treatment, whether or not considered related to the study 
treatment.  
AEs may include the onset of new illness and the exacerbation of pre-existing medical 
conditions. An AE can include an undesirable medical condition occurring at any time after the 
time of randomization and/or treatment assignment, including baseline or washout periods, even 
if no study treatment has been administered.  (See Section 10.6.3 for information about AE 
collecting and reporting.)  
10.6.1.2. Serious Adverse Event (SAE) 
Any untoward medical occurrence that, at any dose; 
 Results in death;  
 Is life threatening (i.e., an event in which the patient was at risk of death at the time of the 
event; it does not refer to an event that hypothetically might have caused death if it were 
more severe);  
 Requires inpatient hospitalization* or prolongation of existing hospitalization;  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 141 of 259 
 
 Results in persistent or significant disability/incapacity;  
 Is a congenital anomaly/birth defect; or 
 Is an important medical event** 
 
*Exception: Preplanned (at time of informed consent) hospitalization for elective procedures, for 
protocol compliance or social reasons, or for observation will not be considered criteria for an 
SAE. The reason for the planned hospitalization should be captured in medical history section in 
the eCRF. Complications experienced during these hospitalizations must be reported as AEs (or 
SAEs, if hospitalization is prolonged due to the AE).  
 
**Medical and scientific judgment should be exercised in determining whether situations or 
events should be considered serious adverse events:  an important medical event may not be 
immediately life-threatening or result in death or require hospitalization but may jeopardize the 
patient or require intervention to prevent one of the above outcomes.  Examples of such events 
are allergic bronchospasm, blood dyscrasias, or convulsions that may require intensive treatment 
in an emergency room or at home but do not result in hospitalization, development of drug 
dependency or drug abuse, and transmission of disease associated with the administration of the 
study drug. (See Section 10.6.5 for information about SAE reporting.)  
10.6.1.3. Treatment-Emergent Adverse Event (TEAE) 
Any event that was not present prior to the initiation of study treatment or any event already 
present that worsens in either intensity or frequency following exposure to study treatment. 
10.6.1.4. Adverse Event of Special Interest (AESI) 
Any AE (serious or non-serious) that is of scientific and medical concern specific to the study 
treatment, for which ongoing monitoring and rapid communication by the Investigator to the 
Sponsor is appropriate. AESIs are described in Section 10.6.7. 
10.6.1.5. Special Situations: Abuse, Misuse, Medication Errors, Overdose, and Accidental 
or Occupational Exposure 
 Abuse:  is the persistent or sporadic, intentional excessive use of the study treatment 
which is accompanied by harmful physical or psychological effects.  
 Misuse: medicinal product is intentionally and inappropriately used not in accordance 
with the authorized/approved product information. 
 Medication error:  is any preventable incident that may cause or lead to 
inappropriate study treatment use or patient harm while the study treatment is in the 
control of the health care professionals or patients. Such incident may be due to 
health care professional practice, product labeling, packaging and preparation, 
procedures for administration, and systems, including the following: prescribing, 
order communication, nomenclature, compounding, dispensing, distribution, 
administration, education, monitoring, and use. 
 Overdose:  is a deliberate or accidental administration of study treatment to a study 
patient, at a dose greater than that which was assigned to that patient per the study 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 142 of 259 
 
protocol and under the direction of the Investigator.  If an overdose occurs, the 
Investigator and the Sponsor should be notified immediately, and the patient should 
be observed closely for AEs. Associated AEs should be treated and monitored by the 
Investigator. The dosage of study drug administered, any associated AEs, and/or 
treatment provided to the patient because of the overdose, should be documented on 
the applicable sections within the eCRF. An overdose (including an AE or SAE 
resulting from the overdose, if any) will be reported as described in Section 10.6.5. 
 Accidental /Occupational exposure:  is the unintentional exposure to a study 
treatment as a result of one’s professional or non-professional occupation, or 
accidental exposure to a non-professional to whom exposure was not intended (i.e., 
study product given to wrong patient).  
Reporting Special Situations:  All occurrences of abuse, misuse, medication error, overdose, and 
accidental or occupational exposure with any study treatment must be reported on an SAE 
Report Form [or designated Special Form] to the Sponsor regardless of whether or not an AE or 
SAE has occurred. If the abuse, misuse, medication error, overdose, or accidental / occupational 
exposure is associated with an SAE, an SAE report form must be submitted to the Sponsor 
within 24 hours of awareness. If there is no AE or SAE, the occurrence must be submitted on the 
designated Special Form (indicate ‘no AE has occurred’) as soon as possible. 
10.6.2. 
Assessment of Adverse Events 
10.6.2.1. Severity Assessment 
All AEs will be assessed by the Investigator for severity* according to Common Terminology 
Criteria for Adverse Events (CTCAE) v4.03: 14 June 2010; National Institutes of Health (NIH), 
National Cancer Institute (NCI). The CTCAE severity grades 1 through 5 provide unique clinical 
descriptions of severity of each adverse event. The CTCAE v4.03 is available on the NCI/NIH 
website. 
Please note that there is a distinction between serious and severe AEs: Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Section 10.6.1.2.  For example, a mild 
degree of gastrointestinal bleeding requiring an overnight hospitalization for monitoring 
purposes may be considered an SAE but is not necessarily severe.  
10.6.2.2. Relationship to Study Intervention 
The Investigator must provide a causality assessment regarding the relationship of the event with 
the study drug and/or study procedure for all AEs. One of the following categories should be 
selected based on medical judgment, considering all contributing factors: 
 Related: A causal relationship between the medicinal product (and/or study procedures) 
and AE is a reasonable possibility. For example, the occurrence of the AE cannot be 
explained by other causative factors. The AE, however, can be explained by 
pharmacological effect of the medicinal product such as a similar event having been 
reported previously, alteration of the dose effect, or the timing or seriousness of the AE, 
etc. Positive rechallenge/dechallenge is supportive.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 143 of 259 
 
 Not Related: A causal relationship between the medicinal product (and/or study 
procedures) and AE is not a reasonable possibility: there is no temporal relationship 
between the medicinal product and event, or an alternative etiology is more reasonable.  
10.6.2.3. Expectedness 
The Sponsor will be responsible for determining whether an adverse event is ‘expected’ or 
‘unexpected’.  An AE will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information provided in the Reference Safety Information of 
the effective niraparib or TSR-042 Investigator Brochure (IB).  
For carboplatin, paclitaxel, or bevacizumab, the local approved product label should be 
consulted. 
10.6.3. 
Collection and Recording Adverse Events 
AEs may be volunteered spontaneously by the study patient, or discovered by the study staff 
during physical examinations or by asking an open, nonleading question such as, “How have you 
been feeling since your last study visit?” The Investigator will document the nature of AE, date 
of onset of the AE (and time, if known), date of outcome of the AE (and time, if known), 
severity of the AE, action taken with study drug as a result of the AE, assessment of the 
seriousness of the AE, and assessment of the causal relationship of the AE to study drug and/or 
study procedure. 
AEs, including laboratory abnormalities that are assessed as clinically significant or require 
intervention, should be described using a diagnosis whenever possible, rather than individual 
underlying signs and symptoms. When a clear diagnosis cannot be identified, each sign or 
symptom should be recorded as a separate AE. 
All SAEs will be collected from the signing of the ICF for this study through 90 days after the 
last dose of study drug (or to a minimum of 30 days post-treatment if the patient starts alternate 
anticancer therapy) and recorded in the eCRF. SAEs will also be reported on an SAE form as 
described in Section 10.6.5 of this protocol. SAEs considered by the Investigator to be related to 
study medication are reported until study closeout.   
All AEs, regardless of the source of identification (e.g., physical examination, laboratory 
assessment, ECG, or reported by patient), will be collected and recorded in the eCRF for each 
patient from the time of randomization and/or treatment assignment until 30 days after the last 
dose of study drug.   
Concomitant illnesses that existed before entry into the study will not be considered AEs unless 
the illness worsens during the Treatment Period. Pre-existing conditions will be recorded as 
Medical History in the eCRF and on the SAE Report Form. 
Disease progression is an efficacy criterion and is therefore not considered an AE or SAE (even 
if fatal). Disease progression should be reported within the eCRF. If AEs/SAEs occur in relation 
to disease progression that are not consistent with the natural progression of the patient’s disease, 
these AEs/SAEs must be reported per AE/SAE reporting requirements described in 
Section 10.6.5.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 144 of 259 
 
10.6.4. 
Follow-Up of Adverse Events 
All AEs experienced by a patient, regardless of the suspected causality, will be monitored until 
the AE or SAE has resolved, until any abnormal laboratory values have returned to baseline or 
normal levels, until stabilized with a satisfactory explanation for the changes observed, until the 
patient is lost to follow-up, or until the patient has died. 
If an Investigator becomes aware of an SAE after the specified follow-up period and considers 
the SAE related to the study drug, the Investigator should report the SAE to the Sponsor 
according to timelines for reporting SAEs described in Section 10.6.5. 
10.6.5. 
Reporting 
The Investigator or sub-investigator must report all SAEs, and all follow up information to the 
Sponsor on an SAE Report Form within 24 hours of becoming aware of the initial event or 
follow-up information. The Investigator must provide a causality assessment and must sign and 
date all SAE Report Forms.   
It is the responsibility of the Investigator to review source documentation and describe pertinent 
information on the SAE Report Form.  If supporting documentation is requested (e.g., hospital 
reports, consultant reports, death certificates, autopsy reports, etc.), the Investigator should 
highlight all relevant and pertinent information within such documents, ensure that any patient’s 
personal identifiers (including Medical Record number) are removed, and submit the documents 
with the SAE Form to the Sponsor. The Sponsor (or designee) will return a confirmation of 
receipt for all email reports (if received from other than a “no reply” domain) within 1 business 
day.  
After receipt of the initial report, the Sponsor (or designee) will review the information and, if 
necessary, contact the Investigator to obtain further information. The Investigator must promptly 
respond to queries from the Sponsor. 
10.6.6. 
Submission and Distribution of Serious Adverse Event Reports 
Per regulatory requirements, if an event is assessed by the Sponsor as a Serious Unexpected 
Adverse Reaction (SUSAR), it is the responsibility of the Sponsor to submit the SUSAR 
Regulatory Authorities according to applicable regulations. 
In addition, the SUSAR will be distributed to the Investigators/sites, utilizing a Council for 
International Organizations of Medical Sciences (CIOMS) report form, or the MedWatch 3500A 
form). The Investigator/site will submit a copy of the report to their respective Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) per the governing institutional 
requirements and in compliance with local laws and guidelines. 
10.6.7. 
Adverse Events of Special Interest 
10.6.7.1. Niraparib 
Adverse Events of Special Interest (AESI) for niraparib are the following:  
 Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) 
 Secondary cancers (new malignancies [other than MDS or AML]) 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 145 of 259 
 
 Pneumonitis 
 Embryo-fetal toxicity 
AESI should be collected and reported as follows: 
 MDS and AML along with other secondary cancers should be reported to the Sponsor 
throughout the Follow-up Assessment Period  
 Pneumonitis should be reported to the Sponsor through 90 days after the last dose of 
study drug (or until the start of alternate anticancer therapy, whichever occurs first). 
 Embryo-fetal toxicity should be reported as outlined in Section 10.6.8  
10.6.7.2. TSR-042 
No AESIs have been reported to date, therefore all SAEs assessed by the Investigator or Sponsor 
to be reasonably associated with the use of TSR-042 are considered to be unexpected and should 
be reported as described in Section 10.6.5.  
10.6.7.3. TSR-022 
No AESIs have been reported to date, therefore all SAEs assessed by the Investigator or Sponsor 
to be reasonably associated with the use of TSR-022 are considered to be unexpected and should 
be reported as described in Section 10.6.5. 
10.6.8. 
Pregnancy 
The Investigator must report all pregnancies and the outcomes to the Sponsor. The Sponsor has 
the responsibility to monitor the outcome of all pregnancies reported during the clinical study. 
Each pregnancy must be reported by the Investigator to the Sponsor on an Initial Pregnancy 
Report Form within 24 hours of becoming aware of the pregnancy. Pregnancy is not an AE, and 
therefore does not need to be reported as an AE in the eCRF unless there is a suspicion that the 
study drug may have interfered with the effectiveness of a contraceptive medication. The 
Investigator must follow-up all pregnancies, document the course and the outcome, and report 
this information to the Sponsor on a Pregnancy Outcome Report Form within 24 hours of 
becoming aware - even if the patient was withdrawn from the study or the study has finished. 
An elective abortion without complications should not be regarded as an AE, however, it should 
be reported as the outcome to the pregnancy on the Pregnancy Outcome Report Form. 
Therapeutic abortions should be reported as a treatment procedure; the reason for the therapeutic 
abortion should be reported on the Pregnancy Outcome Report Form and as an AE in the eCRF. 
Hospitalization for normal delivery of a healthy newborn should not be considered an SAE. 
Any SAE that occurs during pregnancy must be recorded on the Pregnancy Outcome Report 
Form, reported as an SAE on the SAE Report Form (e.g., maternal serious complications, 
therapeutic abortion, ectopic pregnancy, stillbirth, neonatal death, congenital anomaly, birth 
defect) and reported to the Sponsor within 24 hours. Hospitalization for normal delivery of a 
healthy newborn should not be considered an SAE.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 146 of 259 
 
10.6.9. 
Special Situations 
All occurrences of abuse, misuse, medication error, overdose, and accidental or occupational 
exposure with any study treatment must be reported on a Special Situations Report Form to the 
Sponsor within 5 calendar days of becoming aware of the occurrence, regardless of whether it is 
categorized as an AE. If the occurrence is associated with an SAE, an SAE Report Form, along 
with the Special Situations Report Form, must be submitted to the Sponsor within 24 hours of 
awareness.   
10.6.10. 
Clinical Laboratory Assessments 
The following laboratory variable will be determined in accordance with the schedule of events 
in (Section 11). These tests will be performed by the local laboratory at the clinical site. Details 
on sample collection, processing, and management for clinical laboratory assessments can be 
found in the Study Laboratory Manual. 
Any laboratory values assessed as clinically significant should be recorded as an AE. If SAE 
criteria are met or the laboratory abnormality is an AESI (see Section 10.6.7), the AE should be 
recorded and reported according to the SAE reporting process (see Section 10.6.5). 
Hematological testing may occur more frequently than is specified in Section 11.1 when 
additional testing is medically indicated per Investigator judgment or if the AE meets the criteria 
for niraparib dose modification (see Section 6.4.1.1). Additional tests may be performed at a 
laboratory facility other than the study site, but test results must be reported to the study site. The 
study site must keep a copy of test results with the patient’s study file, and the results must be 
entered into the eCRF. 
The following clinical laboratory assessments will be performed: 
 Complete blood count: 
 
 Hemoglobin 
 White blood cell count 
 Platelets 
 Differential white cell count 
 Mean corpuscular volume 
 Mean platelet volume (optional; 
Note: Although mean platelet volume 
collection is optional, it is highly 
encouraged, especially for patients 
with high-grade thrombocytopenia.) 
 Coagulation factors: 
 
 International normalized 
ratio 
 
 aPTT 
 
 Serum chemistry: 
 
 Sodium 
 Chloride 
 Amylase 
 Glucose (fasting at baseline) 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 147 of 259 
 
 Potassium 
 ALT 
 Total bilirubin 
 Total protein 
 Calcium 
 Creatinine 
 Alkaline phosphatase 
 Albumin 
 Magnesium 
 Urea or blood urea nitrogen 
 AST 
 Lactate dehydrogenase 
 Urinalysis: 
 
 Specific gravity 
 Ketones 
 Protein 
 Blood 
 Leukocyte esterase 
 Specific gravity 
 Glucose 
 Protein 
 Nitrite 
 
 Thyroid panel: thyroid stimulating hormone (TSH), triiodothyronine (T3) or free 
triiodothyronine (FT3), and free thyroxine (FT4) or equivalent tests if TSH, T3 or 
FT3, or FT4 are not available 
 Serum pregnancy testing/urine pregnancy testing 
 HBsAg and HCV ribonucleic acid testing (performed at screening only when 
medically indicated based on history and physical examination) 
10.6.11. 
Physical Examination and Vital Signs 
Physical examinations, including height (screening only), weight, and vital signs (blood pressure 
[BP], pulse, and temperature), will be performed in accordance with the schedule of events 
(Section 11). 
Any physical examination or vital signs assessed as clinically significant should be recorded as 
an AE or SAE. If SAE criteria are met or the abnormality is an AESI (see Section 10.6.7), the 
event should be recorded and reported according to the SAE reporting process (see 
Section 10.6.5). 
Vital signs will be measured in all patients and include BP, pulse rate, and temperature. Height 
and weight will be measured in all patients. Height will be measured at screening only. 
10.6.12. 
Eastern Cooperative Oncology Group Performance Status 
Performance status will be assessed using the ECOG scale (see Appendix C) in accordance with 
the schedule of events (Section 11). The same observer should assess performance status each 
time. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 148 of 259 
 
10.6.13. 
Additional Safety Assessments 
All patients will undergo ECGs in accordance with the schedule of events (Section 11). ECGs 
should be performed prior to any blood draws. Patients will be supine or in a semi-recumbent 
position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are 
recorded. 
Any ECG findings assessed as clinically significant should be recorded as an AE. If SAE criteria 
are met or the abnormality is an AESI (see Section 10.6.7), the AE should be recorded and 
reported according to the SAE reporting process (see Section 10.6.5). 
10.7. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics consist of those variables that are assessed at 
screening/baseline.  
10.7.1. 
Patient Eligibility 
Compliance with inclusion and exclusion criteria will be assessed as outlined in Section 7.1 and 
Section 7.2. 
10.7.2. 
Patient Demography 
Patient demography consists of age at screening, race, ethnicity, and sex. 
10.7.3. 
Disease History 
For disease history the following will be documented: 
 Date of first diagnosis 
 Tumor type 
 Stage at time of initial diagnosis 
 Histology and grade of disease at diagnosis and most recent biopsy if additional 
biopsy performed 
 Information on first anticancer treatment: 
 Intent (adjuvant, neoadjuvant, curative, and palliative)  
 Date of start of first treatment 
 Agents used in first treatment 
 Date of last dose of first treatment 
 Information on second and subsequent anticancer treatments: 
 Intent (adjuvant, neoadjuvant, curative, and palliative)  
 Dates of start of all subsequent treatments 
 Agents in all subsequent treatments 
 Dates of last dose of all subsequent treatments 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 149 of 259 
 
 Best response and toxicities (including hematologic AEs) for each prior anticancer 
treatment 
 Date of recurrence for each prior anticancer treatment 
10.7.4. 
Medical and Surgical History 
Major medical and surgical history, including medication history and history of 
thrombocytopenia, neutropenia, leukopenia, or anemia, will be collected. Details of any prior 
invasive malignancy will be collected. Medical and surgical history will be obtained by 
interviewing the patient or by reviewing the patient’s medical records. 
10.7.5. 
Previous and Concomitant Medications 
Previous and concomitant medication will be documented as described in Section 9.7. 
Medications will be coded using WHO Anatomical Therapeutic Chemical classification. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 150 of 259 
 
11. 
STUDY CONDUCT 
11.1. 
Schedule of Events 
The schedule of study procedures is provided in Table 17 and Table 18 for Part A, in Table 19 
and Table 20 for Part B, in Table 21 and Table 22 for Part C, in Table 23 and Table 24 for 
Part D, in Table 25 and Table 26 for Part E, in Table 27 and Table 28 for Part F, in Table 29 and 
Table 30 for Part G, in Table 31 and Table 32 for Part H, and in Table 33 and Table 34 for Part I. 
The detailed schedule for PK and ADA sampling and ECG assessments is provided in Table 35 
and Table 36 for Part A, in Table 37 and Table 38 for Part B, in Table 39 and Table 40 for 
Part C, in Table 41 and Table 42 for Part D, in Table 43 for Part E, in Table 44 for Part F, in 
Table 45 for Part G, in Table 46 for Part H, and in Table 47 for Part I. 
The detailed schedules of administration are provided for TSR-042 and niraparib combination 
treatment in Part A (Table 48); for TSR-042 and carboplatin-paclitaxel combination treatment in 
Part B (Table 49); for TSR-042, niraparib, and bevacizumab combination treatment in Part C 
(Table 50); for TSR-042, carboplatin-paclitaxel, and bevacizumab combination treatment in 
Part D (Table 51); for TSR-042 and carboplatin-pemetrexed combination treatment in Part E 
(Table 52); for TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment in Part F 
(Table 53); for TSR-042 and carboplatin–nab-paclitaxel in Part G (Table 54); for TSR-042, 
TSR-022, and carboplatin–nab-paclitaxel in Part H (Table 55); and for TSR-042, TSR-022, and 
carboplatin-paclitaxel in Part I (Table 56). 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 151 of 259 
Table 17: 
Schedule of Events - Part A - TSR-042 + Niraparib- Screening and Cycle 1 Through Cycle 4 
Cycle/Visit
a 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (optional)
b 
X 
 
 
 
 
 
 
Blood sample for exploratory biomarkers 
X 
X
c 
 
 
Xc 
 
 
Blood sample for PK and ADAs
d 
 
X 
X 
X 
X 
 
X 
Tumor assessment (RECIST v1.1)
e 
X
f 
 
 
 
 
 
 
Laboratory assessments 
Xf 
X
g 
X 
X 
X
h 
Xh 
Xh 
CBC
i 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
X
j 
 
 
 
 
 
X
k 
Serum tumor markers (if indicated)e 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalent
l 
X 
 
 
 
X 
 
X 
ECGd 
Xf 
X 
 
 
X 
 
 
Physical examination 
Xf 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 
Vital signs, height, and weight
m 
Xf 
X 
X 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 152 of 259 
Table 17: 
Schedule of Events - Part A - TSR-042 + Niraparib- Screening and Cycle 1 Through Cycle 4 (Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
n 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
o 
 
X 
 
 
X 
X 
X 
Niraparib study treatment dispensed/collectedo 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; 
FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST 
v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b Archival FFPE tumor tissue sample should be submitted within 30 days of patient’s first dose. 
c Obtained predose. 
d PK and ADA blood sampling and ECG assessment will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 35. On Day 1 of Cycles 1 and 2, ECG monitoring is to be done 30 minutes prior to and 2 hours after the 
niraparib dose.  
e Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
f Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, height, and weight, 
will be performed as described in Section 11.2.1. 
g If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
h May be done within 24 hours prior to the visit. 
i If dose interruption or modification of niraparib is required at any point on study because of hematologic toxicity, CBCs will be performed as described in Section 6.4.1.1. 
j For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed.  
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 
o See Table 48 for details of TSR‑042 and niraparib combination treatment administration in Part A. TSR-042 will be administered at a dose of 500 mg on Day 1 on Day 1 of 
every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for up to 2 years or until progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death.. Niraparib will be dispensed/collected on Day 1 of every 21-day cycle (Q3W). 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 153 of 259 
Table 18: 
Schedule of Events - Part A - TSR-042 + Niraparib - Cycle 5 Through End of Study 
Cycle/Visit
a 
Cycle 5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Blood sample for exploratory 
biomarkers 
 
 
 
X
c 
 
 
 
Blood sample for PK and ADAs
d 
X 
X 
X 
X
e 
Xe 
Xe 
 
Tumor assessment (RECIST v1.1)
f,g
 
X 
 
X 
X 
X 
X 
X 
Laboratory assessments 
Xh 
Xh 
Xh 
X 
X
i 
Xi 
X 
CBCj 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X
k 
X 
X 
 
Pregnancy test 
 
 
Xk 
 
Xi 
 
 
Serum tumor markers 
(if indicated) 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalentl 
 
Xk 
Xk 
X 
X 
 
 
ECGd 
X 
 
X 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
m 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
n 
X 
X 
X 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 154 of 259 
Table 18: 
Schedule of Events - Part A - TSR-042 + Niraparib - Cycle 5 Through End of Study (Continued) 
Cycle/Visit 
Cycle 5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
TSR-042 study treatment 
administered
o 
X 
 
X 
 
 
 
 
Niraparib study treatment 
dispensed/collectedo 
X 
X 
X 
X 
 
 
 
Survival assessment  
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; FT3 = free triiodothyronine; FT4 = free thyroxine; EOT = end of treatment; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 
weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c Obtained at End of Treatment visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever occurs first. 
d PK and ADA blood sampling and ECG assessment will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 36. On Day 1 of Cycles 5 and 11, ECG monitoring is to be done 30 minutes prior to the niraparib dose. 
e Blood sample for ADAs only. 
 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3 . Tumor assessments are to be performed 
within 1 week prior to Day 1 of Cycle 5. 
,g Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a patient 
discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate testing of serum tumor 
markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6 for the safety follow-up visits and survival assessment, respectively. 
h May be done within 24 hours prior to the visit. 
i Performed as described in Section 11.2.5. 
j If dose interruption and/or modification of niraparib is required at any point on study because of hematologic toxicity, CBCs will be performed as described in Section 6.4.1.1. 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post treatment are to be captured. In conjunction with the survival assessment, AESI (regardless of causality) and study-drug related 
SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
o See Table 48 for details of TSR-042 and niraparib combination treatment administration in Part A. TSR-042 will be administered at a dose of 500 mg on Day 1 on Day 1 of 
every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for up to 2 years or until progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death. Niraparib will be dispensed/collected on Day 1 of every 21-day cycle (Q3W). 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 155 of 259 
Table 19: 
Schedule of Events - Part B – TSR-042 + Carboplatin-Paclitaxel - Screening and Cycle 1 Through Cycle 4 
Cycle/Visit
a 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (optional)
b 
X 
 
 
 
 
 
 
Blood sample for exploratory biomarkers 
X 
X
c 
 
 
Xc 
 
 
Blood sample for PK and ADAs
d 
 
X 
X 
X 
X 
 
X 
Tumor assessment (RECIST v1.1)
e 
X
f 
 
 
 
 
 
 
Laboratory assessments 
Xf 
X
g 
X 
X 
X
h 
Xh 
Xh 
CBC 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
X
i 
 
 
 
 
 
X
j 
Serum tumor markers (if indicated)e 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalent
k 
X 
 
 
 
X 
 
X 
ECGd 
Xf 
 
 
 
 
 
 
Physical examination 
Xf 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 
Vital signs, height, and weight
l 
Xf 
X 
X 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 156 of 259 
Table 19: 
Schedule of Events - Part B – TSR-042 + Carboplatin-Paclitaxel - Screening and Cycle 1 Through Cycle 4 
(Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
m 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
n 
 
X 
 
 
X 
X 
X 
Carboplatin-paclitaxel study treatment administeredn 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FFPE = 
formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = 
Response Evaluation Criteria in Solid Tumors version 1.1; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b Archival FFPE tumor tissue sample should be submitted within 30 days of patient’s first dose. 
c Obtained predose. 
d PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and ADA blood sampling 
and ECG assessments are provided in Table 37 for Part B. 
e Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
f Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, weight, and height, 
will be performed as described in Section 11.2.1. 
g If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
h May be done within 24 hours prior to the visit. 
i For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
j Performed as described in Section 11.2.3. 
k If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
l Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only.  
m AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 
n See Table 49 for details of TSR-042 and carboplatin-paclitaxel combination treatment administration in Part B. TSR-042 will be administered at a dose of 500 mg on Day 1 of 
every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for up to 2 years or until progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death. Carboplatin and paclitaxel will be administered for 4 to 6 cycles as clinically indicated. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 157 of 259 
Table 20: 
Schedule of Events - Part B – TSR-042 + Carboplatin-Paclitaxel - Cycle 5 Through End of Study 
Cycle/Visit
a 
Cycle 5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Day
s)  
Day: 
Procedure 
1 
1 
1 
+7 Days Post- 
treatment 
30 ± 7 Days Post-
treatment 
90 ± 7 Days 
Post-treatment 
Blood sample for exploratory 
biomarkers 
 
 
 
X
c 
 
 
 
Blood sample for PK and ADAs
d 
X 
X 
X 
X
e 
Xe 
Xe 
 
Tumor assessment (RECIST v1.1)
f 
X 
 
X 
X
g 
Xg 
Xg 
Xg 
Laboratory assessments 
X
h 
Xh 
Xh 
X 
X
i 
Xi 
X 
CBC 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X
j 
X 
X 
 
Pregnancy test 
 
 
X 
 
Xi 
 
 
Serum tumor markers (if 
indicated)f 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalent
k 
 
Xj 
Xj 
X 
X 
 
 
ECGd 
 
 
 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
l 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 158 of 259 
Table 20: 
Schedule of Events - Part B – TSR-042 + Carboplatin-Paclitaxel - Cycle 5 Through End of Study (Continued) 
Cycle/Visit 
Cycle 
5 
Cycle 
6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
 
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
 
AE monitoring
m 
X 
X 
X 
X 
X 
X 
X 
 
TSR-042 study treatment 
administered
n 
X 
 
X 
 
 
 
 
 
Carboplatin-paclitaxel study 
treatment administeredn 
X 
X 
 
 
 
 
 
 
Survival assessment 
 
 
 
 
 
 
X 
 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; FT3 = free triiodothyronine; FT4 = free thyroxine; EOT = end of treatment; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 
6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 
21 days (±3 days) until study treatment discontinuation. 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c Obtained at EOT visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever occurs first. 
d PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 38 for Part B. 
e Blood sample for ADAs only. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are 
to be performed within 1 week prior to Day 1 of Cycle 5 and every 12 weeks (84 ± 10 days) thereafter until progression while on study treatment, independent 
of cycle delays or dose interruptions, or at any time when progression of disease is suspected. 
g Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a 
patient discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6for the safety follow-up visits 
and survival assessment, respectively. 
h May be done within 24 hours prior to the visit. 
i Performed as described in Section 11.2.5. 
j Performed as described in Section 11.2.3. 
k If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other 
cycle thereafter. 
l Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
m AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after 
cessation of study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 159 of 259 
described in Section 10.6.7, and any pregnancies that occur within 180 days post treatment are to be captured. In conjunction with the survival assessment, 
AESI (regardless of causality) and study-drug related SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
n See Table 49 for details of TSR-042 and carboplatin-paclitaxel combination treatment administration in Part B. TSR-042 will be administered at a dose of 500 
mg on Day 1 of every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for up to 2 years or 
until progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Carboplatin and paclitaxel will be administered for 4 to 6 cycles 
as clinically indicated. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 160 of 259 
Table 21: 
Schedule of Events - Part C - TSR-042 + Niraparib + Bevacizumab - Screening and Cycle 1 Through Cycle 4 
Cycle/Visit
a 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (optional)
b 
X 
 
 
 
 
 
 
Blood sample for exploratory biomarkers 
X 
X
c 
 
 
Xc 
 
 
Blood sample for PK and ADAs
d 
 
X 
X 
X 
X 
 
X 
Tumor assessment (RECIST v1.1)
e 
X
f 
 
 
 
 
 
 
Laboratory assessments 
Xf 
X
g 
X 
X 
X
h 
Xh 
Xh 
CBC
i 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
X
j 
 
 
 
 
 
X
k 
Serum tumor markers (if indicated)e 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalent
l 
X 
 
 
 
X 
 
X 
ECGd 
Xf 
X 
 
 
X 
 
 
Physical examination 
Xf 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 
Vital signs, height, and weight
m 
Xf 
X 
X 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 161 of 259 
Table 21: 
Schedule of Events - Part C - TSR-042 + Niraparib + Bevacizumab - Screening and Cycle 1 Through Cycle 4 
(Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
n 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
o 
 
X 
 
 
X 
X 
X 
Niraparib study treatment dispensed/collectedo 
 
X 
 
 
X 
X 
X 
Bevacizumabo 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FFPE = 
formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = 
Response Evaluation Criteria in Solid Tumors version 1.1; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. 
b Archival FFPE tumor tissue sample should be submitted within 30 days of patient’s first dose. 
c Obtained predose. 
d PK and ADA blood sampling and ECG assessment will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 39 for Part C. On Day 1 of Cycles 1 and 2, ECG monitoring is to be done 30 minutes prior to and 2 hours after 
the niraparib dose.  
e Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
f Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, height, and weight, 
will be performed as described in Section 11.2.1. 
g If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
h May be done within 24 hours prior to the visit. 
i If dose interruption or modification of niraparib is required at any point on study because of hematologic toxicity, CBCs will be performed as described in Section 6.4.1.1. 
j For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.3) are required to be captured through 90 days after cessation of 
study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, 
and any pregnancies that occur within 180 days post‑treatment are to be captured. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 162 of 259 
o See Table 50 for details of TSR‑042, niraparib, and bevacizumab combination treatment administration in Part C. TSR-042 will be administered at a dose of 500 mg on Day 1 of 
every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for up to 2 years or until disease progression, 
unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Niraparib will be dispensed/collected on Day 1 of every 21-day cycle (Q3W). Bevacizumab will be 
administered at a dose of 15 mg/kg on Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 163 of 259 
Table 22: Schedule of Events - Part C – TSR-042 + Niraparib + Bevacizumab - Cycle 5 Through End of Study 
Cycle/Visit
a 
Cycle 5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Blood sample for exploratory 
biomarkers 
 
 
 
X
c 
 
 
 
Blood sample for PK and ADAs
d 
X 
X 
X 
X
e 
Xe 
Xe 
 
Tumor assessment (RECIST v1.1)
f,g 
X 
 
X 
X 
X 
X 
X 
Laboratory assessments 
X
h 
Xh 
Xh 
X
i 
Xi 
Xi 
Xi 
CBC
j 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X
k 
Xc 
X 
 
Pregnancy test 
 
 
Xk 
 
Xi 
 
 
Serum tumor markers 
(if indicated) 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalent
l 
 
Xk 
Xk 
X 
X 
 
 
ECGd 
X 
 
X 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
m 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
n 
X 
X 
X 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 164 of 259 
Table 22: 
Schedule of Events - Part C – TSR-042 + Niraparib + Bevacizumab - Cycle 5 Through End of Study (Continued) 
Cycle/Visita 
Cycle 5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Upb 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
TSR-042 study treatment 
administered
o 
X 
 
X 
 
 
 
 
Niraparib study treatment 
dispensed/collectedo 
X 
X 
X 
X 
 
 
 
Bevacizumab study treatment 
administeredo 
X 
X 
X 
 
 
 
 
Survival assessment  
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; FT3 = free triiodothyronine; FT4 = free thyroxine; EOT = end of treatment; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 
weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c Obtained at EOT visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever occurs first. 
d PK and ADA blood sampling and ECG assessment will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 40 for Part C. On Day 1 of Cycles 5 and 11, ECG monitoring is to be done 30 minutes prior to the niraparib 
dose.  
e Blood sample for ADAs only. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are to be performed 
within 1 week prior to Day 1 of Cycle 5. 
g Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a patient 
discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate testing of serum tumor 
markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6 for the safety follow-up visits and survival assessment, respectively. 
h May be done within 24 hours prior to the visit. 
i Performed as described in Section 11.2.5. 
j If dose interruption and/or modification of niraparib is required at any point on study because of hematologic toxicity, CBCs will be performed as described in Section 6.4.1.1. 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post treatment are to be captured. In conjunction with the survival assessment, AESI (regardless of causality) and study-drug related 
SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 165 of 259 
o See Table 50  for details of TSR-042, niraparib, and bevacizumab combination treatment administration in Part C. TSR-042 will be administered at a dose of 500 mg on Day 1 
of every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for up to 2 years or until progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death. Niraparib will be dispensed/collected on Day 1 of every 21-day cycle (Q3W). Bevacizumab will be administered at 
a dose of 15 mg/kg on Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 166 of 259 
Table 23: 
Schedule of Events - Part D – TSR-042 + Carboplatin-Paclitaxel + Bevacizumab - Screening and Cycle 1 
Through Cycle 4 
Cycle/Visit
a 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (optional)
b 
X 
 
 
 
 
 
 
Blood sample for exploratory biomarkers 
X 
X
c 
 
 
Xc 
 
 
Blood sample for PK and ADAs
d 
 
X 
X 
X 
X 
 
X 
Tumor assessment (RECIST v1.1)
e 
X
f 
 
 
 
 
 
 
Laboratory assessments 
Xf 
X
g 
X 
X 
Xh 
Xh 
Xh 
CBC 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
X
i 
 
 
 
 
 
X
j 
Serum tumor markers (if indicated)e 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalent
k 
X 
 
 
 
X 
 
X 
ECGd 
Xf 
 
 
 
 
 
 
Physical examination 
Xf 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 167 of 259 
Table 23: 
Schedule of Events - Part D – TSR-042 + Carboplatin-Paclitaxel + Bevacizumab - Screening and Cycle 1 
Through Cycle 4 (Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Vital signs, height, and weight
l 
Xf 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
m 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
n 
 
X 
 
 
X 
X 
X 
Carboplatin-paclitaxel study treatment administeredn 
 
X 
 
 
X 
X 
X 
Bevacizumab study treatment administeredn 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FFPE = 
formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = 
Response Evaluation Criteria in Solid Tumors version 1.1; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b Archival FFPE tumor tissue sample should be submitted within 30 days of patient’s first dose. 
c Obtained predose. 
d PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and ADA blood sampling 
and ECG assessments are provided in Table 41 for Part D. 
e Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
f Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, weight, and height, 
will be performed as described in Section 11.2.1. 
g If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
h May be done within 24 hours prior to the visit. 
i For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
j Performed as described in Section 11.2.3. 
k If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
l Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only.  
m AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 168 of 259 
n See Table 51 for details of TSR-042, carboplatin-paclitaxel, and bevacizumab combination treatment administration in Part D. TSR-042 will be administered at a dose of 500 mg 
on Day 1 of every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for up to 2 years or until disease 
progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Carboplatin and paclitaxel will be administered on Day 1 of every 21-day cycle (Q3W) 
for 4 to 6 cycles as clinically indicated. Bevacizumab will be administered at a dose of 15 mg/kg on Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 169 of 259 
Table 24: 
Schedule of Events - Part D – TSR-042 + Carboplatin-Paclitaxel + Bevacizumab -Cycle 5 Through End of Study 
Cycle/Visit
a 
Cycle 5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Blood sample for exploratory 
biomarkers 
 
 
X
c 
 
 
 
Blood sample for PK and ADAs
d 
X 
X 
X 
X
e 
Xe 
Xe 
 
Tumor assessment (RECIST v1.1)
f 
X 
 
X 
X
g 
Xg 
Xg 
Xg 
Laboratory assessments 
X
h 
Xh 
Xh 
X 
X
i 
Xi 
X 
CBC 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X
j 
X 
X 
 
Pregnancy test 
 
 
Xj 
 
Xi 
 
 
Serum tumor markers (if 
indicated)f 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalent
k 
 
Xj 
Xj 
X 
X 
 
 
ECGd 
 
 
 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
l 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
m 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment 
administered
n 
X 
 
X 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 170 of 259 
Table 24: 
Schedule of Events - Part D – TSR-042 + Carboplatin-Paclitaxel + Bevacizumab -Cycle 5 Through End of Study 
(Continued) 
Cycle/Visit 
Cycle 5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Carboplatin-paclitaxel study 
treatment administeredn 
X 
X 
 
 
 
 
 
Bevacizumab study treatment 
administeredn 
X 
X 
X 
 
 
 
 
Survival assessment 
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; FT3 = free triiodothyronine; FT4 = free thyroxine; EOT = end of treatment; PK = pharmacokinetics; Q3W = every 3 weeks; 
Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; TSH = thyroid-
stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 
21 days (±3 days) until study treatment discontinuation. 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c Obtained at End of Treatment visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever 
occurs first. 
d PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 42 for Part D. 
e Blood sample for ADAs only. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are 
to be performed within 1 week prior to Day 1 of Cycle 5. 
g Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a 
patient discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6 for the safety follow-up visits 
and survival assessment, respectively. 
h May be done within 24 hours prior to the visit. 
i Performed as described in Section 11.2.5. 
j Performed as described in Section 11.2.3. 
k If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other 
cycle thereafter. 
l Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 171 of 259 
m AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after 
cessation of study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as 
described in Section 10.6.7, and any pregnancies that occur within 180 days post‑treatment are to be captured.. In conjunction with the survival assessment, 
AESI (regardless of causality) and study-drug related SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
n See Table 51 for details of TSR-042, carboplatin-paclitaxel, and bevacizumab combination treatment administration in Part D. TSR-042 will be administered at 
a dose of 500 mg on Day 1 of every cycle (Q3W) for 4 cycles, followed by 1,000 mg beginning on Cycle 5 Day 1 and every other cycle (Q6W) thereafter for 
up to 2 years or until progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Carboplatin and paclitaxel will be administered 
for 4 to 6 cycles as clinically indicated. Bevacizumab will be administered at a dose of 15 mg/kg on Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 172 of 259 
Table 25: 
Schedule of Events - Part E – TSR-042 + Carboplatin-Pemetrexed - Screening and Cycle 1 Through Cycle 4 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (optional)b 
X 
 
 
 
 
 
 
Serial tumor tissue biopsy (optional)c 
 
 
 
 
4 to 6 weeks following Dose 1  
Blood sample for exploratory biomarkers 
X 
Xd 
 
Xd 
Xd 
 
Xd 
Blood sample for PK and ADAs
e 
 
X 
X 
X 
X 
 
  
Tumor assessment (RECIST v1.1)
f 
X
g 
 
 
 
 
 
 
Laboratory assessments 
Xg 
Xh 
X 
X 
Xi 
Xi 
Xi 
CBC 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
Xj 
 
 
 
 
 
Xk 
Serum tumor markers (if indicated)f 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalentl 
X 
 
 
 
X 
 
X 
ECGe 
Xg 
 
 
 
 
 
 
Physical examination 
Xg 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 
Vital signs, height, and weightm 
Xg 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoringn 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
o 
 
X 
 
 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 173 of 259 
Table 25: 
Schedule of Events - Part E – TSR-042 + Carboplatin-Pemetrexed - Screening and Cycle 1 Through Cycle 4 
(Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Pemetrexed study treatment administeredo 
 
X 
 
 
X 
X 
X 
Carboplatin study treatment administeredo 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = 
every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; TSH = 
thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b The archival FFPE tumor tissue sample (optional) should be submitted within 30 days of patient’s first dose.  
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever possible, at the time 
of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are provided in the Study Laboratory 
Manual).  
d Obtained predose. 
e PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and ADA blood sampling 
and ECG assessments are provided in Table 43 for Part E. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
g Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, weight, and height, 
will be performed as described in Section 11.2.1. 
h If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
i May be done within 24 hours prior to the visit. 
j For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only.  
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 
o See Table 52 for details of TSR-042 and carboplatin-pemetrexed combination treatment administration in Part E. TSR-042 will be administered at a dose of 500 mg on Day 1 of 
every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Pemetrexed will be administered on 
Day 1 Q3W for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Carboplatin will be administered on Day 1 of every 
21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 174 of 259 
Table 26: 
Schedule of Events - Part E – TSR-042 + Carboplatin-Pemetrexed - Cycle 5 Through End of Study 
Cycle/Visit
a 
Cycle 5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days Post- 
treatment 
30 ± 7 Days Post-
treatment 
90 ± 7 Days 
Post-treatment 
Serial tumor tissue biopsy (optional)
c 
 
 
 
X
d 
 
 
 
Blood sample for exploratory biomarkers 
 
X
e 
 
Xd 
 
 
 
Blood sample for PK and ADAs
f 
X 
X 
X
g 
Xg 
Xg 
 
Tumor assessment (RECIST v1.1)
h 
X 
 
X 
X
i 
Xi 
Xi 
Xi 
Laboratory assessments 
X
j 
Xj 
Xj 
X 
X
k 
Xk 
X 
CBC 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X 
X 
X 
 
Pregnancy test 
 
 
X
l 
 
Xk 
 
 
Serum tumor markers (if indicated)h 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 or equivalent
m 
 
Xl 
Xl 
X 
X 
 
 
ECGf 
 
 
 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
n 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
o 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
p 
X 
X 
X 
 
 
 
 
Pemetrexed study treatment administeredp 
X 
X 
X 
 
 
 
 
Carboplatin study treatment administeredp 
X 
X 
 
 
 
 
 
Survival assessment 
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = 
end of treatment; FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 
weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 
21 days (±3 days) until study treatment discontinuation. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 175 of 259 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever 
possible, at the time of disease progression (EOT visit) as described in Section 10.4 (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy 
is recommended (details are provided in the Study Laboratory Manual). 
d Obtained at EOT visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever occurs first. 
e Obtained predose. 
f PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 43 for Part E. 
g Blood sample for ADAs only. 
h Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are 
to be performed within 1 week prior to Day 1 of Cycle 5. 
i Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a 
patient discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals as described in Section 11.2.5and Section 11.2.6 for the safety follow-up visits 
and survival assessment, respectively. 
j May be done within 24 hours prior to the visit. 
k Performed as described in Section 11.2.5. 
l Performed as described in Section 11.2.3. 
m If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other 
cycle thereafter. 
n Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
o AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after 
cessation of study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as 
described in Section 10.6.7, and any pregnancies that occur within 180 days post‑treatment are to be captured. In conjunction with the survival assessment, 
AESI (regardless of causality) and study-drug related SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
p See Table 52 for details of TSR-042 and carboplatin-pemetrexed combination treatment administration in Part E. TSR-042 will be administered at a dose of 
500 mg on Day 1 of every cycle (Q3W)  for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or 
death. Pemetrexed will be administered on Day 1 Q3W for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s 
decision, or death. Carboplatin will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 176 of 259 
Table 27: 
Schedule of Events - Part F – TSR-042 + TSR-022 + Carboplatin-Pemetrexed - Screening and Cycle 1 Through 
Cycle 4 
Cycle/Visit
a 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (mandatory, if 
available)b 
X 
 
 
 
 
 
 
Serial tumor tissue biopsy (optional)c 
 
 
 
 
4 to 6 weeks following Dose 1 
Blood sample for exploratory biomarkers 
X 
Xd 
 
Xd 
Xd 
 
Xd 
Blood sample for PK and ADAs
e 
 
X 
X 
X 
X 
 
  
Tumor assessment (RECIST v1.1)
f 
X 
 
 
 
 
 
 
Laboratory assessments 
X
g 
X
h 
X 
X 
Xi 
Xi 
Xi 
CBC 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
Xj 
 
 
 
 
 
Xk 
Serum tumor markers (if indicated)f 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalentl 
X 
 
 
 
X 
 
X 
ECGe 
Xg 
 
 
 
 
 
 
Physical examination 
Xg 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 177 of 259 
Table 27: 
Schedule of Events - Part F – TSR-042 + TSR-022 + Carboplatin-Pemetrexed - Screening and Cycle 1 Through 
Cycle 4 (Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Vital signs, height, and weightm 
Xg 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoringn 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administeredo 
 
X 
 
 
X 
X 
X 
TSR-022 study treatment administeredo 
 
X 
 
 
X 
X 
X 
Pemetrexed study treatment administeredo 
 
X 
 
 
X 
X 
X 
Carboplatin study treatment administeredo 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = every 3 
weeks; Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; TSH = thyroid-
stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b Mandatory submission of archival FFPE tumor tissue sample, if available, should be within 30 days of patient’s first dose. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever possible, at the time 
of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are provided in the Study Laboratory 
Manual). 
d Obtained predose. 
e PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and ADA blood sampling 
and ECG assessments are provided in Table 44 for Part F. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
g Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, weight, and height, 
will be performed as described in Section 11.2.1. 
h If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
i May be done within 24 hours prior to the visit. 
j For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 178 of 259 
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 
o See Table 53 for details of TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment administration in Part F. TSR-042 will be administered at a dose of 500 mg 
on Day 1 of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. TSR-022 will be 
administered at a dose of 900 mg on Day 1 Q3W for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
Pemetrexed will be administered on Day 1 Q3W for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Carboplatin 
will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated.  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 179 of 259 
Table 28: 
Schedule of Events - Part F – TSR-042 + TSR-022 + Carboplatin-Pemetrexed - Cycle 5 Through End of Study 
Cycle/Visita 
Cycle 
5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Upb 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Serial tumor tissue biopsy (optional)c 
 
 
 
Xd 
 
 
 
Blood sample for exploratory 
biomarkers 
 
X
e 
 
Xd 
 
 
 
Blood sample for PK and ADAse,f 
X 
 
  
X
g 
Xg 
Xg 
 
Tumor assessment (RECIST v1.1)
h, i 
X 
 
X 
X 
X 
X 
X 
Laboratory assessments 
X
j 
Xj 
Xj 
X 
X
k 
Xk 
X 
CBC 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X 
X 
X 
 
Pregnancy test 
 
 
X
l 
 
Xk 
Xk 
 
Serum tumor markers (if indicated) 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalent
m 
 
Xl 
Xl 
X 
X 
 
 
ECGf 
 
 
 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
n 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
o 
X 
X 
X 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 180 of 259 
Table 28: 
Schedule of Events - Part F – TSR-042 + TSR-022 + Carboplatin-Pemetrexed - Cycle 5 Through End of Study 
(Continued) 
Cycle/Visita 
Cycle 
5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Upb 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
TSR-042 study treatment  
administered
p 
X 
X 
X 
 
 
 
 
TSR-022 study treatment 
administeredp 
X 
X 
X 
 
 
 
 
Pemetrexed study treatment 
administeredp 
X 
X 
X 
 
 
 
 
Carboplatin study treatment 
administeredp 
X 
X 
 
 
 
 
 
Survival assessment 
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FT3 = free triiodothyronine; FT4 = free thyroxine; EOT = end of treatment; PK = 
pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious 
adverse event; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 
21 days (±3 days) until study treatment discontinuation. 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever 
possible, at the time of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are 
provided in the Study Laboratory Manual). 
d Obtained at End of Treatment visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever 
occurs first. 
e Obtained predose. 
f PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 44 for Part F. 
g Blood sample for ADAs only. 
h Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are 
to be performed within 1 week prior to Day 1 of Cycle 5. 
i Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a 
patient discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 181 of 259 
testing of serum tumor markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6 for the safety follow-up visits 
and survival assessment, respectively. 
j May be done within 24 hours prior to the visit. 
k Performed as described in Section 11.2.5. 
l Performed as described in Section 11.2.3. 
m If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other 
cycle thereafter. 
n Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
o AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after 
cessation of study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as 
described in Section 10.6.7, and any pregnancies that occur within 180 days post treatment are to be captured. In conjunction with the survival assessment, 
AESI (regardless of causality) and study-drug related SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
p See Table 53 for details of TSR-042, TSR-022, and carboplatin-pemetrexed combination treatment administration in Part F. TSR-042 will be administered at a 
dose of 500 mg on Day 1 of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, 
or death. TSR-022 will be administered at a dose of 900 mg on Day 1 Q3W for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. Pemetrexed will be administered on Day 1 Q3W for up to 2 years or until progression or toxicity. Carboplatin 
will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 182 of 259 
Table 29: 
Schedule of Events - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - Screening and Cycle 1 Through Cycle 4 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (optional)b 
X 
 
 
 
 
 
 
Serial tumor tissue biopsy (optional)c 
 
 
 
 
4 to 6 weeks following Dose 1  
Blood sample for exploratory biomarkers 
X 
Xd 
 
Xd 
Xd 
 
Xd 
Blood sample for PK and ADAse 
 
X 
X 
X 
X 
 
  
Tumor assessment (RECIST v1.1)f 
X 
 
 
 
 
 
 
Laboratory assessments 
X
g 
X
h 
X 
X 
Xi 
Xi 
Xi 
CBC 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
Xj 
 
 
 
 
 
Xk 
Serum tumor markers (if indicated)f 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalentl 
X 
 
 
 
X 
 
X 
ECGe 
Xg 
 
 
 
 
 
 
Physical examination 
Xg 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 
Vital signs, height, and weight
m 
Xg 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
n 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
o 
 
X 
 
 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 183 of 259 
Table 29: 
Schedule of Events - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - Screening and Cycle 1 Through Cycle 4 
(Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Nab-paclitaxel study treatment - administered on Day 
1 of each weeko 
 
X 
X 
X 
X 
X 
X 
Carboplatin study treatment administeredo 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; 
Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; 
TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1. Visits for subsequent cycles continue every 21 days (±3 days) until study treatment 
discontinuation. Nab‑paclitaxel will also be administered on Day 1 of each week (Q1W). 
b The archival FFPE tumor tissue sample (optional) should be submitted within 30 days of patient’s first dose.  
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever possible, at the time 
of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are provided in the Study Laboratory 
Manual).  
d Obtained predose. 
e PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and ADA blood sampling 
and ECG assessments are provided in Table 45 for Part G. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
g Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, weight, and height, 
will be performed as described in Section 11.2.1. 
h If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
i May be done within 24 hours prior to the visit. 
j For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only.  
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 
o See Table 54 for details of TSR-042 and carboplatin–nab‑paclitaxel combination treatment administration in Part G. TSR-042 will be administered at a dose of 500 mg on Day 1 
of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. Nab-paclitaxel will be 
administered on Days 1, 8, and 15 (Q1W) of every 3-week cycle for 4 to 6 cycles as clinically indicated. Carboplatin will be administered on Day 1 of every 21-day cycle (Q3W) 
for 4 to 6 cycles as clinically indicated. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 184 of 259 
Table 30: 
Schedule of Events - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - Cycle 5 Through End of Study 
Cycle/Visit
a 
Cycle 
5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days Post- 
treatment 
30 ± 7 Days Post-
treatment 
90 ± 7 Days 
Post-treatment 
Serial tumor tissue biopsy (optional)
c  
 
 
 
X
d 
 
 
 
Blood sample for exploratory 
biomarkers 
 
X
e 
 
Xd 
 
 
 
Blood sample for PK and ADAs
f 
X 
X 
X
g 
Xg 
Xg 
 
Tumor assessment (RECIST v1.1)
h 
X 
 
X 
X
i 
Xi 
Xi 
Xi 
Laboratory assessments 
X
j 
Xj 
Xj 
X 
X
k 
Xk 
X 
CBC 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X 
X 
X 
 
Pregnancy test 
 
 
X
l 
 
Xk 
 
 
Serum tumor markers (if  
indicated)h 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalent
m 
 
Xl 
Xl 
X 
X 
 
 
ECGf 
 
 
 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
n 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
o 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
p 
X 
X 
X 
 
 
 
 
Nab-paclitaxel study treatment - 
administered on Day 1 of each weekp 
X 
X 
X 
 
 
 
 
Carboplatin study treatment 
administeredp 
X 
X 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 185 of 259 
Table 30: 
Schedule of Events - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - Cycle 5 Through End of Study 
(Continued) 
Cycle/Visit 
Cycle 
5 
Cycle 6 
Subsequent 
Cycles 
EOT 
Safety Follow-Up 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days Post- 
treatment 
30 ± 7 Days Post-
treatment 
90 ± 7 Days 
Post-treatment 
Survival assessment 
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; 
EOT = end of treatment; FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; Q3W = every 3 weeks; 
Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1. Visits for subsequent cycles continue every 21 days (±3 days) until study 
treatment discontinuation.  
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever 
possible, at the time of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are 
provided in the Study Laboratory Manual). 
d Obtained at EOT visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever occurs first. 
e Obtained predose. 
f PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 45 for Part G. 
g Blood sample for ADAs only. 
h Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are 
to be performed within 1 week prior to Day 1 of Cycle 5. 
i Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a 
patient discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6 for the safety follow-up visits 
and survival assessment, respectively. 
j May be done within 24 hours prior to the visit. 
k Performed as described in Section 11.2.5. 
l Performed as described in Section 11.2.3. 
m If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other 
cycle thereafter. 
n Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
o AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after 
cessation of study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 186 of 259 
described in Section 10.6.7, and any pregnancies that occur within 180 days post‑treatment are to be captured. In conjunction with the survival assessment, 
AESIs (regardless of causality) and study-drug related SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
p See Table 54 for details of TSR-042 and nab-paclitaxel combination treatment administration in Part G. TSR-042 will be administered at a dose of 500 mg on 
Day 1 of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
Nab-paclitaxel will be administered on Days 1, 8, and 15 (Q1W) of every 3-week cycle for 4 to 6 cycles as clinically indicated. Carboplatin will be 
administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 187 of 259 
Table 31: 
Schedule of Events - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-Paclitaxel - Screening and Cycle 1 
Through Cycle 4 
Cycle/Visit
a 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue (mandatory, if available)b 
X 
 
 
 
 
 
 
Serial tumor tissue biopsy (optional)c 
 
 
 
 
4 to 6 weeks following Dose 1 
Blood sample for exploratory biomarkers 
X 
Xd 
 
Xd 
Xd 
 
Xd 
Blood sample for PK and ADAse 
 
X 
X 
X 
X 
 
  
Tumor assessment (RECIST v1.1)f 
X 
 
 
 
 
 
 
Laboratory assessments 
X
g 
X
h 
X 
X 
Xi 
Xi 
Xi 
CBC 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
Xj 
 
 
 
 
 
X
k 
Serum tumor markers (if indicated)f 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalent
l 
X 
 
 
 
X 
 
X 
ECGe 
Xg 
 
 
 
 
 
 
Physical examination 
Xg 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 188 of 259 
Table 31: 
Schedule of Events - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-Paclitaxel - Screening and Cycle 1 
Through Cycle 4 (Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Vital signs, height, and weight
m 
Xg 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
n 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
o 
 
X 
 
 
X 
X 
X 
TSR-022 study treatment administeredo 
 
X 
 
 
X 
X 
X 
Nab-paclitaxel study treatment - administered on Day 
1 of each weeko 
 
X 
X 
X 
X 
X 
X 
Carboplatin study treatment administeredo 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; 
Q1W = every week; Q3W = every 3 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; 
TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1. Visits for subsequent cycles continue every 21 days (±3 days) until study treatment 
discontinuation. Nab-paclitaxel will also be administered on Day 1 of each week (Q1W). 
b Mandatory submission of archival FFPE tumor tissue sample, if available, should be within 30 days of patient’s first dose. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever possible, at the time 
of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are provided in the Study Laboratory 
Manual). 
d Obtained predose. 
e PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and ADA blood sampling 
and ECG assessments are provided in Table 46 for Part H. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
g Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, weight, and height, 
will be performed as described in Section 11.2.1. 
h If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
i May be done within 24 hours prior to the visit. 
j For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 189 of 259 
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 
o See Table 55 for details of TSR-042, TSR-022, and carboplatin–nab-paclitaxel combination treatment administration in Part H. TSR-042 will be administered at a dose of 
500 mg on Day 1 of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. TSR-022 will 
be administered at a dose of 900 mg on Day 1 Q3W for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
Nab-paclitaxel will be administered on Days 1, 8, and 15 (Q1W) of every 3-week cycle for 4 to 6 cycles as clinically indicated. Carboplatin will be administered on Day 1 of 
every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated.  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 190 of 259 
Table 32: 
Schedule of Events - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-Paclitaxel - Cycle 5 Through End of 
Study 
Cycle/Visit
a 
Cycle 
5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Serial tumor tissue biopsy (optional)
c 
 
 
 
X
d 
 
 
 
Blood sample for exploratory 
biomarkers 
 
X
e 
 
Xd 
 
 
 
Blood sample for PK and ADAs
f 
X 
X 
  
X
g 
Xg 
Xg 
 
Tumor assessment (RECIST v1.1)
h 
X 
 
X 
X
i 
Xi 
Xi 
Xi 
Laboratory assessments 
X
j 
Xj 
Xj 
X 
X
k 
Xk 
X 
CBC 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X 
X 
X 
 
Pregnancy test 
 
 
X
l 
 
Xk 
 
 
Serum tumor markers (if indicated)h 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalent
m 
 
Xl 
Xl 
X 
X 
 
 
ECGf 
 
 
 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
n 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
o 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
p 
X 
X 
X 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 191 of 259 
Table 32: 
Schedule of Events - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-Paclitaxel - Cycle 5 Through End of 
Study (Continued) 
Cycle/Visita 
Cycle 
5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Upb 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
TSR-022 study treatment 
administeredp 
X 
X 
X 
 
 
 
 
Nab-paclitaxel study treatment - 
administered on Day 1 of each weekp 
X 
X 
X 
 
 
 
 
Carboplatin study treatment 
administeredp 
X 
X 
 
 
 
 
 
Survival assessment 
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; FT3 = free triiodothyronine; FT4 = free thyroxine; EOT = end of treatment; PK = pharmacokinetics; Q3W = every 3 weeks; 
Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; TSH = thyroid-
stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1. Visits for subsequent cycles continue every 21 days (±3 days) until study 
treatment discontinuation. Nab-paclitaxel will also be administered on Day 1 of each week (Q1W). 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever 
possible, at the time of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are 
provided in the Study Laboratory Manual). 
d Obtained at End of Treatment visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever 
occurs first. 
e Obtained predose 
f PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 46 for Part H. 
g Blood sample for ADAs only. 
h Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are 
to be performed within 1 week prior to Day 1 of Cycle 5. 
i Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a 
patient discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6 for the safety follow-up visits 
and survival assessment, respectively. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 192 of 259 
j May be done within 24 hours prior to the visit. 
k Performed as described in Section 11.2.5. 
l Performed as described in Section 11.2.3. 
m If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other 
cycle thereafter. 
n Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
o AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after 
cessation of study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as 
described in Section 10.6.7, and any pregnancies that occur within 180 days post treatment are to be captured. In conjunction with the survival assessment, 
AESIs (regardless of causality) and study-drug related SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
p See Table 55 for details of TSR-042, TSR-022, and carboplatin–nab-paclitaxel combination treatment administration in Part H. TSR-042 will be administered 
at a dose of 500 mg on Day 1 of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s 
decision, or death. TSR-022 will be administered at a dose of 900 mg on Day 1 Q3W for up to 2 years or until disease progression, unacceptable toxicity, 
patient withdrawal, Investigator’s decision, or death. Nab-paclitaxel will be administered on Day 1 of every week (Q1W) for 4 to 6 cycles as clinically 
indicated. Carboplatin will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated.  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 193 of 259 
Table 33: 
Schedule of Events - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - Screening and Cycle 1 Through 
Cycle 4 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
Informed consent 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria review 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical, surgical, cancer, and medication history 
X 
 
 
 
 
 
 
Archival FFPE tumor tissue sample (mandatory, if 
available)b 
X 
 
 
 
 
 
 
Serial tumor tissue biopsy (optional)
c 
 
 
 
 
4 to 6 weeks following Dose 1 
Blood sample for exploratory biomarkers 
X 
X
d 
 
Xd 
Xd 
 
Xd 
Blood sample for PK and ADAs
e 
 
X 
X 
X 
X 
 
  
Tumor assessment (RECIST v1.1)
f 
X 
 
 
 
 
 
 
Laboratory assessments 
X
g 
X
h 
X 
X 
Xi 
Xi 
Xi 
CBC 
X 
X 
X 
X 
X 
X 
X 
Serum chemistry 
X 
X 
 
X 
X 
X 
X 
Coagulation 
X 
 
 
X 
X 
X 
 
Pregnancy test 
Xj 
 
 
 
 
 
Xk 
Serum tumor markers (if indicated)f 
X 
X 
 
 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
X 
X 
TSH, T3 or FT3, and FT4 or equivalent
l 
X 
 
 
 
X 
 
X 
ECGe 
Xg 
 
 
 
 
 
 
Physical examination 
Xg 
 
 
 
 
 
 
Symptom-directed physical examination 
 
X 
 
X 
X 
X 
X 
Vital signs, height, and weight
m 
Xg 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
 
 
 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
n 
X 
X 
X 
X 
X 
X 
X 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 194 of 259 
Table 33: 
Schedule of Events - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - Screening and Cycle 1 Through 
Cycle 4 (Continued) 
Cycle/Visita 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Day: 
Procedure 
-28 to -1 
1 
8 
15 
1 
1 
1 
TSR-042 study treatment administeredo 
 
X 
 
 
X 
X 
X 
TSR-022 study treatment administeredo 
 
X 
 
 
X 
X 
X 
Paclitaxel study treatment administeredo 
 
X 
 
 
X 
X 
X 
Carboplatin study treatment administeredo 
 
X 
 
 
X 
X 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; ECG = electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; FFPE = formalin-fixed paraffin embedded; FT3 = free triiodothyronine; FT4 = free thyroxine; PK = pharmacokinetics; 
Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious adverse event; T3 = triiodothyronine; 
TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 21 days (±3 days) 
until study treatment discontinuation. 
b Mandatory submission of archival FFPE tumor tissue sample, if available, should be submitted within 30 days of patient’s first dose. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever possible, at the time 
of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are provided in the Study Laboratory 
Manual). 
d Obtained predose. 
e PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and ADA blood sampling 
and ECG assessments are provided in Table 47 for Part I. 
f Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.1 and Section 11.2.3. 
g Standard of care tests/procedures, including radiographic scans, laboratory assessments (fasting glucose at baseline), ECG, physical examination, vital signs, weight, and height, 
will be performed as described in Section 11.2.1. 
h If screening laboratory testing (CBC, serum chemistry, serum tumor markers [if indicated], urinalysis, and TSH, T3 or FT3, and FT4 or equivalent) is performed within 72 hours 
of first dose of study treatment on Day 1, repeat testing is not required. 
i May be done within 24 hours prior to the visit. 
j For women of childbearing potential only. Serum pregnancy test must be performed within 72 hours of the first dose of study treatment (see Section 11.2.1). 
k Performed as described in Section 11.2.3. 
l If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other cycle thereafter. 
m Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only.  
n AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as described in Section 10.6.7, and any 
pregnancies that occur within 180 days post‑treatment are to be captured. 
o See Table 56 for details of TSR-042, TSR-022, and carboplatin-paclitaxel combination treatment administration in Part I. TSR-042 will be administered at a dose of 500 mg on 
Day 1 of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. TSR-022 will be 
administered at a dose of 900 mg on Day 1 Q3W for up to 2 years or or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 195 of 259 
Paclitaxel will be administered on Day 1 Q3W for 4 to 6 cycles as clinically indicated. Carboplatin will be administered on Day 1 every 3 weeks (Q3W) for 4 to 6 cycles as 
clinically indicated.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 196 of 259 
Table 34: 
Schedule of Events - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - Cycle 5 Through End of Study 
Cycle/Visit
a 
Cycle 
5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Up
b 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Serial tumor tissue biopsy (optional)
c 
 
 
 
X
d 
 
 
 
Blood sample for exploratory 
biomarkers 
 
X
e 
 
Xd 
 
 
 
Blood sample for PK and ADAs
f 
X 
X 
  
X
g 
Xg 
Xg 
 
Tumor assessment (RECIST v1.1)
h 
X 
 
X 
X
i 
Xi 
Xi 
Xi 
Laboratory assessments 
X
j 
Xj 
Xj 
X 
X
k 
Xk 
X 
CBC 
X 
X 
X 
X 
 
 
 
Serum chemistry 
X 
X 
X 
X 
X 
X 
 
Pregnancy test 
 
 
X
l 
 
Xk 
 
 
Serum tumor markers (if indicated) 
X 
 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
 
 
TSH, T3 or FT3, and FT4 
or equivalent
m 
 
Xl 
Xl 
X 
X 
 
 
ECGf 
 
 
 
X 
 
 
 
Physical examination 
 
 
 
X 
 
 
 
Symptom-directed physical 
examination 
X 
X 
X 
 
X 
 
 
Vital signs and weight
n 
X 
X 
X 
X 
X 
 
 
ECOG performance status 
X 
X 
X 
X 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
AE monitoring
o 
X 
X 
X 
X 
X 
X 
X 
TSR-042 study treatment administered
p 
X 
X 
X 
 
 
 
 
TSR-022 study treatment administeredp 
X 
X 
X 
 
 
 
 
Paclitaxel study treatment 
administeredp 
X 
X 
X 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 197 of 259 
 
Table 34: 
Schedule of Events - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - Cycle 5 Through End of Study 
(Continued) 
Cycle/Visit 
Cycle 
5 
Cycle 6 
Subsequent Cycles 
EOT 
Safety Follow-Up 
Survival 
Assessment 
(Every 
90 ± 14 Days)  
Day: 
Procedure 
1 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 Days 
Post-treatment 
90 ± 7 Days 
Post-treatment 
Carboplatin study treatment 
administeredp 
X 
X 
 
 
 
 
 
Survival assessment 
 
 
 
 
 
 
X 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AESI = adverse event of special interest; CBC = complete blood count; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FT3 = free triiodothyronine; FT4 = free thyroxine; EOT = end of treatment; PK = 
pharmacokinetics; Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1; SAE = serious 
adverse event; T3 = triiodothyronine; TSH = thyroid-stimulating hormone. 
a Treatment cycles are 21 days long, with visits on Day 1 of each cycle beyond Cycle 1, unless otherwise specified. Visits for subsequent cycles continue every 
21 days (±3 days) until study treatment discontinuation. 
b Safety follow-up visits are required only for those patients who have not started an alternate anticancer therapy as described in Section 11.2.5. 
c For patients who consent to optional serial biopsies, the biopsies will be obtained approximately 4 to 6 weeks after initiating study treatment and, whenever 
possible, at the time of disease progression (EOT visit) (note: while the biopsy is voluntary, it is highly encouraged). A core biopsy is recommended (details are 
provided in the Study Laboratory Manual). 
d Obtained at End of Treatment visit. EOT visit will occur within 7 days of study treatment discontinuation or at the time of disease progression, whichever 
occurs first. 
e Obtained predose. 
f PK and ADA blood sampling will be conducted on additional days during treatment cycles according to the cycle number and agent. Full details on PK and 
ADA blood sampling and ECG assessments are provided in Table 47 for Part I. 
g Blood sample for ADAs only. 
h Tumor assessment per RECIST v1.1 and appropriate testing of serum tumor markers will be performed as described in Section 11.2.3. Tumor assessments are 
to be performed within 1 week prior to Day 1 of Cycle 5. 
i Upon study treatment discontinuation, tumor assessment and appropriate testing of serum tumor markers will be performed as described in Section 11.2.4. If a 
patient discontinued treatment for a reason other than progression or death, withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals as described in Section 11.2.5 and Section 11.2.6 for the safety follow-up visits 
and survival assessment, respectively. 
j May be done within 24 hours prior to the visit. 
k Performed as described in Section 11.2.5. 
l Performed as described in Section 11.2.3. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 198 of 259 
m If TSH, T3 or FT3, or FT4 are not available, equivalent tests should be performed. TSH testing will be done at screening; Cycles 2, 4, and 6; and every other 
cycle thereafter. 
n Vital signs include blood pressure, pulse, and temperature. Height obtained at screening only. 
o AEs are required to be captured through 30 days after cessation of study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 days after 
cessation of study treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer therapy), AESIs are required to be captured as 
described in Section 10.6.7, and any pregnancies that occur within 180 days post‑treatment are to be captured. In conjunction with the survival assessment, 
AESIs (regardless of causality) and study-drug related SAEs will be collected every 90 ± 14 days after the last dose of study treatment. 
p See Table 56 for details of TSR-042, TSR-022, and carboplatin-paclitaxel combination treatment administration in Part I. TSR-042 will be administered at a 
dose of 500 mg on Day 1 of every cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, 
or death. TSR-022 will be administered at a dose of 900 mg on Day 1 Q3W for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. Paclitaxel will be administered on Day 1 Q3W for 4 to 6 cycles as clinically indicated. Carboplatin will be 
administered on Day 1 every 3 weeks (Q3W) for 4 to 6 cycles as clinically indicated. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 199 of 259 
Table 35: 
PK and ADA Blood Sampling and ECG Schedule - Part A - TSR-042 + Niraparib- Screening and Cycle 1 
Through Cycle 4 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 4 
Day 
-28 to -1 
1 
1 
2 
5 
8 
15 
1 
1 
2 
1 
2 
5 
8 
15 
Time Point/Assessment 
ECG 
ECG 
Blood 
ECG 
Blood 
Blood 
Anytime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-TSR-042 infusiona 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Post-TSR-042 infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
2 h (±30 min) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
24 h (±4 h) 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
96 h (±12 h) 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
168 h (±24 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
336 h (±24 h) 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
504 h (±24 h) 
 
 
 
 
 
 
 
 
Xb 
 
 
 
 
 
 
1008 h (±24 h) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-niraparib dosea 
 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
Post-niraparib dose 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 h (±15 min) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
2 h (±15 min) 
 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
4 h (±15 min) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
6 h (±30 min) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
8 h (±1 h) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
24 h (±2 h) 
 
 
 
Xc 
 
 
 
 
 
Xc 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; PK = pharmacokinetic.  
Note: All sampling times are relative to the start dosing of the specified study treatment. ECG should be conducted 30 minutes prior to PK blood draws for niraparib. 
a To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
b The 504-hour sample is the postdose sample from the prior cycle (Cycle 1) and the predose sample for this cycle (Cycle 2). It must be collected within 30 minutes of the dose 
given at this study visit. 
c The 24-hour sample is the postdose sample from the prior day (Day 1) and must be collected within 30 minutes of the dose given at this study visit (Day 2). 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 200 of 259 
Table 36: 
PK and ADA Blood Sampling and ECG Schedule - Part A - TSR-042 + Niraparib- Cycle 5 Through End of 
Treatment 
Cycle/Visit 
Cycle 5 
Cycle 
6 
Cycle 
7 
Cycle 11 
Cycle 
12 
Cycle 
13 
EOT 
Safety 
Follow-up 
(Post-treatment) 
Day 
1 
1 
2 
5 
8 
15 
1 
1 
1 
1 
2 
5 
8 
15 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 
Days  
90 ± 7 
Days 
Time Point/ 
Assessment 
ECG 
Blood 
Blood 
Blood 
ECG 
Blood 
Blood 
Blood 
ECG 
Blood 
Blood 
Blood 
Anytime 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Xa 
Xa 
Xa 
Pre-TSR-042 
infusionb 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Post-TSR-042 
infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
2 h (±30 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
24 h (±4 h) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
96 h (±12 h) 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
168 h (±24 h) 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
336 h (±24 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
504 h (±24 h)c 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
1008 h (±24 h)d 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Pre-niraparib doseb 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
Post-niraparib 
dose 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 h (±15 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic. Note: All sampling times are relative to the start dosing of 
the specified study treatment. ECG should be conducted 30 minutes prior to PK blood draws for niraparib.  
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
c The 504-hour sample is the postdose sample from the prior cycle (i.e., Cycle 5 or Cycle 11). It is collected during this cycle visit (i.e., Cycle 6 or Cycle 12).  
d The 1008-hour sample is the postdose sample from the prior dose (dose given on D1 Cycle 5 or D1 Cycle 11) and the predose sample from this cycle (i.e., Cycle 7 or Cycle 13). 
It must be collected within 30 minutes of the dose given at this study visit. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 201 of 259 
Table 37: 
PK and ADA Blood Sampling and ECG Schedule - Part B – TSR-042 + Carboplatin-Paclitaxel - Screening and 
Cycle 1 through Cycle 4 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 4 
Day 
-28 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
5 
8 
15 
Time Point/Assessment 
ECG 
Blood 
Blood 
Blood 
Anytime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-TSR-042 infusion
a 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Post-TSR-042 infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
2 h (±30 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
24 h (±4 h) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
96 h (±12 h) 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
168 h (±24 h) 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
336 h (±24 h) 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
504 h (±24 h) 
 
 
 
 
 
 
 
 
Xb 
 
 
 
 
 
Pre-carboplatin infusiona 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
Post-carboplatin infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min)c 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
1 h (±15 min)d 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
4 h (±15 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
6 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
8 h (±1 h) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
24 h (±2 h) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 202 of 259 
Table 37: 
PK and ADA Blood Sampling and ECG Schedule - Part B – TSR-042 + Carboplatin-Paclitaxel - Screening and 
Cycle 1 through Cycle 4 (Continued) 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 4 
Day 
-28 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
5 
8 
15 
Time Point/Assessment 
ECG 
Blood 
Blood 
Blood 
Pre-paclitaxel infusiona 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Post-paclitaxel infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.5 h (±15 min)c 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
3 h (±15 min)d 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
6 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
8 h (±1 h) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
24 h (±2 h) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
48 h (±4 h) 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
72 h (±8 h) 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
96 h (±12 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; PK = pharmacokinetic.  
Note: All sampling times are relative to the start dosing of the specified study treatment. 
a To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
b The 504-hour sample is the postdose sample from the prior cycle (Cycle 1) and the predose sample for this cycle (Cycle 2). It must be collected within 30 minutes of the dose 
given at this study visit. 
c Obtained during infusion of the specified study treatment. 
d Obtained at the end of infusion of the specified study treatment. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 203 of 259 
Table 38: 
PK and ADA Blood Sampling and ECG Schedule - Part B – TSR-042 + Carboplatin-Paclitaxel - Cycle 5 
Through End of Treatment 
Cycle/Visit 
Cycle 5 
Cycle 
6 
Cycle 
7 
Cycle 11 
Cycle 
12 
Cycle 
13 
EOT 
Safety Follow-up 
(Post-treatment) 
Day 
1 
2 
5 
8 
15 
1 
1 
1 
2 
5 
8 
15 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 
Days  
90 ± 7 
Days  
Time Point/Assessment 
Blood 
Blood 
Blood 
Blood 
Blood 
Blood 
ECG 
Blood 
Blood 
Blood 
Anytime 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Xa 
Xa 
Xa 
Pre-TSR-042 infusionb 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Post-TSR-042 infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
2 h (±30 min) 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
24 h (±4 h) 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
96 h (±12 h) 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
168 h (±24 h) 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
336 h (±24 h) 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
504 h (±24 h)c 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
1008 h (±24 h)d 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
Pre-carboplatin infusionb 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 h (±15 min)
f 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-paclitaxel infusionb  
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic. Note: All sampling times are relative to the start dosing of 
the specified study treatment. 
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
c The 504-hour sample is the postdose sample from the prior cycle (i.e., Cycle 5 or Cycle 11). It is collected during this cycle visit (i.e., Cycle 6 or Cycle 12).  
d The 1008-hour sample is the postdose sample from the prior dose (dose given on D1 Cycle 5 or D1 Cycle 11) and the predose sample from this cycle (i.e., Cycle 7 or Cycle 13). 
It must be collected within 30 minutes of the dose given at this study visit. 
e Collect only if there is dose of paclitaxel and carboplatin for Cycle 5. 
f Obtained at the end of infusion of the specified study treatment.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 204 of 259 
Table 39: 
PK and ADA Blood Sampling and ECG Schedule - Part C - TSR-042 + Niraparib + Bevacizumab - Screening 
and Cycle 1 Through Cycle 4 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 4 
Day 
-28 to -1 
1 
1 
2 
5 
8 
15 
1 
1 
2 
1 
2 
5 
8 
15 
Time Point/Assessment 
ECG 
ECG 
Blood 
ECG 
Blood 
Blood 
Anytime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-TSR-042 infusiona 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Post-TSR-042 infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
2 h (±30 min) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
24 h (±4 h) 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
96 h (±12 h) 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
168 h (±24 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
336 h (±24 h) 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
504 h (±24 h) 
 
 
 
 
 
 
 
 
Xb 
 
 
 
 
 
 
1008 h (±24 h) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-niraparib dosea 
 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
Post-niraparib dose 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 h (±15 min) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
2 h (±15 min) 
 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
4 h (±15 min) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
6 h (±30 min) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
8 h (±1 h) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
24 h (±2 h) 
 
 
 
Xc 
 
 
 
 
 
Xc 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; PK = pharmacokinetic. 
Note: All sampling times are relative to the start dosing of the specified study treatment. ECG should be conducted 30 minutes prior to PK blood draws for niraparib. 
a To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
b The 504-hour sample is the postdose sample from the prior cycle (Cycle 1) and the predose sample for this cycle (Cycle 2). It must be collected within 30 minutes of the dose 
given at this study visit. 
c The 24-hour sample is the postdose sample from the prior day (Day 1) and must be collected within 30 minutes of the dose given at this study visit (Day 2). 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 205 of 259 
Table 40: 
PK and ADA Blood Sampling and ECG Schedule - Part C - TSR-042 + Niraparib + Bevacizumab - Cycle 5 
Through End of Treatment 
Cycle/Visit 
Cycle 5 
Cycle 
6 
Cycle 
7 
Cycle 11 
Cycle 
12 
Cycle 
13 
EOT 
Safety 
Follow-up 
(Post-treatment) 
Day 
1 
1 
2 
5 
8 
15 
1 
1 
1 
1 
2 
5 
8 
15 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 
Days  
90 ± 7 
Days 
Time Point/ 
Assessment 
ECG 
Blood 
Blood 
Blood 
ECG 
Blood 
Blood 
Blood 
ECG 
Blood 
Blood 
Blood 
Anytime 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Xa 
Xa 
Xa 
Pre-TSR-042 
infusionb 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Post-TSR-042 
infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
2 h (±30 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
24 h (±4 h) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
96 h (±12 h) 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
168 h (±24 h) 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
336 h (±24 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
504 h (±24 h)c 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
1008 h (±24 h)d 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Pre-niraparib 
doseb 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
Post-niraparib 
dose 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 h (±15 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic. Note: All sampling times are relative to the start dosing of 
the specified study treatment. ECG should be conducted 30 minutes prior to PK blood draws for niraparib. 
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
c The 504-hour sample is the postdose sample from the prior cycle (i.e., Cycle 5 or Cycle 11). It is collected during this cycle visit (i.e., Cycle 6 or Cycle 12). 
d The 1008-hour sample is the postdose sample from the prior dose (dose given on D1 Cycle 5 or D1 Cycle 11) and the predose sample from this cycle (i.e., Cycle 7 or Cycle 13). 
It must be collected within 30 minutes of the dose given at this study visit.  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 206 of 259 
Table 41: 
PK and ADA Blood Sampling and ECG Schedule - Part D – TSR-042 + Carboplatin-Paclitaxel + Bevacizumab - 
Screening and Cycle 1 through Cycle 4 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 4 
Day 
-28 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
5 
8 
15 
Time Point/Assessment 
ECG 
Blood 
Blood 
Blood 
Anytime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-TSR-042 infusiona 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Post-TSR-042 infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
2 h (±30 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
24 h (±4 h) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
96 h (±12 h) 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
168 h (±24 h) 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
336 h (±24 h) 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
504 h (±24 h) 
 
 
 
 
 
 
 
 
X
b 
 
 
 
 
 
Pre-carboplatin infusiona 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
Post-carboplatin infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min)c 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
1 h (±15 min)d 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
4 h (±15 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
6 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
8 h (±1 h) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
24 h (±2 h) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 207 of 259 
Table 41: 
PK and ADA Blood Sampling and ECG Schedule - Part D – TSR-042 + Carboplatin-Paclitaxel + Bevacizumab - 
Screening and Cycle 1 through Cycle 4 (Continued) 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 4 
Day 
-28 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
5 
8 
15 
Time Point/Assessment 
ECG 
Blood 
Blood 
Blood 
Pre-paclitaxel infusiona 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Post-paclitaxel infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.5 h (±15 min)c 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
3 h (±15 min)d 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
6 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
8 h (±1 h) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
24 h (±2 h) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
48 h (±4 h) 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
72 h (±8 h) 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
96 h (±12 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; PK = pharmacokinetic. 
Note: All sampling times are relative to the start dosing of the specified study treatment. 
a To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
b The 504-hour sample is the postdose sample from the prior cycle (Cycle 1) and the predose sample for this cycle (Cycle 2). It must be collected within 30 minutes of the dose 
given at this study visit. 
c Obtained during infusion of the specified study treatment. 
d Obtained at the end of infusion of the specified study treatment. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 208 of 259 
Table 42: 
PK and ADA Blood Sampling and ECG Schedule - Part D – TSR-042 + Carboplatin-Paclitaxel + Bevacizumab - 
Cycle 5 Through End of Treatment 
Cycle/Visit 
Cycle 5 
Cycle 
6 
Cycle 
7 
Cycle 11 
Cycle 
12 
Cycle 
13 
EOT 
Safety Follow-up 
(Post-treatment) 
Day 
1 
2 
5 
8 
15 
1 
1 
1 
2 
5 
8 
15 
1 
1 
+7 Days 
Post-treatment 
30 ± 7 
Days  
90 ± 7 
Days  
Time Point/Assessment 
Blood 
Blood 
Blood 
Blood 
Blood 
Blood 
ECG 
Blood 
Blood 
Blood 
Anytime 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Xa 
Xa 
Xa 
Pre-TSR-042 infusionb 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Post-TSR-042 infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min) 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
2 h (±30 min) 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
24 h (±4 h) 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
96 h (±12 h) 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
168 h (±24 h) 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
336 h (±24 h) 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
504 h (±24 h)c 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
1008 h (±24 h)d 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
Pre-carboplatin 
infusionb 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 h (±15 min)f 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-paclitaxel infusionb 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic. Note: All sampling times are relative to the start dosing of 
the specified study treatment.  
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to the administration of the dose of the corresponding agent for the cycle. 
c The 504-hour sample is the postdose sample from the prior cycle (i.e., Cycle 5 or Cycle 11). It is collected during this cycle visit (i.e., Cycle 6 or Cycle 12).   
d The 1008-hour sample is the postdose sample from the prior dose (dose given on D1 Cycle 5 or D1 Cycle 11) and the predose sample from this cycle (i.e., Cycle 7 or Cycle 13). 
It must be collected within 30 minutes of the dose given at this study visit. 
e Collect only if there is dose of paclitaxel and carboplatin for Cycle 5. 
f Obtained at the end of infusion of the specified study treatment. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 209 of 259 
Table 43: 
PK and ADA Blood Sampling and ECG Schedule - Part E – TSR-042 + Carboplatin-Pemetrexed - Screening 
and Treatment Cycles 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 5 
EOT 
Safety 
follow-up 
(Post-
treatment) 
Day 
-21 to -1 
1 
2 
3 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 
7 days post-
treatment 
30 ± 7 
Days  
90 ± 7 
Days  
Time 
Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG 
Blood Blood 
Blood 
Anytime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Xa 
Xa 
Xa 
Pre-TSR-042 
infusionb 
 
X 
 
 
 
 
 
X 
X 
 
 
 
 
 
  
  
  
 
Post-TSR-042 
infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
0.5 h (±5 min)c 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
  
  
  
 
2 h (±30 min) 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
  
  
  
 
24 h (±4 h) 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
  
  
  
 
48 h (±4 h) 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
  
  
  
 
96 h (±12 h) 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
  
  
  
 
168 h (±24 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
  
  
  
 
336 h (±24 h) 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
  
  
  
 
Pre-pemetrexed 
infusionb 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
  
  
  
 
Post-pemetrexed 
infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
10 min (±2 min)c 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
  
  
  
 
0.5 h (±5 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
1 h (±15 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
4 h (±15 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
6 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
8 h (±1 h) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
24 h (±2 h) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 210 of 259 
Table 43: 
PK and ADA Blood Sampling and ECG Schedule - Part E – TSR-042 + Carboplatin-Pemetrexed - Screening 
and Treatment Cycles (Continued) 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 2 
Cycle 5 
EOT 
Safety 
follow-up 
(Post-
treatment) 
Day 
-21 to -1 
1 
2 
3 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 
7 days post-
treatment 
30 ± 7 
Days  
90 ± 7 
Days  
Time 
Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG 
Blood Blood 
Blood 
Pre-carboplatin 
infusionb 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
  
  
  
 
Post-carboplatin 
infusion 
  
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
0.5 h (±5 min)d 
  
X 
  
 
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
1 h (±15 min)e 
  
X 
  
 
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
4 h (±15 min) 
  
X 
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
6 h (±30 min) 
  
X 
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
8 h (±1 h) 
  
X 
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
24 h (±2 h) 
  
  
X 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic. 
Infusion order: 1) TSR-042 30 min; 2) pemetrexed 10 min; 3) carboplatin 30 min or 60 min 
Note: All sampling times are relative to the start dosing of the specified study treatment. 
Note: PK assessments will be performed for TSR-042, carboplatin, and pemetrexed. ADA assessments will be performed for TSR-042.  
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to administration of the specified study treatment. 
c Obtained at the end of infusion of the specified study treatment. 
d For carboplatin, 0.5 h sample is collected during the infusion for 1 h insert and the end of infusion for 0.5 h insert. 
e For carboplatin, 1 h sample is collected at the end of infusion for 1 h insert and as the postdose 1 h sample for 0.5 h insert. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 211 of 259 
Table 44: 
PK and ADA Blood Sampling and ECG Schedule - Part F – TSR-042 + TSR-022 + Carboplatin-Pemetrexed - 
Screening and Treatment Cycles 
Cycle/Visit 
Screening 
Cycle 1 
Cycl
e 2 
Cycle 5 
EOT 
Safety 
follow-up  
(Post 
treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 7 days post-
treatment 
30±7 
Days  
90±7 
Days  
Time 
Point/Assessment 
ECG 
Blood 
Bloo
d 
Blood 
EC
G 
Blood Blood Bloo
d 
Anytime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Xa 
Xa 
Xa 
Pre-TSR-042 and 
TSR-022 infusionb 
 
X 
 
 
 
 
 
 
X 
X 
  
  
  
  
  
  
  
  
 
Post-TSR-042 
infusion
c 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
0.5 h (±5 min)d 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
  
  
  
 
1 h (±15 min)e 
 
X 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
  
  
 
2 h (±30 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
  
  
  
 
3 h (±30 min) 
 
X 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
  
  
 
24 h (±4 h) 
 
  
X 
  
 
 
 
 
 
  
X 
  
  
  
  
  
  
  
 
48 h (±4 h) 
 
  
  
X 
 
 
 
 
 
  
  
X 
  
  
  
  
  
  
 
96 h (±12 h) 
 
  
  
  
 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
 
168 h (±24 h) 
 
  
  
  
 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
 
336 h (±24 h) 
 
  
  
  
 
  
  
X 
  
  
  
  
  
  
X 
  
  
  
 
Pre-pemetrexed 
infusionb 
 
X 
  
  
 
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
Post-pemetrexed 
infusion 
 
  
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
10 min (±2 min)f 
 
X 
  
  
 
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
0.5 h (±5 min) 
 
X 
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
1 h (±15 min) 
 
X 
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
4 h (±15 min) 
 
X 
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
6 h (±30 min) 
 
X 
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
8 h (±1 h) 
 
X 
  
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
24 h (±2 h) 
 
  
X 
  
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 212 of 259 
Table 44: 
PK and ADA Blood Sampling and ECG Schedule - Part F – TSR-042 + TSR-022 + Carboplatin-Pemetrexed - 
Screening and Treatment Cycles (Continued) 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 
2 
Cycle 5 
EOT 
Safety follow-
up  
(Post-
treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 7 days post-
treatment 
30±7 
Days  
90±7 
Days  
Time 
Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG Blood Blood Blood 
Pre-carboplatin 
infusionb 
  
X 
  
  
  
  
  
  
X 
 
  
  
  
  
  
  
 
Post-carboplatin 
infusion 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
0.5 h (±5 min)g 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
1 h (±15 min)h 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
4 h (±15 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
6 h (±30 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
8 h (±1 h) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
24 h (±2 h) 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic. 
Infusion order: 1) TSR-042 30 min; 2) TSR-022 30 min; 3) pemetrexed 10 min; 4) carboplatin 30 or 60 min. 
Note: All sampling times are relative to the start dosing of the specified study treatment. 
Note: PK assessments will be performed for TSR-042, TSR-022, carboplatin, and pemetrexed. ADA assessments will be performed for TSR-042 and TSR-022.  
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to administration of the specified study treatment. For both TSR-042 and TSR-022, it is obtained within 30 min prior to the 
administration of TSR-042. 
c Samplings for both TSR-042 and TSR-022 use the same schedule and are relative to the start infusion of TSR-042. 
d End of infusion for TSR-042. 
e End of infusion for TSR-022. 
f End of infusion for pemetrexed. 
g For carboplatin, 0.5 h sample is collected during the infusion for 1 h insert and the end of infusion for 0.5 h insert. 
h For carboplatin, 1 h sample is collected at the end of infusion for 1 h insert and as the postdose 1 h sample for 0.5 h insert. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 213 of 259 
Table 45: 
PK and ADA Blood Sampling and ECG Schedule - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - Screening 
and Treatment Cycles 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 
2 
Cycle 5 
EOT 
Safety 
follow-up 
(Post-
treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 
7 days post-
treatment 
30±7 
days  
90±7 
days  
Time Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG Bloo
d 
Blood Blood 
Anytime 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Xa 
X
a 
Xa 
Pre-TSR-042 infusionb 
  
X 
  
  
  
  
  
  
X 
X 
  
  
  
  
  
  
  
  
 
Post-TSR-042 infusion 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
0.5 h (±5 min)c 
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
 
2 h (±30 min) 
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
 
24 h (±4 h) 
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
 
48 h (±4 h) 
  
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
 
96 h (±12 h) 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
 
168 h (±24 h) 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
 
336 h (±24 h) 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
  
  
 
Pre-nab-paclitaxel 
infusionb 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
Post-nab-paclitaxel 
infusion 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
30 min (±2 min)c 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
1.0 h (±5 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
1.5 h (±15 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
3 h (±15 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
6 h (±30 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
8 h (±1 h) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
24 h (±2 h) 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
48 h (±4 h) 
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
72 h (±8 h) 
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
96 h (±12 h) 
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 214 of 259 
Table 45: 
PK and ADA Blood Sampling and ECG Schedule - Part G – TSR-042 + Carboplatin–Nab-Paclitaxel - Screening 
and Treatment Cycles (Continued) 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 
2 
Cycle 5 
EOT 
Safety follow-
up (Post 
treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 
7 days post-
treatment 
30±7 
days  
90±7 
days  
Time Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG Blood Blood Blood 
Pre-carboplatin infusionb 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
 
Post-carboplatin infusion 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
0.5 h (±5 min)d 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
1 h (±15 min)e 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
4 h (±15 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
6 h (±30 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
8 h (±1 h) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
24 h (±2 h) 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic.  
Infusion order: 1) TSR-042 30 min; 2) nab-paclitaxel 30 min; 3) carboplatin 30 min or 60 min. 
Note: All sampling times are relative to the start dosing of the specified study treatment. 
Note: PK assessments will be performed for TSR-042, carboplatin, and nab-paclitaxel. ADA assessments will be performed for TSR-042.  
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to administration of the specified study treatment. 
c Obtained at the end of infusion of the specified study treatment. 
d For carboplatin, 0.5 h sample is collected during the infusion for 1 h insert and the end of infusion for 0.5 h insert. 
e For carboplatin, 1 h sample is collected at the end of infusion for 1 h insert and as the postdose 1 h sample for 0.5 h insert. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 215 of 259 
Table 46: 
PK and ADA Blood Sampling and ECG Schedule - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-Paclitaxel 
- Screening and Treatment Cycles 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 
2 
Cycle 5 
EOT 
Safety follow-up 
(Post treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 
7 days post-
treatment 
30±7 days 
90±7 days 
Time 
Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG 
Blood 
Blood 
Blood 
Anytime 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Xa 
X
a 
X
a 
Pre-TSR-042 and 
TSR-022 infusion
b 
  
X 
  
  
  
  
  
  
X 
X 
  
  
  
  
  
  
  
  
 
Post-TSR-042 
infusion
c 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
0.5 h (±5 min)
d 
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
 
1 h (±15 min)
e 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
2 h (±30 min) 
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
 
3 h (±30 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
24 h (±4 h) 
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
 
48 h (±4 h) 
  
  
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
 
96 h (±12 h) 
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
 
168 h (±24 h) 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
 
336 h (±24 h) 
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
X   
  
  
 
Pre-nab-paclitaxel 
infusionb 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
Post-nab-paclitaxel 
infusion 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
30 min (±2 min)f 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
1.0 h (±5 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
1.5 h (±15 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
3 h (±15 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
6 h (±30 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
8 h (±1 h) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
24 h (±2 h) 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
48 h (±4 h) 
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
72 h (±8 h) 
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 216 of 259 
Table 46: 
PK and ADA Blood Sampling and ECG Schedule - Part H – TSR-042 + TSR-022 + Carboplatin–Nab-Paclitaxel 
- Screening and Treatment Cycles (Continued) 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 
2 
Cycle 5 
EOT 
Safety follow-
up  
(Post 
treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 7 days post-
treatment 
30±7 
days  
90±7 
days  
Time 
Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG Blood Blood Blood 
96 h (±12 h) 
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
 
Pre-carboplatin 
infusionb 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
Post-carboplatin 
infusion 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
0.5 h (±5 min)
g 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
1 h (±15 min)
h 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
4 h (±15 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
6 h (±30 min) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
8 h (±1 h) 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
24 h (±2 h) 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic.  
Infusion order: 1) TSR-042 30 min; 2) TSR-022 30 min; 3) nab-paclitaxel 30 min; 4) carboplatin 30 or 60 min. 
Note: All sampling times are relative to the start dosing of the specified study treatment. 
Note: PK assessments will be performed for TSR-042, TSR-022, carboplatin, and nab-paclitaxel. ADA assessments will be performed for TSR-042 and TSR-022.  
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to administration of the specified study treatment. For both TSR-042 and TSR-022, it is obtained within 30 min prior to the 
administration of TSR-042. 
c Samplings for both TSR-042 and TSR-022 use the same schedule and are relative to the start infusion of TSR-042. 
d End of infusion for TSR-042. 
e End of infusion for TSR-022. 
f End of infusion for nab-paclitaxel. 
g For carboplatin, 0.5 h sample is collected during the infusion for 1 h insert and the end of infusion for 0.5 h insert. 
h For carboplatin, 1 h sample is collected at the end of infusion for 1 h insert and as the postdose 1 h sample for 0.5 h insert. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 217 of 259 
Table 47: 
PK and ADA Blood Sampling and ECG Schedule - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - 
Screening and Treatment Cycles 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 
2 
Cycle 5 
EOT 
Safety follow-
up (Post 
treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 7 days post-
treatment 
30±7 
days  
90±7 
days  
Time Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG Blood Blood Blood 
Anytime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Xa 
Xa 
X
a 
Pre-TSR-042 and TSR-
022 infusionb 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
Post-TSR-042 infusionc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min)d 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
1 h (±15 min)
e 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 h (±30 min) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
3 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24 h (±4 h) 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
48 h (±4 h) 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
96 h (±12 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
168 h (±24 h) 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
336 h (±24 h) 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Pre-paclitaxel infusionb  
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Post-paclitaxel infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.5 h (±15 min)f 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 h (±15 min)g 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 h (±1 h) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24 h (±2 h) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
48 h (±4 h) 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
72 h (±8 h) 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
96 h (±12 h) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 218 of 259 
Table 47: 
PK and ADA Blood Sampling and ECG Schedule - Part I – TSR-042 + TSR-022 + Carboplatin-Paclitaxel - 
Screening and Treatment Cycles (Continued) 
Cycle/Visit 
Screening 
Cycle 1 
Cycle 
2 
Cycle 5 
EOT 
Safety 
follow-up 
(Post 
treatment) 
Day 
-21 to -1 
1 
2 
3 
4 
5 
8 
15 
1 
1 
2 
3 
5 
8 
15 
7 days post-
treatment 
30±7 
days 
90±7 
days 
Time 
Point/Assessment 
ECG 
Blood 
Blood 
Blood 
ECG Blood Blood Blood 
Pre-carboplatin 
infusionb 
wp 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Post-carboplatin 
infusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0.5 h (±5 min)h 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
1 h (±15 min)i 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
4 h (±15 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 h (±30 min) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 h (±1 h) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24 h (±2 h) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOT = end of treatment; PK = pharmacokinetic.  
Infusion order: 1) TSR-042 30 min; 2) TSR-022 30 min; 3) paclitaxel 3 hours; 4) carboplatin 30 or 60 min. 
Note: All sampling times are relative to the start dosing of the specified study treatment. 
Note: PK assessments will be performed for TSR-042, TSR-022, carboplatin, and paclitaxel. ADA assessments will be performed for TSR-042 and TSR-022.  
a Sample collected for TSR-042 ADA assessment only. 
b To be obtained within 30 minutes prior to administration of the specified study treatment. For both TSR-042 and TSR-022, it is obtained within 30 min prior to the 
administration of TSR-042. 
c Samplings for both TSR-042 and TSR-022 use the same schedule and are relative to the start infusion of TSR-042. 
d End of infusion for TSR-042. 
e End of infusion for TSR-022. 
f During the infusion of paclitaxel. 
g End of infusion of paclitaxel. 
h For carboplatin, 0.5 h sample is collected during the infusion for 1 h insert and the end of infusion for 0.5 h insert. 
i For carboplatin, 1 h sample is collected at the end of infusion for 1 h insert and as the postdose 1 h sample for 0.5 h insert. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 219 of 259 
Table 48: 
TSR-042 and Niraparib Combination Treatment Administration and Dispensation/Collection - Part A 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
Niraparib 200 mg PO on Days 1 to 21 Q3W (dose level 1)
a,b,c 
X 
X 
X 
X 
X 
X 
X 
Niraparib 300 mg PO on Days 1 to 21 Q3W (dose level 2)a,c 
X 
X 
X 
X 
X 
X 
X 
TSR-042 IV on Day 1 Q3W for 4 cycles, then Day 1 Q6W 
Xd 
Xd 
Xd 
Xd 
X
e 
 
Xe 
Abbreviations: IV = intravenous; PO = oral; Q3W = every 3 weeks; Q6W = every 6 weeks; QD = once daily.  
a On Day 1 of each cycle conducted at the study site, the niraparib dose will be administered upon completion of TSR-042 infusion. After the Day 1 visit, patients will continue to 
take niraparib each day of every cycle thereafter (i.e., on Days 1 to 21) until treatment discontinuation. 
b The dose of niraparib may be increased after Cycle 2 to a higher dose level that has been found to be safe during the dose-escalation phase following discussion with the 
Sponsor. Otherwise, niraparib will continue to be administered during each cycle at the same regimen as in Cycle 1. 
c Niraparib will be dispensed/collected on Day 1 of every 21-day cycle (Q3W). 
d TSR-042 administered at the study site IV at 500 mg on Day 1 of every 3-week cycle (Q3W) for 4 cycles. 
e TSR-042 administered at the study site IV at 1,000 mg on Day 1 of every other cycle (Q6W) for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, 
Investigator’s decision, or death. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 220 of 259 
Table 49: 
TSR-042 and Carboplatin-Paclitaxel Combination Treatment Administration - Part B 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
Carboplatin AUC of 5 or 6 IV on Day 1
a,b,c 
X 
X 
X 
X 
X 
X 
 
Paclitaxel 175 mg/m2 IV on Day 1b,c 
X 
X 
X 
X 
X 
X 
 
TSR-042 on Day 1 Q3W for 4 cycles, then Day 1 Q6Wb 
X
d 
Xd 
Xd 
Xd 
X
e 
 
Xe 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. 
b The TSR-042 infusion is administered first, followed by the paclitaxel infusion and the carboplatin infusion. 
c Carboplatin and paclitaxel will be administered for 4 to 6 cycles as clinically indicated. 
d TSR-042 administered at the study site IV at 500 mg on Day 1 of every 3-week cycle (Q3W) for 4 cycles. 
e TSR-042 administered at the study site IV at 1,000 mg on Day 1 of every other cycle (Q6W) for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, 
Investigator’s decision, or death. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 221 of 259 
Table 50: 
TSR-042, Niraparib, and Bevacizumab Combination Treatment Administration and Dispensation/Collection- 
Part C 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
Niraparib 200 mg PO on Days 1 to 21 Q3W (dose level 1)
a,b,c 
X 
X 
X 
X 
X 
X 
X 
Niraparib 300 mg PO on Days 1 to 21 Q3W (dose level 2)a,c 
X 
X 
X 
X 
X 
X 
X 
TSR-042 IV on Day 1 Q3W for 4 cycles, then Day 1 Q6W 
X
d 
Xd 
Xd 
Xd 
X
e 
 
Xe 
Bevacizumab IV on Day 1 Q3W for up to 15 months
f 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: IV = intravenous; PO = oral; Q3W = every 3 weeks; Q6W = every 6 weeks; QD = once daily. 
a On Day 1 of each cycle conducted at the study site, the niraparib dose will be administered upon completion of TSR-042 infusion. After the Day 1 visit, patients will continue to 
take niraparib each day of every cycle thereafter (i.e., on Days 1 to 21) until treatment discontinuation. 
b The dose of niraparib may be increased after Cycle 2 to a higher dose level that has been found to be safe during the dose-escalation phase following discussion with the 
Sponsor. Otherwise, niraparib will continue to be administered during each cycle at the same regimen as in Cycle 1. 
c Niraparib will be dispensed/collected on Day 1 of every 21-day cycle (Q3W). 
d TSR-042 administered at the study site IV at 500 mg on Day 1 of every 3-week cycle (Q3W) for 4 cycles. 
e TSR-042 administered at the study site IV at 1,000 mg on Day 1 of every other cycle (Q6W) for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, 
Investigator’s decision, or death. 
f Bevacizumab administered at the study site IV at 15mg/kg on Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 222 of 259 
Table 51: 
TSR-042, Carboplatin-Paclitaxel, and Bevacizumab Combination Treatment Administration - Part D 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
Carboplatin AUC of 5 or 6 IV on Day 1a,b,c 
X 
X 
X 
X 
X 
X 
 
Paclitaxel 175 mg/m2 IV on Day 1b,c 
X 
X 
X 
X 
X 
X 
 
TSR-042 on Day 1 Q3W for 4 cycles, then Day 1 Q6Wb 
Xd 
Xd 
Xd 
Xd 
Xe 
 
Xe 
Bevacizumab IV on Day 1 Q3W for up to 15 months
f 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; Q3W = every 3 weeks; Q6W = every 6 weeks. 
a The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. 
b The TSR-042 infusion is administered first, followed by the paclitaxel infusion, the carboplatin infusion, and lastly the bevacizumab infusion. 
c Carboplatin and paclitaxel will be administered for 4 to 6 cycles as clinically indicated. 
d TSR-042 administered at the study site IV at 500 mg on Day 1 of every 3-week cycle (Q3W) for 4 cycles. 
e TSR-042 administered at the study site IV at 1,000 mg on Day 1 of every other cycle (Q6W) until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s 
decision, or death. 
f Bevacizumab administered at the study site IV at 15mg/kg on Day 1 of every 21-day cycle (Q3W) for up to 15 months. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 223 of 259 
Table 52: 
TSR-042 and Carboplatin-Pemetrexed Combination Treatment Administration - Part E 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
TSR-042 on Day 1 Q3Wa 
X 
X 
X 
X 
X 
X 
X 
Pemetrexed 500 mg/m2 IV on Day 1 Q3W
b 
X 
X 
X 
X 
X 
X 
X 
Carboplatin AUC of 5 or 6 IV on Day 1 Q3W
c 
X 
X 
X 
X 
X 
X 
 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; Q3W = every 3 weeks. 
Infusion order: 1) TSR-042 30 min; 2) pemetrexed 10 min; 3) carboplatin 30 or 60 min. 
a TSR-042 will be administered at the study site IV at 500 mg on Day 1 of every 21-day cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. 
b Pemetrexed 500 mg/m2 will be administered by IV infusion over 10 minutes Q3W for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, Investigator’s 
decision, or death. All patients should receive the appropriate supplementation of vitamin B12, folic acid, and corticosteroid prophylaxis. 
c The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. Carboplatin 
will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 224 of 259 
Table 53: 
TSR-042, TSR-022, and Carboplatin-Pemetrexed Combination Treatment Administration - Part F 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent 
Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
TSR-042 on Day 1 Q3Wa 
X 
X 
X 
X 
X 
X 
X 
TSR-022 on Day 1 Q3Wb 
 X 
 X 
 X 
 X 
X 
X 
X 
Pemetrexed 500 mg/m2 IV on Day 1 Q3W
c 
X 
X 
X 
X 
X 
X 
X 
Carboplatin AUC of 5 or 6 IV on Day 1 Q3Wd 
X 
X 
X 
X 
X 
X  
 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; Q3W = every 3 weeks. 
Infusion order: 1) TSR-042 30 min; TSR-022 30 min; 3) pemetrexed 10 min; 4) carboplatin 30 or 60 min. 
a TSR-042 will be administered at the study site IV at 500 mg on Day 1 of every 21-day cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. 
b TSR-022 will be administered at the study site IV at 900 mg on Day 1 of every 21-day cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. A dose of 900 mg of TSR-022 has been found to be the highest safest dose that provides maximal pharmacodynamic effect; this 
dose may be lowered to dose level -1 if needed. Based on available safety information, the Sponsor may decide to test additional dose levels of TSR-022. 
c Pemetrexed 500 mg/m2 will be administered by IV infusion over 10 minutes Q3W. All patients should receive the appropriate supplementation of vitamin B12, folic acid, and 
corticosteroid prophylaxis for up to 2 years or until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s decision, or death. 
d The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. Carboplatin 
will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 225 of 259 
Table 54: 
TSR-042 and Carboplatin–Nab-Paclitaxel Combination Treatment Administration - Part G 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
TSR-042 on Day 1 Q3Wa 
X 
X 
X 
X 
X 
X 
X 
Nab-paclitaxel 100 mg/m2 IV on Day 1 Q1W
b 
X 
X 
X 
X 
X 
X 
X 
Carboplatin AUC of 5 or 6 IV on Day 1 Q3W
c 
X 
X 
X 
X 
X 
X 
 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; Q3W = every 3 weeks. 
Infusion order: 1) TSR-042 30 min; 2) nab-paclitaxel 30 min; 3) carboplatin 30 or 60 min. 
a TSR-042 will be administered at the study site IV at 500 mg on Day 1 of every 21-day cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. 
b Nab-paclitaxel 100 mg/m2 will be administered by IV infusion over 30 minutes on Days 1, 8, and 15 (Q1W) of every 3-week cycle for 4 to 6 cycles as clinically indicated.  
c The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. Carboplatin 
will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 226 of 259 
Table 55: 
TSR-042, TSR-022, and Carboplatin–Nab-Paclitaxel Combination Treatment Administration - Part H 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent 
Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
TSR-042 on Day 1 Q3Wa 
X 
X 
X 
X 
X 
X 
X 
TSR-022 on Day 1 Q3Wb 
 X 
 X 
 X 
 X 
X 
X 
X 
Nab-paclitaxel 100 mg/m2 IV on Day 1 Q1W
c 
X 
X 
X 
X 
X 
X 
X 
Carboplatin AUC of 5 or 6 IV on Day 1 Q3W
d 
X 
X 
X 
X 
X 
X 
 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; Q1W = every week; Q3W = every 3 weeks. 
Infusion order: 1) TSR-042 30 min; TSR-022 30 min; 3) nab-paclitaxel 30 min; 4) carboplatin 30 or 60 min. 
a TSR-042 will be administered at the study site IV at 500 mg on Day 1 of every 21-day cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death or until treatment discontinuation. 
b TSR-022 will be administered at the study site IV at 900 mg on Day 1 of every 21-day cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides maximal 
pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available safety information, the Sponsor may decide to test additional dose levels of 
TSR-022. 
c Nab-paclitaxel 100 mg/m2 will be administered by IV infusion over 30 minutes Q1W on Days 1, 8, and 15 (Q1W) of every 3-week cycle for 4 to 6 cycles as clinically indicated.  
d The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. Carboplatin 
will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 227 of 259 
Table 56: 
TSR-042, TSR-022, and Carboplatin-Paclitaxel Combination Treatment Administration - Part I 
Cycle/Visit 
1 
2 
3 
4 
5 
6 
Subsequent 
Cycles 
Day 
1 
1 
1 
1 
1 
1 
1 
TSR-042 on Day 1 Q3Wa 
X 
X 
X 
X 
X 
X 
X 
TSR-022 on Day 1 Q3Wb 
 X 
 X 
 X 
 X 
X 
X 
X 
Paclitaxel 175 mg/m2 IV on Day 1 Q3W
c 
X 
X 
X 
X 
X 
X 
X 
Carboplatin AUC of 5 or 6 IV on Day 1 Q3W
d 
X 
X 
X 
X 
X 
X 
 
Abbreviations: AUC = area under the plasma or serum concentration-time curve; IV = intravenous; Q3W = every 3 weeks. 
Infusion order: 1) TSR-042 30 min; 2) TSR-022 30 min; 3) paclitaxel 3 hours; 4) carboplatin 30 or 60 min. 
a TSR-042 will be administered at the study site IV at 500 mg on Day 1 of every 3 weeks (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. 
b TSR-022 will be administered at the study site IV at 900 mg on Day 1 of every 21-day cycle (Q3W) for up to 2 years or until disease progression, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death. 900 mg of TSR-022 is the highest dose tested in dose escalation in combination with TSR-042 that provides maximal 
pharmacodynamic effect; this dose may be lowered to dose level -1 if needed. Based on available safety information, the Sponsor may decide to test additional dose levels of 
TSR-022. 
c Paclitaxel 175 mg/m2 will be administered by IV infusion over 3 hours Q3W for 4 to 6 cycles as clinically indicated.  
d The carboplatin dose will be determined by the Investigator, taking into consideration the patient’s prior anticancer therapies and pre-existing medical conditions. Carboplatin 
will be administered on Day 1 of every 21-day cycle (Q3W) for 4 to 6 cycles as clinically indicated. 
 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 228 of 259 
11.2. 
Procedures by Visit 
11.2.1. 
Screening Visit 
Standard of care tests or procedures, including radiographic scans, laboratory assessments 
(fasting glucose at baseline), ECG, physical examination, vital signs, height, and weight, 
performed prior to the patient signing the ICF can be used as part of the screening assessments as 
long as the tests or procedures meet the protocol-required timelines (i.e., within 28 days of first 
dose for these procedures with the exception of pregnancy testing, which must be conducted 
within 72 hours of first dose) and any relevant guidelines (e.g., diagnostic quality for 
radiographic scans). Note that source documents must clearly identify the standard of care tests 
or procedures that are used for screening, and the results of these tests or procedures must be 
entered in the eCRF. 
At screening, the following procedures/tests will be performed: 
 Obtain written informed consent 
 A single study ICF will be signed before any study procedures. 
 Inclusion/exclusion criteria review 
 Demographics 
 Medical/surgical/cancer/medication history 
 For patients in Parts A, B, C, D, E, and G:  
 Optional collection of archival FFPE tumor tissue sample (if available) for 
biomarker testing 
 For patients in Parts F, H, and I: 
 Mandatory collection of archival FFPE tumor tissue sample (if available) prior to 
start of study treatment for assessment of the tumor microenvironment for 
exploratory biomarkers. 
 Blood sample obtained for exploratory biomarkers  
 Tumor assessment (CT/ MRI) for determination of measurable disease 
(RECIST v1.1) 
 Chest, abdomen, and pelvis (head, if clinically indicated) CT (preferred method) 
or MRI (if clinically indicated). If the chest and/or head CT/MRI is clear at 
screening, repeat imaging is not required in the absence of clinical indication 
requiring follow-up. PET/CT may be used according to RECIST v1.1 guidelines. 
 Scans performed prior to informed consent as part of routine clinical management 
are acceptable for use as initial tumor imaging if they are of diagnostic quality and 
are performed within 28 days prior to first dose date. 
 Bone scans performed per standard of care. 
 Laboratory assessments: 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 229 of 259 
 CBC 
 Serum chemistry 
 Coagulation 
 Serum pregnancy test for women of childbearing potential only within 72 hours of 
first dose of study treatment 
 Serum tumor markers (if indicated) 
 Urinalysis  
  TSH, T3 or FT3, and FT4 or equivalent tests if TSH, T3 or FT3, or FT4 are not 
available 
 ECG 
 Physical examination 
 Vital signs (BP, pulse, and temperature) and weight 
 Height 
 ECOG performance status 
 Concomitant medications 
 AE monitoring 
11.2.2. 
Cycle 1 
At Cycle 1, all patients will undergo the procedures as outlined in the following subsections. 
Day 1 
 Inclusion/exclusion criteria review 
 Blood sample to be obtained predose for exploratory biomarkers  
 Blood samples for PK and ADA assessment 
 Laboratory assessments (if screening assessments were performed within 72 hours of 
Day 1, repeat testing is not required): 
 CBC 
 Serum chemistry 
 Serum tumor markers (if indicated) 
 Urinalysis 
 ECG 
 Parts A and C only: ECG monitoring to be conducted 30 minutes prior to and 
2 hours after the niraparib dose 
 Symptom-directed physical examination 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 230 of 259 
 Vital signs (BP, pulse, and temperature) and weight 
 Concomitant medications 
 AE monitoring 
 TSR-042 study treatment administered at the study site after other visit procedures 
completed 
 For patients in Parts G and H, nab-paclitaxel infusion will be administered after other 
visit procedures are completed on Day 1 of every week (Q1W). 
 Parts A and C only: niraparib first dose administered at the study site after 
completion of all infusions 
 Parts B and D only: carboplatin-paclitaxel infusion administered at the study site 
after completion of TSR-042 infusion (Order of administration: TSR-042 infusion 
followed by paclitaxel infusion followed by carboplatin infusion) 
 Parts C and D only: bevacizumab infusion administered at the study site following 
carboplatin infusion 
 Part E only: carboplatin-pemetrexed infusion administered at the study site after 
completion of TSR-042 infusion (Order of administration: TSR-042 infusion 
followed by pemetrexed infusion followed by carboplatin infusion)  
 Part F only: TSR-022 infusion administered at the study site after completion of 
TSR-042 infusion, followed by carboplatin-pemetrexed infusion (Order of 
administration: TSR-042 infusion followed by TSR-022 infusion followed by 
pemetrexed infusion followed by carboplatin infusion) 
 Part G only: carboplatin–nab-paclitaxel infusion administered at the study site after 
completion of TSR-042 infusion (Order of administration: TSR-042 infusion 
followed by nab-paclitaxel infusion followed by carboplatin infusion) 
 Part H only: TSR-022 infusion administered at the study site after completion of 
TSR-042 infusion, followed by carboplatin–nab-paclitaxel infusion (Order of 
administration: TSR-042 infusion followed by TSR-022 infusion followed by 
nab-paclitaxel infusion followed by carboplatin infusion) 
 Part I only: TSR-022 infusion administered at the study site after completion of 
TSR-042 infusion, followed by carboplatin-paclitaxel infusion (Order of 
administration: TSR-042 infusion followed by TSR-022 infusion followed by 
paclitaxel infusion followed by carboplatin infusion) 
Day 2 
 Blood samples for PK and ADA assessment 
Day 3 
 Parts B, D, E, F, G, H, and I: blood samples for PK assessment 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 231 of 259 
Day 4 
 Parts B, D, G, H, and I: blood samples for PK assessment 
Day 5 
 Blood samples for PK and ADA assessment 
Day 8 
Visit to be conducted at the study site to include the following: 
 Blood samples for PK and ADA assessment  
 CBC 
 Vital signs (BP, pulse, and temperature) and weight 
 Concomitant medications 
 AE monitoring 
Day 15 
 Blood samples for PK and ADA assessment 
 Laboratory assessments: 
 CBC 
 Serum chemistry 
 Coagulation  
 Symptom-directed physical examination 
 Vital signs (BP, pulse, and temperature) and weight 
 Concomitant medications 
 AE monitoring 
 For Parts E, F, G, H, and I: blood samples to be obtained predose for exploratory 
biomarkers 
11.2.3. 
Cycles 2 through 6 and Subsequent Cycles 
 Beginning at Cycle 2, all patients will undergo Day 1 procedures at every 21-day 
cycle as outlined below. At specific cycles, patients will undergo additional 
procedures as described in the subsequent subsections.  
 For patients in Parts G and H, nab-paclitaxel infusion will be administered after other 
visit procedures are completed on Day 1 of every week (Q1W). 
 On-treatment and progression biopsies are optional. In the subset of patients who 
undergo serial biopsies, biomarkers will be evaluated in new tumor samples obtained 
at approximately 4 to 6 weeks after initiating study treatment and, whenever possible, 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 232 of 259 
at the time of disease progression (EOT visit) (note: while the biopsy is voluntary, it 
is highly encouraged). A core biopsy is recommended (details are provided in the 
Study Laboratory Manual). 
Day 1 
 Tumor assessment (RECIST v1.1) 
 Radiographic evaluations (CT or MRI of the chest, abdomen, and pelvis) and 
appropriate testing of serum tumor markers, where applicable (to assess the extent 
of disease), will be conducted at 12 weeks after receiving the first dose of study 
treatment (i.e., within 1 week prior to Day 1 of Cycle 5) and every 12 weeks 
(84 ± 10 days) thereafter until progression while on study treatment independent 
of cycle delays or dose interruptions, or at any time when progression of disease 
is suspected. CT or MRI of the head will be conducted if clinically indicated; 
bone scans will be conducted per standard of care. If a patient discontinues 
treatment for a reason other than progression, death, withdrawal of consent, or 
loss to follow-up, radiographic scans and serum tumor markers should continue at 
the specified intervals. 
 Per RECIST v1.1, CR or PR should be confirmed; tumor imaging for 
confirmation of response should be confirmed;  tumor imaging for confirmation 
of response may be performed at the earliest 4 weeks after the first indication of 
response or at the next scheduled scan (i.e., 12 weeks later), whichever is 
clinically indicated. 
 Laboratory assessments (may be done within 24 hours prior to the visit): 
 CBC 
 Serum chemistry 
 Coagulation (Day 1 of Cycles 2 and 3 only) 
 Urine pregnancy test for females of childbearing potential conducted every 
3 cycles for duration of study (i.e., Cycle 4, Cycle 7, etc.). 
 Serum tumor markers (if indicated in conjunction with tumor assessment per 
RECIST v1.1) 
 Urinalysis 
 TSH, T3 or FT3, and FT4 (performed Q6W beginning at Day 1 of Cycle 2) or 
equivalent tests if TSH, T3 or FT3, or FT4 are not available 
 Symptom-directed physical examination 
 Vital signs (BP, pulse, and temperature) and weight 
 ECOG performance status 
 Concomitant medications 
 AE monitoring 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 233 of 259 
 Parts A, B, C, and D only: TSR-042 study treatment administered at the study site 
after other visit procedures are completed on Day 1 of every 21-day cycle (Q3W) for 
the first 4 cycles and on Day 1 of every other cycle (Q6W) thereafter 
 Parts E, F, G, H, and I only: TSR-042 study treatment administered at the study site 
after other visit procedures are completed on Day 1 of every 21-day cycle (Q3W) 
 Parts A and C only: niraparib first dose administered at the study site after 
completion of all infusions 
 Parts B and D only: carboplatin-paclitaxel infusion administered at the study site 
after completion of TSR-042 infusion (Order of administration: TSR-042 infusion 
followed by paclitaxel infusion followed by carboplatin infusion) 
 Parts C and D only: bevacizumab infusion administered at the study site following 
carboplatin infusion 
 Part E only: carboplatin-pemetrexed infusion administered at the study site after 
completion of TSR-042 infusion (Order of administration: TSR-042 infusion 
followed by pemetrexed infusion followed by carboplatin infusion)  
 Part F only: TSR-022 infusion administered at the study site after completion of 
TSR-042 infusion, followed by carboplatin-pemetrexed infusion (Order of 
administration: TSR-042 infusion followed by TSR-022 infusion followed by 
pemetrexed infusion followed by carboplatin infusion) 
 Part G only: carboplatin–nab-paclitaxel infusion administered at the study site after 
completion of TSR-042 infusion (Order of administration: TSR-042 infusion 
followed by nab-paclitaxel infusion followed by carboplatin infusion) 
 Part H only: TSR-022 infusion administered at the study site after completion of 
TSR-042 infusion, followed by carboplatin–nab-paclitaxel infusion (Order of 
administration: TSR-042 infusion followed by TSR-022 infusion followed by 
nab-paclitaxel infusion followed by carboplatin infusion) 
 Part I only: TSR-022 infusion administered at the study site after completion of 
TSR-042 infusion, followed by carboplatin-paclitaxel infusion (Order of 
administration: TSR-042 infusion followed by TSR-022 infusion followed by 
paclitaxel infusion followed by carboplatin infusion) 
11.2.3.1. Cycle 2 
On-treatment biopsies are optional. In the subset of patients who undergo serial biopsies, 
biomarkers will be evaluated in new tumor samples obtained 4 to 6 weeks following Dose 1 (will 
fall within Cycle 2 and Cycle 3).  
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 Blood sample to be obtained predose for exploratory biomarkers 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 234 of 259 
 Blood samples for PK and ADA assessment 
 ECG – Parts A and C only: ECG monitoring 30 minutes prior to and 2 hours after 
the niraparib dose  
Day 2 
 Parts A and C only: blood samples for PK assessment 
11.2.3.2. Cycle 4 
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment 
 For Parts E, F, G, H, and I: predose blood samples for exploratory biomarkers 
Day 2 
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment  
Day 5 
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment 
Day 8 
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment  
Day 15 
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment  
11.2.3.3. Cycle 5 
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 Blood samples for PK and TSR-042 and TSR-022 (as applicable) ADA assessment 
 ECG – Parts A and C only: ECG monitoring 30 minutes prior to the niraparib dose  
Day 2 
 Blood samples for PK and TSR-042 and TSR-022 (as applicable) ADA assessment  
Day 3 
 For Parts E, F, G, H, and I: blood samples for PK and TSR-042 and TSR-022 (as 
applicable) ADA assessment 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 235 of 259 
Day 5 
 Blood samples for PK and TSR-042 and TSR-022 (as applicable) ADA assessment 
Day 8 
 Blood samples for PK and TSR-042 and TSR-022 (as applicable) ADA assessment  
Day 15 
 Blood samples for PK and TSR-042 and TSR-022 (as applicable) ADA assessment  
11.2.3.4. Cycle 6 
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment 
 For Parts E, F, G, H, and I: predose blood samples for exploratory biomarkers 
11.2.3.5. Cycle 7 
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment  
11.2.3.6. Cycle 11 
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment 
 ECG – Parts A and C only: ECG monitoring 30 minutes prior to the niraparib dose  
Day 2 
 For Parts A, B, C, and D: blood  samples for PK and TSR-042 and ADA assessment  
Day 5 
 For Parts A, B, C, and D: blood samples for PK and TSR-042 and ADA assessment  
Day 8 
 For Parts A, B, C, and D: blood samples for PK and TSR-042 ADA assessment  
Day 15 
 For Parts A, B, C, and D: blood samples for PK and TSR-042 and ADA assessment  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 236 of 259 
11.2.3.7. Cycle 12 
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 For Parts A, B, C, and D: blood samples for PK and TSR-042 and ADA assessment  
11.2.3.8. Cycle 13 
Day 1 
 All Day 1 procedures as outlined in Section 11.2.3  
 For Parts A, B, C, and D: blood samples for PK and TSR-042 and ADA assessment  
11.2.4. 
End of Treatment 
The following procedures will be performed: 
 Blood samples for exploratory biomarkers upon disease progression (EOT visit) 
 Blood samples for TSR-042 and TSR-022 (as applicable) ADA assessment  
 Tumor assessment (RECIST v1.1) 
 A final set of radiographic images is required at the time of disease progression if 
not done within the last 4 weeks. 
 If a patient discontinues treatment for a reason other than progression or death, 
withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals. 
 Laboratory assessments: 
 CBC 
 Serum chemistry 
 Serum tumor markers (if indicated in conjunction with tumor assessment per 
RECIST v1.1) 
 Urinalysis 
 TSH, T3 or FT3, and FT4 or equivalent 
 ECG 
 Physical examination 
 Vital signs (BP, pulse, and temperature) and weight 
 ECOG performance status 
 Concomitant medications 
 AE monitoring 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 237 of 259 
 Parts A and C only: niraparib study treatment collected 
 Progression biopsies are optional. In the subset of patients who undergo serial 
biopsies, biomarkers will be evaluated in new tumor samples obtained u disease 
progression (EOT visit).  
11.2.5. 
Safety Follow-up  
Safety follow-up visits are required only for those patients who have not started an alternate 
anticancer therapy. Subsequent anticancer therapy information is required to be captured through 
post-treatment if the patient starts alternate anticancer therapy.  
11.2.5.1. 30 Days ± 7 Days Post-treatment 
The following procedures will be performed: 
 Blood sample for TSR-042 and TSR-022 (as applicable) ADA assessment  
 Tumor assessment (RECIST v1.1) 
 If a patient discontinued treatment for a reason other than progression or death, 
withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals. 
 Laboratory assessments (may be done at the study center’s local laboratory or at a 
laboratory local to the patient if the laboratory is included on Food and Drug 
Administration [FDA] Form 1572): 
 Serum chemistry 
 Urine pregnancy 
 Serum tumor markers (if indicated in conjunction with tumor assessment per 
RECIST v1.1) 
 TSH, T3 or FT3, and FT4 (performed only if clinically indicated) or equivalent 
tests if TSH, T3 or FT3, or FT4 are not available  
 Urinalysis 
 Symptom-directed physical examination 
 Vital signs (BP, pulse, and temperature) and weight 
 Concomitant medications 
 AE monitoring: AEs are required to be captured through 30 days after cessation of 
study treatment, SAEs (see Section 10.6.5) are required to be captured through 90 
days after cessation of study treatment (or to a minimum of 30 days post-treatment if 
the patient starts alternate anticancer therapy), AESIs are required to be captured as 
described in Section 10.6.7, and any pregnancies that occur within 180 days post-
treatment are to be captured..  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 238 of 259 
11.2.5.2. 90 Days ± 7 Days Post-treatment  
The following procedures will be performed: 
 Blood sample for TSR-042 and TSR-022 (as applicable) ADA assessment  
 Tumor assessment (RECIST v1.1) 
 If a patient discontinued treatment for a reason other than progression or death, 
withdrawal of consent, or loss to follow-up, radiographic scans and appropriate 
testing of serum tumor markers testing should continue at the specified intervals. 
 Laboratory assessments (may be done at the study center’s local laboratory or at a 
laboratory local to the patient if the laboratory is included on FDA Form 1572): 
 Serum chemistry to be conducted on Day 90 post-treatment (or to a minimum of 
30 days post-treatment if the patient starts alternate anticancer therapy) to assess 
for possible AESIs (see Section 10.6.7). Serum chemistry measurements may be 
done at the study center’s laboratory or at a laboratory local to the patient, if 
approved by the Investigator as an adequate laboratory. 
 Serum tumor markers (if indicated in conjunction with tumor assessment per 
RECIST v1.1) 
 AE monitoring: SAEs (see Section 10.6.5) are required to be captured through 90 
days after cessation of study treatment (or to a minimum of 30 days post-treatment if 
the patient starts alternate anticancer therapy), AESIs are required to be captured as 
described in Section 10.6.7, and any pregnancies that occur within 180 days 
post-treatment are to be captured.  
11.2.6. 
Survival Assessment 
The following procedures will be performed: 
 Tumor assessment (RECIST v1.1) 
 Patients who discontinue treatment for reasons other than disease progression, 
death, withdrawal of consent, or loss to follow-up will be followed for disease 
assessments, including radiographic scans and appropriate testing of serum tumor 
markers testing, per the specified schedule. 
 Laboratory assessments 
 Serum tumor markers (if indicated in conjunction with tumor assessment per 
RECIST v1.1) 
 AE monitoring  
 Any pregnancies that occur within 180 days post-treatment are to be captured. 
 In conjunction with survival assessment, AESI (regardless of causality) and 
study-drug related SAEs will be collected via telephone every 90 ± 14 days after 
the last dose of study treatment. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 239 of 259 
 Survival assessment 
 Patients will be followed up every 90 ± 14 days for survival status. 
11.2.7. 
Unscheduled Visits 
If dose interruption or modification of niraparib is required at any point on study because of 
hematologic toxicity, CBCs will be performed as described in Section 6.4.1.1. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 240 of 259 
12. 
STATISTICAL METHODS 
Details of the statistical analyses presented below will be provided in the study’s statistical 
analysis plan (SAP). A change to the data analysis methods described in the protocol will require 
a protocol amendment only if it alters a principal feature of the protocol. The SAP will be 
finalized prior to database lock. Any changes to the methods described in the plan will be 
described and justified in the final clinical study report. 
All analyses will include summary statistics, including the number and percentage for categorical 
variables and the number of patients, mean, standard deviation, median, minimum, and 
maximum for continuous variables. Time-to-event analyses will be performed using 
Kaplan-Meier methods. Further details will be provided in the study SAP. 
12.1. 
Study Population 
Three analysis populations will be defined as follows: 
 Safety population: All patients who receive any amount of study treatment. All safety 
endpoints will be assessed in the safety population, with the exception of DLT 
assessment, which will include only those patients completing the first cycle of 
therapy, unless the patient discontinued study treatment due to a DLT. Analyses of 
baseline characteristics and the primary analysis of efficacy endpoints will be 
performed on the safety population. 
 PK population: All patients who receive at least 1 dose of study treatment and have at 
least 1 PK sample. 
 ADA population: All patients who receive at least 1 dose of study treatment and have 
provided a predose blood sample and at least 1 postdose blood sample at or after 
96 hours. 
12.2. 
Demographics, Baseline Characteristics, Medical History, and 
Concomitant Medications 
Demographics, baseline characteristics, and medical history information will be summarized by 
dose level for the Safety population using descriptive statistics. No formal statistical comparisons 
will be performed. Demographic, baseline characteristics, and medical history data for each 
patient will be provided in data listings. 
12.3. 
Efficacy Analyses 
12.3.1. 
General Methods 
All analyses will include summary statistics, including number and percentage for categorical 
variables and number of patients, mean, standard deviation, median, minimum, and maximum 
for continuous variables. Two-sided exact 90% confidence intervals (CIs) based on the 
Clopper-Pearson124 will be provided where appropriate. Time-to-event analyses will be 
performed using Kaplan-Meier methods. Comparisons will be made using descriptive statistics.  

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 241 of 259 
12.3.2. 
Secondary Efficacy Parameter(s) 
ORR and DCR will be summarized using descriptive statistics including the number, percentage, 
and 2-sided 90% CIs. 
DOR and PFS will be summarized using Kaplan-Meier analysis, including the number and 
percentage of events, number and percentage of censored patients, and the 25th, 50th, and 75th 
percentiles of times-to-event with 95% CIs. 
12.4. 
Safety Analyses 
The primary endpoints in the safety analysis are as follows: 
 Determination of the RP2D based on the number of DLTs observed during the first 
cycle (i.e., during the first 21 days of treatment [Day 1 to Day 21 of Cycle 1]). 
 Incidence of TEAEs occurring while patients are on treatment or up to 30 days after 
the last dose of study treatment 
 Incidence of SAEs and AESIs occurring while patients are on study treatment or up to 
90 days after the last dose of study treatment 
 Changes in clinical laboratory parameters (hematology, serum chemistry, 
coagulation, thyroid function, and urinalysis), vital signs, ECOG performance status, 
ECG parameters (including QTc calculated using QTcF), physical examinations, and 
use of concomitant medications 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding 
system and displayed in tables and data listings using system organ class and preferred term. 
Analyses of AEs will be performed for those events that are considered treatment-emergent, 
where treatment-emergent is defined per protocol as any AE with onset beginning at the day of 
first administration of study treatment, throughout the treatment period until 30 days after the last 
dose of study treatment, any SAE or AESI that occurs through 90 days after cessation of study 
treatment (or to a minimum of 30 days post-treatment if the patient starts alternate anticancer 
therapy), or any event that was present at baseline but worsened in intensity or was subsequently 
considered drug-related by the Investigator through the end of the study. DLTs will be tabulated 
by dose level. 
The number and percentage of patients with any TEAE, with any TEAE assessed by the 
Investigator as related to treatment (definite, probable, or possible relationship), and with any 
SAE will be summarized by treatment group and overall. In these tabulations, each patient will 
contribute only once (i.e., the most related occurrence or the most intense occurrence) to each of 
the incidence rates in the descriptive analysis, regardless of the number of episodes. No formal 
hypothesis-testing analysis of AE incidence rates will be performed. 
The occurrence of and reasons for any requirement for dose interruption or modification will be 
tabulated, and distinguished as to presumptive causality from niraparib, TSR-042, TSR-022, 
carboplatin-paclitaxel, carboplatin-pemetrexed, carboplatin–nab-paclitaxel, or bevacizumab, if 
known. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 242 of 259 
All AEs occurring on-study will be listed in patient data listings. By-patient listings also will be 
provided for the following: patient deaths, SAEs, and AEs leading to withdrawal. 
Additional safety summaries will be provided for clinical laboratory tests, vital signs, ECOG 
performance status, ECGs, physical examinations, and usage of concomitant medications. 
12.5. 
Pharmacokinetic Analyses 
The analysis set for the PK parameters will be the PK population. Non-compartmental methods 
will be used to evaluate the PK characteristics as appropriate. Parameters of interest are AUC, 
minimum observed plasma or serum concentration (Cmin), maximum observed plasma or serum 
concentration (Cmax), clearance (after oral administration [CL/F] and after IV administration 
[CL]), volume of distribution (after oral administration [Vz/F] and after IV administration [Vz]), 
area under the plasma or serum concentration-time curve at steady state (AUCss), minimum 
observed plasma or serum concentration at steady state (Cmin,ss), and maximum observed plasma 
or serum concentration at steady state (Cmax,ss). 
12.6. 
Immunogenicity Analyses 
The analysis set for ADA analyses will be the ADA population. The number and percent of 
patients who become positive for ADAs and who develop neutralizing antibodies will be 
summarized by dose and regimen, by visit, and overall. 
12.7. 
Biomarker Analyses 
The incidence of biomarkers will be summarized using descriptive statistics. Comparisons of 
efficacy endpoints between biomarker subpopulations may be performed. 
12.8. 
Determination of Sample Size 
An initial sample size of approximately 12 to 24 patients is estimated for Part A of the study to 
provide an initial understanding of the incidence of DLTs and safety profiles of TSR-042 and 
niraparib combination treatment.  
A total of approximately 12 patients will be enrolled in Part B of the study to provide an initial 
understanding of the safety profiles of TSR-042 and carboplatin-paclitaxel combination 
treatment. 
A sample size of approximately 6 to 24 patients is estimated for Part C of the study to provide an 
initial understanding of the incidence of DLTs and safety profiles of TSR-042, niraparib and 
bevacizumab combination treatment.  
A total of approximately 6 to 12 patients will be enrolled in Part D of the study to provide an 
initial understanding of the safety profiles of TSR-042, carboplatin-paclitaxel and bevacizumab 
combination treatment. 
A total of approximately 6 to 12 patients will be enrolled in Part E of the study to provide an 
initial understanding of the safety profiles of TSR-042 and carboplatin-pemetrexed combination 
treatment. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 243 of 259 
A total of approximately 6 to 24 patients will be enrolled in Part F of the study to provide an 
initial understanding of the safety profiles of TSR-042, TSR-022, and carboplatin-pemetrexed 
combination treatment. 
A total of approximately 6 to 12 patients will be enrolled in Part G of the study to provide an 
initial understanding of the safety profiles of TSR-042 and carboplatin–nab-paclitaxel 
combination treatment. 
A total of approximately 6 to 24 patients will be enrolled in Part H of the study to provide an 
initial understanding of the safety profiles of TSR-042, TSR-022, and carboplatin–nab-paclitaxel 
combination treatment. 
A total of approximately 6 to 24 patients will be enrolled in Part I of the study to provide an 
initial understanding of the safety profiles of TSR-042, TSR-022, and carboplatin-paclitaxel 
combination treatment. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 244 of 259 
13. 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS 
13.1. 
Data Quality Assurance 
The Sponsor (or designee) will conduct a study initiation visit to verify the qualifications of the 
Investigator, inspect the facilities, and inform the Investigator of responsibilities and procedures 
for ensuring adequate and correct documentation. 
The Investigator must prepare and maintain adequate and accurate records of all observations 
and other data pertinent to the clinical study for each study participant. Frequent communication 
between the clinical site and the Sponsor is essential to ensure that the safety of the study is 
monitored adequately. The Investigator will make all appropriate safety assessments on an 
ongoing basis. The Sponsor’s Medical Monitor may review safety information as it becomes 
available throughout the study.  
All aspects of the study will be carefully monitored with respect to GCP and standard operating 
procedures for compliance with applicable government regulations. The Study Monitor will be 
an authorized individual designated by the Sponsor. The Study Monitor will have access to all 
records necessary to ensure integrity of the data and will periodically review the progress of the 
study with the Investigator. 
13.2. 
Access to Source Data/Documents 
An electronic data capture system to manage data collection will be utilized during this study. 
The electronic data capture system is a software tool designed to ensure quality assurance and 
facilitate data capture during clinical studies. The system is fully compliant with Code of Federal 
Regulations 21 Part 11.  
The Investigator will ensure the accuracy, completeness, and timeliness of the data reported to 
the Sponsor. Data collection processes and procedures will be reviewed and validated to ensure 
completeness, accuracy, reliability, and consistency. A complete audit trail will be maintained of 
all data changes. The Investigator or designee will cooperate with the Sponsor’s representative(s) 
for the periodic review of study documents to ensure the accuracy and completeness of the data 
capture system at each scheduled monitoring visit.  
Electronic consistency checks and manual review will be used to identify any errors or 
inconsistencies in the data. This information will be provided to the respective study sites by 
means of electronic or manual queries.  
The Investigator or designee will prepare and maintain adequate and accurate study documents 
(medical records, ECGs, AEs, and concomitant medication reporting, raw data collection 
forms, etc.) designed to record all observations and other pertinent data for each patient receiving 
study treatment.  
The Investigator will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors, and the IRB/IEC to have direct access to all documents pertaining to the 
study. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 245 of 259 
13.3. 
Archiving Study Documents 
Essential clinical documents will be maintained to demonstrate the validity of the study and the 
integrity of the data collected. Master files should be established at the beginning of the study, 
maintained for the duration of the study, and retained according to the appropriate regulations. 
According to International Council for Harmonisation (ICH) guidelines, essential documents 
should be retained for a minimum of 2 years after the last approval of a marketing application in 
an ICH region and until there are no pending or contemplated marketing applications in an ICH 
region or at least 2 years have elapsed since the formal discontinuation of clinical development 
of the study treatment.  
13.4. 
Good Clinical Practice 
This study will be conducted in accordance with the ICH for GCP and the Declaration of 
Helsinki (Version 2008). The clinical study will also be carried out in accordance with national 
and local regulatory requirement(s).  
13.5. 
Informed Consent 
Before each patient is enrolled in the clinical study, written informed consent will be obtained 
from the patient according to the regulatory and legal requirements of the participating country. 
As part of this procedure, the Investigator must explain orally and in writing the nature, duration, 
and purpose of the study, and the action of the study treatment in such a manner that the patient 
is aware of the potential risks, inconveniences, or AEs that may occur. The patient should be 
informed that he or she is free to withdraw from the study at any time. The patient will receive 
all information that is required by regulatory authorities and ICH guidelines. The Investigator or 
designee will provide the Sponsor with a copy of the IRB/IEC-approved ICF prior to the start of 
the study. 
The ICF must be signed and dated; 1 copy will be given to the patient and the Investigator will 
retain a copy as part of the clinical study records. The Investigator will not undertake any 
investigation specifically required for the clinical study until written consent has been obtained. 
The terms of the consent and when it was obtained must also be documented.  
If a protocol amendment is required, then the ICF may need to be revised to reflect the changes 
to the protocol. If the ICF is revised, it must be reviewed and approved by the responsible 
IRB/IEC and signed by all patients subsequently enrolled in the clinical study as well as those 
currently enrolled in the clinical study. 
13.6. 
Protocol Approval and Amendment 
Before the start of the study, the study protocol and/or other relevant documents will be approved 
by the IEC/IRB/Competent Authorities, in accordance with local legal requirements. The 
Sponsor must ensure that all ethical and legal requirements have been met before the first patient 
is enrolled in the study. 
This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the appropriate personnel, and receive IRB/IEC/Competent Authority 
approval prior to implementation (if appropriate). In the United States, following approval, the 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 246 of 259 
protocol amendment(s) will be submitted to the Investigational New Drug application under 
which the study is being conducted. 
Administrative changes (not affecting the patient benefit/risk ratio) may be made without the 
need for a formal amendment. All amendments will be distributed to all protocol recipients, with 
appropriate instructions. 
13.7. 
Patient Confidentiality and Data Protection 
All clinical study findings and documents will be regarded as confidential. Study documents 
(protocols, IBs, and other material) will be stored appropriately to ensure their confidentiality. 
The Investigator and members of his or her research team (including the IRB/IEC) must not 
disclose such information without prior written approval from the Sponsor, except to the extent 
necessary to obtain informed consent from patients who wish to participate in the study or to 
comply with regulatory requirements.  
The anonymity of participating patients must be maintained. Patients will be specified on study 
documents by their enrollment number or birth date, not by name. Documents that identify the 
patient (e.g., the signed informed consent document) must be maintained in confidence by the 
Investigator. 
13.8. 
Study Monitoring 
Monitoring and auditing procedures approved by the Sponsor will be followed in order to 
comply with GCP guidelines. On-site checking of the eCRFs for completeness and clarity, 
cross-checking with source documents, and clarification of administrative matters will be 
performed. 
The study will be monitored by the Sponsor or its designee. Monitoring will be done by personal 
visits from a representative of the Sponsor (Site Monitor) who will review the eCRFs and source 
documents. The Site Monitor will ensure that the investigation is conducted according to 
protocol design and regulatory requirements by frequent site visits and by communications 
(letter, telephone, and fax). 
All unused study treatment and other study materials will be returned to the Sponsor after the 
clinical phase of the study has been completed. 
13.9. 
Audits and Inspections 
Regulatory authorities, the IRB/IEC, and/or the Sponsor’s clinical quality assurance group, or its 
designee, may request access to all source documents, eCRFs, and other study documentation for 
on-site audit or inspection. Direct access to these documents must be guaranteed by the 
Investigator, who must provide support at all times for these activities. 
13.10. 
Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the Declaration of 
Helsinki. The IRB/IEC will review all appropriate study documentation in order to safeguard the 
rights, safety, and well-being of the patients. The study will only be conducted at sites where 
IRB/IEC approval has been obtained. The protocol, Investigator’s Brochure, informed consent, 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 247 of 259 
advertisements (if applicable), written information given to the patients, safety updates, annual 
progress reports, and any revisions to these documents will be provided to the IRB/IEC by the 
Investigator. 
13.11. 
Publication Policy 
Information regarding publication of study results is contained in the Clinical Trial Agreement 
for this study. 
13.12. 
Study Committee  
A Study Committee comprised of Investigators and Sponsor representatives will be established 
to provide review and assessment of the study data on an ongoing basis and to safeguard the 
interest and safety of the participating patients in the study. The details on membership, key 
responsibilities, and corresponding procedures are provided in the Study Committee charter.  
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 248 of 259 
14. 
LIST OF REFERENCES 
1. 
Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors 
from BRCA mutation carriers. N Engl J Med. 2009;361(2):123-134. 
2. 
De Lorenzo SB, Patel AG, Hurley RM, Kaufmann SH. The Elephant and the Blind Men: 
Making Sense of PARP Inhibitors in Homologous Recombination Deficient Tumor Cells. 
Front Oncol. 2013;3:228. 
3. 
Jones P, Wilcoxen K, Rowley M, Toniatti C. Niraparib: A Poly(ADP-ribose) Polymerase 
(PARP) Inhibitor for the Treatment of Tumors with Defective Homologous 
Recombination. J Med Chem. 2015;58(8):3302-3314. 
4. 
Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-
grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a 
phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12(9):852-
861. 
5. 
Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev 
Cancer. 2004;4(10):814-819. 
6. 
Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. 
Nature. 2011;474(7353):609-615. 
7. 
Timms KM, Abkevich V, Hughes E, et al. Association of BRCA1/2 defects with 
genomic scores predictive of DNA damage repair deficiency among breast cancer 
subtypes. Breast Cancer Res. 2014;16(6):475. 
8. 
Turner NC, Ashworth A. Biomarkers of PARP inhibitor sensitivity. Breast Cancer Res 
Treat. 2011;127(1):283-286. 
9. 
Kummar S, Ji J, Morgan R, et al. A phase I study of veliparib in combination with 
metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. 
Clin Cancer Res. 2012;18(6):1726-1734. 
10. 
Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-
sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382-1392. 
11. 
Sandhu SK, Schelman WR, Wilding G, et al. The poly(ADP-ribose) polymerase inhibitor 
niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a 
phase 1 dose-escalation trial. Lancet Oncol. 2013;14(9):882-892. 
12. 
Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib 
in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-
concept trial. Lancet. 2010;376(9737):235-244. 
13. 
Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-
Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016;375(22):2154-2164. 
14. 
Pujade-Lauraine E, Ledermann JA, Penson RT, et al. Treatment with olaparib 
monotherapy in the maintenance setting significantly improves progression-free survival 
in patients with platinum-sensitive relapsed ovarian cancer: Results from the phase III 
SOLO2 study. 48th Annual Meeting for the Society of Gynecologic Onocolgy. March 
12-15, 2017. National Harbor, Maryland. Abstract# LBA-2. 
15. 
Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with 
a Germline BRCA Mutation. N Engl J Med. 2017. 
16. 
Disis ML. Immune regulation of cancer. J Clin Oncol. 2010;28(29):4531-4538. 
17. 
Mei Z, Liu Y, Liu C, et al. Tumour-infiltrating inflammation and prognosis in colorectal 
cancer: systematic review and meta-analysis. Br J Cancer. 2014;110(6):1595-1605. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 249 of 259 
18. 
Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G. Harmonization of 
the evaluation of tumor infiltrating lymphocytes (TILs) in breast cancer: 
recommendations by an international TILs-working group 2014. Annals of oncology : 
official journal of the European Society for Medical Oncology / ESMO. 2014;Sep 11. 
19. 
Schatton T, Scolyer RA, Thompson JF, Mihm MC, Jr. Tumor-infiltrating lymphocytes 
and their significance in melanoma prognosis. Methods Mol Biol. 2014;1102:287-324. 
20. 
Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW. The prognostic influence 
of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br 
J Cancer. 2011;105(1):93-103. 
21. 
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in 
cancer suppression and promotion. Science. 2011;331(6024):1565-1570. 
22. 
Bremnes RM, Al-Shibli K, Donnem T, et al. The role of tumor-infiltrating immune cells 
and chronic inflammation at the tumor site on cancer development, progression, and 
prognosis: emphasis on non-small cell lung cancer. J Thorac Oncol. 2011;6(4):824-833. 
23. 
Talmadge JE. Immune cell infiltration of primary and metastatic lesions: mechanisms and 
clinical impact. Semin Cancer Biol. 2011;21(2):131-138. 
24. 
Shirabe K, Motomura T, Muto J, et al. Tumor-infiltrating lymphocytes and hepatocellular 
carcinoma: pathology and clinical management. Int J Clin Oncol. 2010;15(6):552-558. 
25. 
Nosho K, Baba Y, Tanaka N, et al. Tumour-infiltrating T-cell subsets, molecular changes 
in colorectal cancer, and prognosis: cohort study and literature review. J Pathol. 
2010;222(4):350-366. 
26. 
Bellati F, Visconti V, Napoletano C, et al. Immunology of gynecologic neoplasms: 
analysis of the prognostic significance of the immune status. Curr Cancer Drug Targets. 
2009;9(4):541-565. 
27. 
Oble DA, Loewe R, Yu P, Mihm MC, Jr. Focus on TILs: prognostic significance of 
tumor infiltrating lymphocytes in human melanoma. Cancer Immun. 2009;9:3. 
28. 
Uppaluri R, Dunn GP, Lewis JS, Jr. Focus on TILs: prognostic significance of tumor 
infiltrating lymphocytes in head and neck cancers. Cancer Immun. 2008;8:16. 
29. 
Dunn GP, Dunn IF, Curry WT. Focus on TILs: Prognostic significance of tumor 
infiltrating lymphocytes in human glioma. Cancer Immun. 2007;7:12. 
30. 
Chang WJ, Du Y, Zhao X, Ma LY, Cao GW. Inflammation-related factors predicting 
prognosis of gastric cancer. World J Gastroenterol. 2014;20(16):4586-4596. 
31. 
Preston CC, Maurer MJ, Oberg AL, et al. The ratios of CD8+ T cells to CD4+CD25+ 
FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous 
ovarian cancer. PLoS One. 2013;8(11):e80063. 
32. 
Yoon HH, Orrock JM, Foster NR, Sargent DJ, Smyrk TC, Sinicrope FA. Prognostic 
impact of FoxP3+ regulatory T cells in relation to CD8+ T lymphocyte density in human 
colon carcinomas. PLoS One. 2012;7(8):e42274. 
33. 
Kim ST, Jeong H, Woo OH, et al. Tumor-infiltrating lymphocytes, tumor characteristics, 
and recurrence in patients with early breast cancer. Am J Clin Oncol. 2013;36(3):224-
231. 
34. 
Mathai AM, Kapadia MJ, Alexander J, Kernochan LE, Swanson PE, Yeh MM. Role of 
Foxp3-positive tumor-infiltrating lymphocytes in the histologic features and clinical 
outcomes of hepatocellular carcinoma. Am J Surg Pathol. 2012;36(7):980-986. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 250 of 259 
35. 
Liu F, Lang R, Zhao J, et al. CD8(+) cytotoxic T cell and FOXP3(+) regulatory T cell 
infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer 
Res Treat. 2011;130(2):645-655. 
36. 
Kirk R. Risk factors. CD8+:FOXP3+ cell ratio is a novel survival marker for colorectal 
cancer. Nat Rev Clin Oncol. 2010;7(6):299. 
37. 
Pedoeem A, Azoulay-Alfaguter I, Strazza M, Silverman GJ, Mor A. Programmed death-1 
pathway in cancer and autoimmunity. Clin Immunol. 2014;153(1):145-152. 
38. 
Zhang X, Schwartz JC, Guo X, et al. Structural and functional analysis of the 
costimulatory receptor programmed death-1. Immunity. 2004;20(3):337-347. 
39. 
Lazar-Molnar E, Yan Q, Cao E, Ramagopal U, Nathenson SG, Almo SC. Crystal 
structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. 
Proc Natl Acad Sci U S A. 2008;105(30):10483-10488. 
40. 
Lin DY, Tanaka Y, Iwasaki M, et al. The PD-1/PD-L1 complex resembles the antigen-
binding Fv domains of antibodies and T cell receptors. Proc Natl Acad Sci U S A. 
2008;105(8):3011-3016. 
41. 
Cheng X, Veverka V, Radhakrishnan A, et al. Structure and interactions of the human 
programmed cell death 1 receptor. J Biol Chem. 2013;288(17):11771-11785. 
42. 
Sheppard KA, Fitz LJ, Lee JM, et al. PD-1 inhibits T-cell receptor induced 
phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to 
PKCtheta. FEBS Lett. 2004;574(1-3):37-41. 
43. 
Ott PA, Hodi FS, Robert C. CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic 
modalities with durable clinical benefit in melanoma patients. Clin Cancer Res. 
2013;19(19):5300-5309. 
44. 
Yao S, Chen L. PD-1 as an immune modulatory receptor. Cancer Journal. 
2014;20(4):26. 
45. 
Nishimura H, Agata Y, Kawasaki A, et al. Developmentally regulated expression of the 
PD-1 protein on the surface of double-negative (CD4−CD8−) thymocytes. Int Immunol. 
1996;8(5):773-780. 
46. 
Huang X, Venet F, Wang YL, et al. PD-1 expression by macrophages plays a pathologic 
role in altering microbial clearance and the innate inflammatory response to sepsis. Proc 
Natl Acad Sci U S A. 2009;106(15):6303-6308. 
47. 
Pena-Cruz V, McDonough SM, Diaz-Griffero F, Crum CP, Carrasco RD, Freeman GJ. 
PD-1 on immature and PD-1 ligands on migratory human Langerhans cells regulate 
antigen-presenting cell activity. J Invest Dermatol. 2010;130(9):2222-2230. 
48. 
Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and 
immunity. Annu Rev Immunol. 2008;26:677-704. 
49. 
Guan J, Lim KS, Mekhail T, Chang CC. Programmed Death Ligand-1 (PD-L1) 
Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player 
Against Various Cancers. Arch Pathol Lab Med. 2017;141(6):851-861. 
50. 
Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with 
B7-h1 expression in human melanocytic lesions supports an adaptive resistance 
mechanism of immune escape. Sci Transl Med. 2012;4(127):127ra137. 
51. 
Sanmamed MF, Chen L. Inducible expression of B7-H1 (PD-L1) and its selective role in 
tumor site immune modulation. Cancer J. 2014;20(4):256-261. 
52. 
Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to 
activate anti-tumor immunity. Curr Opin Immunol. 2012;24(2):207-212. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 251 of 259 
53. 
Monney L, Sabatos CA, Gaglia JL, et al. Th1-specific cell surface protein Tim-3 
regulates macrophage activation and severity of an autoimmune disease. Nature. 
2002;415(6871):536-541. 
54. 
Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting 
Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. 
J Exp Med. 2010;207(10):2187-2194. 
55. 
Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ. Anti-TIM3 
antibody promotes T cell IFN-gamma-mediated antitumor immunity and suppresses 
established tumors. Cancer Res. 2011;71(10):3540-3551. 
56. 
Dardalhon V, Anderson AC, Karman J, et al. Tim-3/galectin-9 pathway: regulation of 
Th1 immunity through promotion of CD11b+Ly-6G+ myeloid cells. J Immunol. 
2010;185(3):1383-1392. 
57. 
Baitsch L, Legat A, Barba L, et al. Extended co-expression of inhibitory receptors by 
human CD8 T-cells depending on differentiation, antigen-specificity and anatomical 
localization. PLoS One. 2012;7(2):e30852. 
58. 
Gros A, Robbins PF, Yao X, et al. PD-1 identifies the patient-specific CD8(+) tumor-
reactive repertoire infiltrating human tumors. J Clin Invest. 2014;124(5):2246-2259. 
59. 
Thommen DS, Schreiner J, Muller P, et al. Progression of Lung Cancer Is Associated 
with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory 
Receptors. Cancer Immunol Res. 2015;3(12):1344-1355. 
60. 
Jie HB, Gildener-Leapman N, Li J, et al. Intratumoral regulatory T cells upregulate 
immunosuppressive molecules in head and neck cancer patients. Br J Cancer. 
2013;109(10):2629-2635. 
61. 
Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is 
associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J 
Exp Med. 2010;207(10):2175-2186. 
62. 
Sakuishi K, Ngiow SF, Sullivan JM, et al. TIM3FOXP3 regulatory T cells are tissue-
specific promoters of T-cell dysfunction in cancer. Oncoimmunology. 2013;2(4):e23849. 
63. 
Brabec V, Kasparkova J. Modifications of DNA by platinum complexes. Relation to 
resistance of tumors to platinum antitumor drugs. Drug Resist Updat. 2005;8(3):131-146. 
64. 
Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation 
of a simple formula based on renal function. J Clin Oncol. 1989;7(11):1748-1756. 
65. 
Mekhail TM, Markman M. Paclitaxel in cancer therapy. Expert Opin Pharmacother. 
2002;3(6):755-766. 
66. 
Moore KN, Herzog TJ, Lewin S, et al. A comparison of cisplatin/paclitaxel and 
carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol 
Oncol. 2007;105(2):299-303. 
67. 
Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens 
for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92-98. 
68. 
Dizon DS. Treatment options for advanced endometrial carcinoma. Gynecol Oncol. 
2010;117(2):373-381. 
69. 
Molin Y, Fayette J. Current chemotherapies for recurrent/metastatic head and neck 
cancer. Anticancer Drugs. 2011;22(7):621-625. 
70. 
Goding SR, Wilson KA, Xie Y, et al. Restoring immune function of tumor-specific 
CD4+ T cells during recurrence of melanoma. J Immunol. 2013;190(9):4899-4909. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 252 of 259 
71. 
Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus 
gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with 
advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543-3551. 
72. 
Ciuleanu T, Brodowicz T, Zielinski C, et al. Maintenance pemetrexed plus best 
supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a 
randomised, double-blind, phase 3 study. Lancet. 2009;374(9699):1432-1440. 
73. 
Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus 
best supportive care versus placebo plus best supportive care after induction therapy with 
pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer 
(PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 
2012;13(3):247-255. 
74. 
FDA. FULL PRESCRIBING INFORMATION - ABRAXANE® for Injectable 
Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-
bound) In:2013. 
75. 
Desai N, Trieu V, Yao Z, et al. Increased antitumor activity, intratumor paclitaxel 
concentrations, and endothelial cell transport of cremophor free, albumin-bound 
paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res. 
2006;12:1317-1324. 
76. 
Nyman DW, Campbell KJ, Hersh E, et al. Phase I and pharmacokinetics trial of ABI-007, 
a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic 
malignancies. J Clin Oncol. 2005;23(31):7785-7793. 
77. 
Satouchi M, Okamoto I, Sakai H, et al. Efficacy and safety of weekly nab-paclitaxel plus 
carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 
2013;81(1):97-101. 
78. 
Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-
bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with 
breast cancer. J Clin Oncol. 2005;23(31):7794-7803. 
79. 
Socinski MA, Manikhas GM, Stroyakhovsky DL, et al. A dose finding study of weekly 
and every-3-week nab-Paclitaxel followed by carboplatin as first-line therapy in patients 
with advanced non-small cell lung cancer. J Thorac Oncol. 2010;5(6):852-861. 
80. 
Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination 
with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in 
patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin 
Oncol. 2012;30(17):2055-2062. 
81. 
Miller A, Mahtani KR, Waterfield MA, Timms A, Misbah SA, Luqmani RA. Is 
rheumatoid factor useful in primary care? A retrospective cross-sectional study. Clin 
Rheumatol. 2013;32(7):1089-1093. 
82. 
Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary 
treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473-2483. 
83. 
Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. 
N Engl J Med. 2011;365(26):2484-2496. 
84. 
Xing D, Orsulic S. A mouse model for the molecular characterization of BRCA1-
associated ovarian carcinoma. Cancer Res. 2006;66(18):8949-8953. 
85. 
Huang J, Wang L, Cong Z, et al. The PARP1 inhibitor BMN 673 exhibits 
immunoregulatory effects in a BRCA1(-/-) murine model of ovarian cancer. Biochem 
Biophys Res Commun. 2015;463(4):551-556. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 253 of 259 
86. 
Meade M. Efficacy evaluation of niraparib and TSR-042 alone and in combination 
against subcutaneous BRKras-luc murine ovarian carcinoma in female FVB mice. 
Molecular Imaging;2016. TESA-201605b (MI2688). 
87. 
Mills G. Efficacy of niraparib as a single agent and in combination with PD-1 antibody 
in LPA1-T22 tumor model. TESARO, Inc.;2017. 
88. 
Efficacy and PD study in KLN205 subcutaneous lung squamous cell cancer model. 
Pharmaron;2016. PH-ON-TSB-KLN205-09032015. 
89. 
Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunological effects of 
conventional chemotherapy and targeted anticancer agents. Cancer Cell. 2015;28(6):690-
714. 
90. 
Hato SV, Khong A, de Vries IJ, Lesterhuis WJ. Molecular pathways: the immunogenic 
effects of platinum-based chemotherapeutics. Clin Cancer Res. 2014;20(11):2831-2837. 
91. 
Senovilla L, Vitale I, Martins I, et al. An immunosurveillance mechanism controls cancer 
cell ploidy. Science. 2012;337(6102):1678-1684. 
92. 
Sevko A, Michels T, Vrohlings M, et al. Antitumor effect of paclitaxel is mediated by 
inhibition of myeloid-derived suppressor cells and chronic inflammation in the 
spontaneous melanoma model. J Immunol. 2013;190(5):2464-2471. 
93. 
Liechtenstein T, Perez-Janices N, Gato M, et al. A highly efficient tumor-infiltrating 
MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents 
the need for tumor establishment in mice. Oncotarget. 2014;5(17):7843-7857. 
94. 
Pfannenstiel LW, Lam SS, Emens LA, Jaffee EM, Armstrong TD. Paclitaxel enhances 
early dendritic cell maturation and function through TLR4 signaling in mice. Cell 
Immunol. 2010;263(1):79-87. 
95. 
Rizvi NA, Hellmann MD, Brahmer JR, et al. Nivolumab in Combination With Platinum-
Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell 
Lung Cancer. J Clin Oncol. 2016;34(25):2969-2979. 
96. 
Louwen R, Horst-Kreft D, de Boer AG, et al. A novel link between Campylobacter jejuni 
bacteriophage defence, virulence and Guillain-Barre syndrome. Eur J Clin Microbiol 
Infect Dis. 2013;32(2):207-226. 
97. 
Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for 
non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542-2550. 
98. 
Tewari KS, Sill MW, Long HJ, 3rd, et al. Improved survival with bevacizumab in 
advanced cervical cancer. N Engl J Med. 2014;370(8):734-743. 
99. 
Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without 
pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, 
phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 
2016;17(11):1497-1508. 
100. 
Paz-Ares LG, Luft A, Tafreshi A, et al. Phase 3 study of carboplatin-paclitaxel/nab-
paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with 
metastatic squamous (Sq) non-small cell lung cancer (NSCLC). Paper presented at: 
ASCO Annual Meeting2018. 
101. 
Jotte RM, Cappuzzo F, Vynnychenko I, et al. IMpower131: Primary PFS and safety 
analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or 
nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous 
NSCLC. Paper presented at: ASCO Annual Meeting2018. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 254 of 259 
102. 
Mirza MR, Mortensen CE, Christensen RdP, et al. ENGOT-OV24/AVANOVA1 - A 
Phase 1 study of bevacizumab in combination with niraparib in patients with platinum-
sensitive epithelial ovarian cancer. Poster presented at the American Society of Clinical 
Oncology (ASCO) meeting June 3-7, 2016 in Chicago, Illinois. 
103. 
Zimmer AP, C; Cao, L; Kohn, E; Lipkowitz, S; Annuziata, C; Trepel, J; Lee, M; 
Mikkilineni, L; Gatti-Mays, M; Nunes, A; Soltani, S; Figg, W.D.; Houston, N; Nichols, 
E; Lee, J. A phase I study of durvalumab (D) in combination with olaparib (O) and 
cediranib (C) in recurrent women’s cancers- ESMO 2017 Congress. Annals of Oncology 
2017;28(Supplement 5). 
104. 
Lee J-m, Zimmer ADS, Lipkowitz S, et al. Phase I study of the PD-L1 inhibitor, 
durvalumab (MEDI4736; D) in combination with a PARP inhibitor, olaparib (O) or a 
VEGFR inhibitor, cediranib (C) in women's cancers (NCT02484404). Journal of Clinical 
Oncology. 2016;34(15_suppl):3015-3015. 
105. 
Friedlander M, Meniawy T, Markman B, et al. A phase 1b study of the anti-PD-1 
monoclonal antibody BGB-A317 (A317) in combination with the PARP inhibitor BGB-
290 (290) in advanced solid tumors. J Clin Oncol 35, 2017 (suppl; abstr 3013). 
106. 
Gadgeel SM, Stevenson J, Langer CJ, et al. Pembrolizumab (pembro) plus chemotherapy 
as front-line therapy for advanced NSCLC: KEYNOTE-021 cohorts A-C. Journal of 
Clinical Oncology. 2016;34(15_suppl):9016-9016. 
107. 
Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse 
events in patients treated with immune checkpoint inhibitor therapy: American Society of 
Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;77. 
108. 
Costa R, Carneiro BA, Agulnik M, et al. Toxicity profile of approved anti-PD-1 
monoclonal antibodies in solid tumors: a systematic review and meta-analysis of 
randomized clinical trials. Oncotarget. 2017;8(5):8910-8920. 
109. 
NCCN. Clinical Practice Guidelines in Oncology: Ovarian Cancer. National 
Comprehensive Cancer Network; 2015. 
110. 
Colombo N, Creutzberg C, Amant F, et al. ESMO-ESGO-ESTRO consensus conference 
on endometrial cancer: diagnosis, treatment and follow-up. Ann Oncol. 2016;27(1):16-41. 
111. 
AVASTIN® (bevacizumab) solution for intravenous infusion [prescribing information]. 
San Francisco, CA: Genetech Inc.; 2016. 
112. 
Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the 
use of white blood cell growth factors: an evidence-based clinical practice guideline. J 
Clin Oncol. 2006;24(19):3187-3205. 
113. 
ZEJULATM (niraparib) capsules, for oral use [prescribing information]. Waltham, MA: 
TESARO.; 2017. 
114. 
Teva Parenteral Medicines. Carboplatin injection package insert. In:2011. 
115. 
WG Critical Care. Paclitaxel injection, USP [package insert]. In. Paramus, NJ2013. 
116. 
Eli Lilly and Company. ALIMTA (pemetrexed disodium) [package insert]. In. 
Indianapolis, IN2008. 
117. 
Wang SC, Li YH, Piao HL, et al. PD-1 and Tim-3 pathways are associated with 
regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy. Cell 
Death Dis. 2015;6:e1738. 
118. 
Wang S, Cao C, Piao H, et al. Tim-3 protects decidual stromal cells from toll-like 
receptor-mediated apoptosis and inflammatory reactions and promotes Th2 bias at the 
maternal-fetal interface. Sci Rep. 2015;5:9013. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 255 of 259 
119. 
D'Addio F, Riella LV, Mfarrej BG, et al. The link between the PDL1 costimulatory 
pathway and Th17 in fetomaternal tolerance. J Immunol. 2011;187(9):4530-4541. 
120. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 
121. 
Nishino M, Tirumani SH, Ramaiya NH, Hodi FS. Cancer immunotherapy and immune-
related response assessment: the role of radiologists in the new arena of cancer treatment. 
Eur J Radiol. 2015;84(7):1259-1268. 
122. 
U.S. Department of Health and Human Services. Guidance on informed consent for in 
vitro diagnostic device studies using leftover human specimens that are not individually 
identifiable. In: Administration FaD, Health CfDaR, Health OoIVDaR, Devices DoM, 
eds2006. 
123. 
Committee for Human Medicinal Products (CHMP). Reflection paper on 
pharmacogenomic samples, testing and data handling. 2007. 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/
WC500003864.pdf. 
124. 
Clopper C, Pearson E. The Use of Confidence or Fiducial Limits Illustrated in the Case 
of the Binomial. Biometrika. 1934;26(4):404-413. 
125. 
Menissier de Murcia J, Ricoul M, Tartier L, et al. Functional interaction between PARP-1 
and PARP-2 in chromosome stability and embryonic development in mouse. EMBO J. 
2003;22(9):2255-2263. 
126. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. 
 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 256 of 259 
APPENDIX A. DRUGS KNOWN TO INHIBIT OR INDUCE OR ARE 
SUBSTRATES OF CYP450 ISOZYMES 
Table 57: 
Drugs Known to Inhibit or Induce or are Substrates of CYP3A4 or CYP2C8 
Category 
CYP3A4 
CYP2C8 
Inhibitor 
Atazanavir, clarithromycin, indinavir, itraconazole, 
ketoconazole, nefazodone, nelfinavir, ritonavir, 
saquinavir, and telithromycin 
Gemfibrozil 
Inducer 
Rifampin and carbamazepine 
Rifampin  
Substrate 
Midazolam, buspirone, felodipine, lovastatin, 
eletriptan, sildenafil, simvastatin, and triazolam 
Repaglinide and rosiglitazone 
Source: 125 
Abbreviations: CYP = cytochrome P450. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 257 of 259 
APPENDIX B. RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS VERSION 1.1 
Evaluation of Target Lesions 
Evaluation of target lesions will be performed as detailed in Table 58 and below: 
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters. 
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm. (Note: the appearance of ≥1 new lesion is also considered 
progressions). 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 
Evaluation of Non-Target Lesions 
Evaluation of target lesions will be performed as detailed in Table 59 and below: 
Complete Response (CR): Disappearance of all nontarget lesions and normalization of tumor 
marker level. All lymph nodes must be nonpathological in size (<10 mm short axis). 
Note: If tumor markers are initially above the upper normal limit, they must normalize for a 
patient to be considered in complete clinical response. 
Non-CR/Non-PD: Persistence of ≥1 nontarget lesion and/or maintenance of tumor marker level 
above the normal limits. 
Progressive Disease (PD): Appearance of ≥1 new lesion and/or unequivocal progression of 
existing nontarget lesions. Unequivocal progression should not normally trump target lesion 
status. It must be representative of overall disease status change, not a single lesion increase. 
Although a clear progression of “nontarget” lesions only is exceptional, the opinion of the 
treating physician should prevail in such circumstances, and the progression status should be 
confirmed at a later time by the review panel (or Investigator). 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for PD the smallest measurements recorded 
since the treatment started). The patient’s best response assignment will depend on the 
achievement of both measurement and confirmation criteria. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 258 of 259 
Table 58: 
RECIST v1.1 Response for Patients with Measurable Disease (i.e., Target 
Disease) 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
Best Overall Response When 
Confirmation is Requireda 
CR 
CR 
No 
CR 
>4 weeks confirmationb 
CR 
Non-CR/non-PD 
No 
PR 
>4 weeks confirmationb 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/non-PD/not 
evaluated 
No 
PR 
SD 
Non-CR/non-PD/not 
evaluated 
No 
SD 
Documented at least once 
>4 weeks from baselineb 
PD 
Any 
Yes or no 
PD 
No prior SD, PR, or CR 
Any 
PDc 
Yes or no 
PD 
Any 
Any 
Yes 
PD 
Source: 120 
Abbreviations: CR = complete response; PD = progressive disease; PR = partial response; RECIST v1.1 = Response Evaluation 
Criteria in Solid Tumors version 1.1; SD = stable disease. 
Note: Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence of 
disease progression at that time should be reported as “symptomatic deterioration.” Every effort should be made to document 
the objective progression even after discontinuation of treatment. 
a See RECIST v1.1 publication120 for further details on what is evidence of a new lesion. 
b Only for nonrandomized trials with response as primary endpoint. 
c In exceptional circumstances, unequivocal progression in nontarget lesions may be accepted as disease progression. 
 
Table 59: 
RECIST v1.1 Response for Patients With Nonmeasurable Disease 
(i.e., Nontarget Disease) 
Non-target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PDa 
Not all evaluated 
No 
Not evaluated 
Unequivocal PD 
Yes or no 
PD 
Any 
Yes 
PD 
Source: 120 
Abbreviations: CR = complete response; PD = progressive disease; RECIST v1.1 = Response Evaluation Criteria in Solid 
Tumors version 1.1; SD = stable disease. 
a ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for nontarget disease since SD is increasingly used as an endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised. 

Niraparib, TSR-042, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy  
Clinical Study Protocol Study 3000-01-002 Version 3.0 
 
Confidential 
Page 259 of 259 
APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS 
Description 
Grade 
Source: 126 
 
 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.