A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Subjects With Advanced Solid Tumors
Phase: PHASE1
Conditions: Solid Tumors
Sponsor: BeiGene

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Clinical Study Protocol 
Protocol Title:  
A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation 
and Expansion Study to Investigate the Safety, 
Pharmacokinetics and Antitumor Activity of the 
anti-PD-1 
Monoclonal 
Antibody 
BGB-A317 
in 
Combination with the PARP Inhibitor BGB-290 in 
Subjects with Advanced Solid Tumors 
Protocol Number: 
BGB-A317/BGB-290_Study_001 
EudraCT Number: 
2017-003580-35 
Date of Protocol: 
18 September 2018, Version 4 
Study Phase: 
1/1b 
Sponsor: 
BeiGene AUS Pty Ltd.  
c/o Becis Pty Ltd. 
1C/528 Compton Road 
Stretton, Queensland 4116 
Australia  
 
BeiGene, Ltd.  
c/o BeiGene USA, Inc. 
1900 Powell Street, 5th Floor 
Emeryville, CA 94608 
USA  
 
Sponsor Medical Monitor: 
 
 
Coordinating Investigator: 
 
 
 
Confidentiality Statement 
This confidential information in this document is provided to you as an investigator or consultant for review by you, your 
staff, and the applicable Institutional Review Board/Independent Ethics Committee. Your acceptance of this document 
constitutes agreement that you will not disclose the information contained herein to others without written authorization 
from the sponsor. 

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SIGNATURE 
PROTOCOL TITLE: 
A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and 
Expansion Study to Investigate the Safety, Pharmacokinetics 
and Antitumor Activity of the anti-PD-1 Monoclonal Antibody 
BGB-A317 in combination with the PARP inhibitor BGB-290 
in Subjects with Advanced Solid Tumors 
PROTOCOL NO: 
BGB-A317/BGB-290_Study_001 Version 4, dated 18 
September 2018 
 
_______ 
 
 
___________________ 
 
 
 
 
 
Date 
Sponsor Medical Monitor 
 
 
 

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PROTOCOL VERSION 4 - RATIONALE AND CHANGE 
INVENTORY 
The purpose of this amendment is to incorporate the following changes: 
 Updated the number of patients previously treated in the study. 
 Updated Rationale for Dose Selection for Part B. 
 Remove Disease-Specific Cohort for Non-Small Cell Lung Cancer. 
 Added exploring potential predictive biomarkers for resistance to Exploratory 
Objectives. 
 Clarified length of time for Safety Follow-up for AEs and irAEs. 
 Clarified number of patients in Part B. 
 Clarified number of lines of prior treatment a patient received prior to study 
treatment. 
 Added allowance for urine pregnancy test after screening. 
 Added new assessment for CK and CK-MB. 
 Included alcohol consumption assessment. 
 Updated Coagulation Parameters, Thyroid Function, Blood Sample, and Dose 
Modification. 
 Added new section Treatment beyond Progression. 
 Updated description of Investigational Product. 
 Updated Recommended Diagnostic Tests in the Management of Possible Immune-
related Adverse Events 
 Included the International Nonproprietary Name, tislelizumab, in place of ‘BGB-
A317’ and pamiparib, in place of ‘BGB-290’ throughout the protocol. 
 Updated medical monitor. 
 

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SYNOPSIS 
Name of 
Sponsor/Company: 
BeiGene Ltd. 
Name of Finished 
Product and Active 
Ingredients: 
Tislelizumab (BGB-A317) and Pamiparib (BGB-290) 
Title of Study: 
A Phase 1/1b, Open-Label, Multiple-Dose, Dose Escalation and Expansion Study to 
Investigate the Safety, Pharmacokinetics and Antitumor Activity of the anti-PD-1 
Monoclonal Antibody BGB-A317 in combination with the PARP inhibitor BGB-290 
in Subjects with Advanced Solid Tumors 
Protocol No: 
BGB-A317/BGB-290_Study_001 
Study Centers: 
Approximately 30-50 study centers (global participation) 
Study Duration: Screening up to 28 days, Treatment up to 2 years, Safety Follow-up 
up to 30 days, and Survival Follow-up (approximately every 3 months).  
Phase:1/1b 
Objectives: 
Part A (Dose-escalation) 
Primary: 
 
To assess the safety and tolerability of tislelizumab (BGB-A317) in combination with pamiparib 
(BGB-290) 
 
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for the 
combination 
Secondary: 
 
To characterize the pharmacokinetics (PK) of pamiparib and tislelizumab in combination  
 
To assess the preliminary anti-tumor activity of tislelizumab in combination with pamiparib 
 
To assess host immunogenicity to tislelizumab 
Exploratory: 
Part B (Expansion Cohorts) 
Primary: 
 
To assess the preliminary anti-tumor activity of the combination of tislelizumab and pamiparib in 
patients with specific tumor types  
Secondary: 
 
To further assess the safety and tolerability of the combination 
 
To further characterize the PK of tislelizumab and pamiparib in combination 
 
To further assess host immunogenicity to tislelizumab 
Exploratory: 



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Methodology: 
Part A: 
Part A is a multicenter, open-label, multiple-dose, dose-escalation study in patients with advanced solid 
tumors likely to harbor DNA damage repair deficiencies susceptible to treatment with poly (ADP-ribose) 
polymerase (PARP) inhibitor or known to be responsive to programmed cell death-1 (PD-1) blocker. Five 
combination dose levels (DLs) are planned. The study will follow a 3+3 dose-escalation scheme. The dose-
limiting toxicity (DLT) assessments will be evaluated during the first cycle consisting of the first 21 days of 
treatment. The Safety Monitoring Committee (SMC), consisting of investigators, the sponsor’s medical 
delegate, safety delegate, and the contract research organization’s (CRO) medical monitor, will evaluate 
safety data after patients have completed at least one cycle of treatment in order to make a decision on dose-
escalation, and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). 
The SMC may decide to evaluate an intermediate, not pre-defined, previously evaluated or not previously-
evaluated dose or a less frequent dosing schedule that will not exceed the MTD level, if evaluation of toxicity 
at such a dose or schedule is desired. If this approach is taken, up to 6 new patients should be enrolled at that 
dose or schedule. 
Starting dose and dose-escalation rules 
In all dose levels, tislelizumab will be administered as an intravenous (IV) infusion on Day 1 of each 21-day 
cycle, and pamiparib will be taken orally twice daily starting from Day 1. The starting dose for each agent 
and the starting DL of the combination was based on the doses evaluated in the on-going monotherapy dose-
escalation study for each agent and is significantly lower than the highest safe dose that has been identified 
to date. The study will follow a 3+3 dose-escalation scheme at the pre-defined DLs until MTD and/or RP2D 
is determined for the combination. At least 3 patients will be enrolled into each cohort. Additional patient(s), 
up to a maximum of six (6) patients in total, will be enrolled. The DLT assessment and dose-escalation scheme 
will follow the same principle as stipulated for a 3+3 dose escalation design. When a minimum of 2 patients 
experience DLT at a given DL, this DL will be defined as intolerable. The MTD is the DL at which 0/6 or 1/6 
patients experience DLT with at least two patients experiencing DLT at the next higher DL. 
Part B 
Part B will evaluate the safety and tolerability and anti-tumor activity of tislelizumab + pamiparib treatment 
in the arms of specific tumor types defined below. The RP2D is tislelizumab 200 mg IV Q3W + pamiparib 
40 mg orally twice daily. Each arm will enroll approximately 20 patients. All patients must have received 
standard of care in the primary treatment of their disease. Patients with platinum-refractory disease are 
excluded.  Platinum-refractory disease is defined as progressive disease at the time of the first tumor 
assessment while receiving a platinum-containing therapy. Enrollment into these disease-specific cohorts will 
occur simultaneously and independent of each other. 
Arm 1a: Patients with relapsed, platinum-sensitive high grade epithelial, non-mucinous, ovarian cancer, 
fallopian tube, or primary peritoneal cancer (EOC) with either known germline or somatic 
BRCA1/2 mutations or with homologous recombination deficiency (HRD). Patients must have 
received at least 2 prior lines of platinum-containing chemotherapy  
Arm 1b: Patients with relapsed, platinum-sensitive high grade EOC without either known germline or 
somatic BRCA1/2 mutations and without known HRD. Patients must have received at least 2 prior 
lines of platinum-containing chemotherapy. 
Arm 2: Patients with triple negative breast cancer (TNBC) with either known germline or somatic BRCA1/2 
mutations or with documented HRD.  Patients can have been treated with at least 1 but not more 
than 3 prior lines of treatment.   
Arm 3: Patients with metastatic castration-resistant prostate cancer (mCRPC) with either known germline 
or somatic BRCA1/2 mutations or with documented HRD. Chemotherapy-naïve patients must have 
received prior abiraterone acetate or enzalutamide treatment 

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Arm 4: Patients with extensive-stage disease small cell lung cancer (SCLC) treated at least 1 and not more 
than 2 prior lines of treatment; at least 1 regimen must include a platinum agent 
Arm 5: Patients with HER2-negative gastric or gastroesophageal junction cancer.  Patients with HER2-
negative disease may be treated with at least 1 but no more than 2 prior lines of treatment.  
Arm 6: Patients with locally advanced or metastatic urothelial (muscle invasive bladder, ureter, urethra or 
renal pelvis) cancer treated with at least 1 but no more than 2 prior lines of treatment, including a 
prior platinum-containing chemotherapy  
Arm 7: Patients with advanced or metastatic pancreatic adenocarcinoma treated with at least 1 but no more 
than 2 prior lines of treatment. Any potential patient with a known deleterious germline or somatic 
BRCA is eligible even if platinum-naïve 
Arm 8: Patients who may be expected to benefit from the combination of a PARP inhibitor and a PD-1 
inhibitor. This arm will include patients with recurrent non-ovarian gynecological cancers 
(endometrial cancer, cancer of the cervix and patients with tumors known to be mismatch repair 
deficient [MMR] or HRD positive) that are not eligible for inclusion in any other arms of the trial. 
This is an exploratory signal seeking arm and is closed to enrollment. 
 
For Arm 1 (ovarian cancer), Arm 2 (TNBC), and Arm 3 (mCRPC), patients with known eligible mutation 
status can be enrolled into the study if otherwise eligible. Tissue/blood specimens will be collected for a 
confirmatory test. Patients who do not have known germline or somatic BRCA mutation, or known HRD 
status must sign a separate pre-screening informed consent to evaluate HRD status prior to enrollment. 
For Arm 1 (EOC), Arm 1a may be analyzed independently of Arm 1b. All Arms will enroll up to 40 patients. 
Arm 8 is closed to enrollment. 
Fresh blood samples will be collected at baseline and at defined times as indicated for all patients in Part B 
for the evaluation of germline mutations, which may include BRCA mutations and/or confirmation of prior 
BRCA results or other homologous recombination deficiency mutations. All patients enrolled in Part B must 
submit archival tumor tissue, unless previously discussed with sponsor’s medical monitor or its designee. A 
fresh biopsy of an accessible tumor lesion is required at baseline (within 12 weeks of starting treatment) in 
the absence of archival tumor tissue, unless previously discussed with the sponsor’s medical monitor or its 
designee. Optional tumor biopsies will also be obtained in consenting patients to evaluate the 
pharmacodynamic effects and resistance mechanisms.  
Part A and Part B 
Patients will be monitored for safety, tolerability, anti-tislelizumab antibodies, and anti-tumor activity 
throughout the study from the day of first administration of study drugs up to 30 days following last study 
treatment or initiation of new anticancer therapy, whichever occurs first. Radiological assessment of tumor 
response should be performed approximately every 9 ± 1 weeks in the first year and approximately every 
12 ± 1 weeks thereafter. 
Tumor response will be assessed by investigators based on Response Evaluation Criteria in Solid Tumors 
(RECIST) Version 1.1. For patients with ovarian, fallopian tube, or primary peritoneal cancer, investigators 
may also incorporate GCIG CA-125 response criteria with RECIST Version 1.1 response criteria in assessing 
tumor response. For patients with prostate cancer, Prostate Cancer Clinical Trials Working Group 3 (PCWG3) 
criteria will also be used to evaluate prostate-specific antigen (PSA) and modified RECIST responses.  
Accumulating evidence indicates some patients treated with immunotherapy may derive clinical benefit 
despite initial evidence of progressive disease (PD). Patients will be permitted to continue study treatment 
beyond initial RECIST v1.1 defined PD for the time periods below and if they meet the following criteria: 
 
Investigator-assessed clinical benefit  
 
Patient is tolerating study drug and agrees to continued study treatment 

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 
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Protocol Appendix 3) 
 
Absence of rapid progression of disease or of progressive tumor at critical anatomical sites (eg, cord 
compression) that necessitates urgent alternative medical intervention 
 
Patients must be reconsented to continue study treatment beyond disease progression. 
For suspected pseudo-progression, treatment may continue until confirmation of PD with repeat imaging at 
least 4 weeks later or at the next regularly scheduled imaging time point, but not more than 12 weeks from 
the initial documentation of pseudo-progression.  All decisions to continue treatment beyond initial 
progression must be documented in the medical record, and agreed to by the sponsor medical monitor.  
This study will be considered complete once all patients have manifested disease progression; ceased study 
treatment due to death; exhibit intolerance; withdrawn consent from the study; or completed a total of 2 years 
of treatment. Any patient in this study who continues to demonstrate objective clinical benefit at the end of a 
2-year treatment duration may continue in the study or on treatment. 
Planned Number 
of Patients: 
Part A: Approximately 50 patients for the dose escalation until MTD and/or RP2D 
determination. 
Part B: Up to approximately 200 patients for expansion in arms of specific tumor 
types.  Each Arm will be evaluated independently for study endpoints and can either 
be closed due to suboptimal clinical anti-tumor activity or expanded by enrolling an 
additional 20 patients if sufficient anti-tumor activity (eg, higher objective response 
rate [ORR] or longer progression-free survival [PFS] than expected) is observed.  
Statistical justification of such sample size expansion will be included in the final 
statistical analysis plan as applicable. 
Study Population 
Key inclusion criteria: 
1. Patients have voluntarily agreed to participate by giving written informed 
consent. 
2. Patients must have received standard of care in the primary treatment of their 
disease. 
3. Patients who have the below specified histologically confirmed 
malignancies that have progressed to the advanced or metastatic stage. 
a) In Part A, the patients must have an advanced malignancy including but 
not limited to high-grade serous cancer of the ovary, fallopian tube, or 
peritoneum, triple negative breast cancer, SCLC, primary peritoneal 
cancer, and any tumor likely to harbor DNA damage repair deficiencies 
susceptible to treatment with a PARP inhibitor or likely to be responsive 
to a PD-1 blocker. 
b) In Part B, the patients recruited to one of the eight expansion arms must 
have advanced solid tumors of the following types: 
Arm 1: Patients with relapsed, platinum-sensitive high grade epithelial, non-
mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer 
(EOC) must meet the following criteria: 
i. Patients must have at least 2 prior platinum-containing treatments in 
any treatment setting. 
 Note: patients may have received additional therapy after the 
last platinum-containing regimen if the other eligibility criteria 
are met. 
ii. 
Patients must have platinum-sensitive recurrent disease and must not 
have progressed (by RECIST v1.1 criteria) within 6 months of the 
completion of the last platinum-containing line of treatment.  

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 Note: patients may receive additional non-platinum based 
chemotherapy for recurrence after prior last 
platinum-containing regimen if the criteria for 
platinum-sensitivity are met. 
iii. 
Arm 1a: Patients with relapsed, platinum-sensitive high grade 
epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary 
peritoneal cancer (EOC) with either known deleterious or suspected 
deleterious germline or somatic BRCA1/2 mutations or with HRD.  
 If HRD or BRCA1/2 mutation status from archival tissue is 
unknown or has not been previously evaluated, then the 
archival tissue must undergo tissue screening using a validated 
diagnostic test to determine eligibility. If the diagnostic test 
result is BRCA1/2 or HRD positive the patient will be eligible 
for enrollment in Arm 1a. 
iv. Arm 1b: Patients with relapsed, platinum-sensitive high grade EOC 
who otherwise meet the above criteria and are without known 
germline or somatic BRCA1/2 mutations and without HRD mutation. 
Arm 2: Patients with triple negative breast cancer must meet the following 
criteria: 
i. Patients with 0-1 prior platinum-containing treatment in any 
treatment setting. 
 Note: patients could have received additional therapy after the 
last platinum-containing line of treatment if the other 
eligibility criteria are met. 
ii. 
Patients who have received at least 1 prior treatment but not more 
than 3 prior lines of treatment in the advanced or metastatic setting.  
iii. 
Known deleterious or suspected deleterious germline or somatic 
BRCA1/2 mutations or with documented HRD.  
 If HRD or BRCA1/2 mutation status from archival tissue is 
unknown or has not been previously evaluated, then the 
archival tissue must undergo tissue screening using a validated 
diagnostic test to determine eligibility. If the diagnostic test 
result is HRD positive, then the patient will be eligible for 
enrollment in Arm 2. 
 If archival tissue is not available and the patient submits a 
fresh tumor biopsy, then the diagnostic test needs to 
demonstrate somatic BRCA1/2 mutation or HRD positivity. 
Arm 3: Patients with metastatic castration-resistant prostate cancer, including 
but not limited to mutations in homologous recombination (HR) 
pathways and/or defined by HRD algorithms, and must meet the 
following criteria: 
i. The patient may be either chemotherapy-naïve, but must have 
received prior abiraterone acetate and/or enzalutamide treatment, or 
have previously had no more than 2 taxane-based chemotherapy 
lines of treatment including docetaxel and carbazitaxel. If docetaxel 
is used more than once, this will be considered as 1 line of treatment. 
ii. 
At least 2 weeks since the completion of prior flutamide, 
bicalutamide, and nilutimide, or enzalutamide and abiraterone 
treatment. 
iii. 
Documented prostate cancer with one of the following: 

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 Surgically or medically castrated. The testosterone levels do 
not need to be checked if the patient has undergone surgical 
castration for > 4 months. Patients receiving chemical 
castration should have testosterone levels checked at baseline 
and confirmed to be in the castrate levels (< 0.5 ng/mL or 
1.735 nM). In all cases the luteinizing hormone-releasing 
hormone (LHRH) antagonist/agonist is to be continued in 
these patients. 
 Patients with only non-measurable bone lesions must have 
disease progression based on PCWG3 with 2 or more new 
lesions or have prostate-specific antigen (PSA) progression 
before enrollment. 
iv. Known deleterious or suspected deleterious germline or somatic 
BRCA1/2 mutations or with documented HRD.   
 If HRD or BRCA1/2 mutation status from archival tissue is 
unknown or has not been previously evaluated, then the 
archival tissue must undergo tissue screening using a validated 
diagnostic test to determine eligibility. If the diagnostic test 
result is HRD positive, then the patient will be eligible for 
enrollment in Arm 3. 
 If archival tissue is not available and the patient submits a 
fresh tumor biopsy, then the diagnostic test needs to 
demonstrate somatic BRCA1/2 mutation or HRD positivity. 
Arm 4: Patients with extensive-stage disease small cell lung cancer (SCLC) 
must meet the following criterion: 
i. Patients received at least 1 and not more than 2 prior lines of 
treatment. 
ii. 
At least 1 prior line of treatment must have contained a platinum 
agent 
Arm 5: Patients with HER2-negative gastric or gastroesophageal junction 
cancer must meet the following criteria: 
i. Patients with HER2-negative may have received at least 1 and not 
more than 2 prior lines of treatment. 
Arm 6: Patients with locally advanced or metastatic urothelial (muscle-
invasive bladder, ureter, urethra or renal pelvis) cancer must meet the 
following criteria: 
i. Patients received at least 1 and not more than 2 prior lines of 
treatment in the advanced or metastatic disease setting. 
ii. 
At least 1 prior line of treatment must have contained a platinum 
agent 
Arm 7: Patients with advanced or metastatic pancreatic adenocarcinoma must 
meet the following criteria: 
i. 
Received at least one but not more than 2 lines of treatment in 
either an advanced or metastatic setting; 
ii. 
At least 1 prior treatment for advanced or metastatic disease must 
have contained a platinum agent 

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iii. 
Patients with known deleterious germline or somatic BRCA1/2 
mutation can be considered for the study even if platinum-naive 
Arm 8: (NOTE: CLOSED TO ENROLLMENT) Patients with advanced or 
metastatic recurrent non-ovarian gynecological cancers (endometrial 
cancer, cancer of the cervix and patients with tumors known to be 
MMR deficient or HRD positive) must meet the following criteria: 
i. Patients with a complete response, partial response or stable disease 
from at least 1 prior platinum-containing treatment in any treatment 
setting. 
ii. The Sponsor medical monitor will approve tumor types for Arm 8 
prior to screening. 
 Note: Excluded tumor types include patients with bone or soft 
tissue sarcoma; central nervous system (CNS) malignancies; 
colorectal cancer (except microsatellite instability-high 
[MSI-H] colorectal cancer is permitted); cutaneous or ocular 
melanoma; hematologic malignancies; HER2-negative breast 
cancer without BRCA mutation; mesothelioma, papillary, 
follicular, medullary or Hürthle cell thyroid cancer; unknown 
primary malignancy. 
4. Patients who were treated with chemotherapy or any investigational 
therapies, if eligible, must have been completed at least 4 weeks or at least 
5 half-lives (whichever is longer, but no less than 3 weeks) before the study 
drug administration, and all AEs have either returned to baseline or  
5. At least 2 weeks from palliative radiotherapy. 
6. Patients must have archival tumor tissue or agree to a tumor biopsy for 
mutation and biomarkers analysis unless previously discussed with sponsor’s 
medical monitor or its designee (fresh tumor biopsies are recommended at 
baseline in patients with readily accessible tumor lesions and who consent to 
the biopsies). Patients with ovarian, fallopian tube, primary peritoneal, or 
breast cancer in Part A and all patients enrolled in Part B must also agree to 
provide fresh blood sample at the baseline for the evaluation of BRCA 
mutations and/or confirmation of prior BRCA results or other homologous 
recombination deficiency mutations even if it was previously tested. 
7. Patients must have measurable disease as defined in RECIST v1.1. Patients 
with metastatic castration-resistant prostate cancer and epithelial, non-
mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer may 
use separate disease-specific criteria (Protocol Appendix 4, Appendix 6, and 
Appendix 8). 
8. Patients must be a male or female ≥ 18 years of age on the day of signing 
informed consent. 
9. Patients must have an ECOG Performance Status (PS) ≤ 1 (Protocol 
Appendix 3). 
10. Patients must have a life expectancy ≥ 12 weeks. 
11. Patient must have adequate organ function as indicated by the following 
laboratory values independent of transfusion within 2 weeks: 
a) Absolute neutrophil count (ANC) ≥ 1,500/mL. 
b) Platelets ≥ 100,000/mL. 

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c) Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L.  
d) Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 by 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 
equation (Protocol Appendix 18). 
e) Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) (On 
fractionation ≤ 90% of total bilirubin should be unconjugated. Total 
bilirubin must be < 4 X ULN for patients with Gilbert’s syndrome). 
f) 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase 
[SGOT]) and alanine aminotransferase (serum glutamic pyruvic 
transaminase [SGPT]) ≤ 2.5 × ULN. 
g) International normalized ratio (INR) ≤ 1.5 × ULN (≤ 2.5 × ULN if on 
anticoagulants).  
12. Females of childbearing potential must be willing to use a highly effective 
method of birth control for the duration of the study (Protocol Appendix 17), 
and for at least 6 months after the last dose of investigational drug, and have 
a negative serum pregnancy test within 7 days of the first dose of study 
drug(s). 
13. Non-sterile males and their female partners must be willing to use a highly 
effective method of birth control for the duration of the study and for at least 
6 months after the last dose of investigational drug (Protocol Appendix 17). 
Nonsterile males must avoid sperm donation for the duration of the study and 
for at least 6 months after last study drug.  
14. Female patient must agree not to breastfeed starting at screening and 
throughout the study period, and for 6 months after the final study drug 
administration.  
Key exclusion criteria: 
1. Platinum-resistant/refractory disease, defined as progressive disease at the 
first tumor assessment while receiving platinum-containing chemotherapy  
2. Patient has history of severe hypersensitivity reactions to other monoclonal 
antibodies (mAbs). 
3. Any major surgery within 28 days before first dose of study drugs. 
4. Prior allogeneic stem cell transplantation or organ transplantation. 
5. Patients with toxicities (as a result of prior anticancer therapy) which have 
not recovered to baseline or stabilized, except for AEs not considered a likely 
safety risk (eg, alopecia, neuropathy and specific laboratory abnormalities). 
6. Concurrent participation in another therapeutic clinical trial. 
7. Prior malignancy within the previous 2 years except for locally curable non-
melanoma dermatologic cancers that have been apparently cured, such as 
basal or squamous cell skin cancer, or carcinoma in situ of the skin, cervix, 
breast, bladder, or prostate. 
8. Symptomatic CNS metastasis or leptomeningeal disease. 
Note: Baseline MRI of the brain and spinal cord is required for SCLC patients 
enrolled in Arm 4 if they have a history of CNS disease.  
Note: Patients with previously treated CNS metastatic disease are eligible for 
any arm if CNS metastatic disease is asymptomatic, clinically stable, and does 

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not require corticosteroids or anticonvulsants within a minimum of 4 weeks 
of enrollment. 
9. Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or 
PARP. The exception to this criterion are patients eligible for Arm 9; where 
patients may have received either a PD-1 inhibitor or PD-L1 inhibitor. 
10. Active autoimmune diseases or history of autoimmune diseases that may 
relapse (Protocol Appendix 15).  
Note: Patients with the following diseases are not excluded and may proceed 
to further screening:  
a) Controlled Type I diabetes. 
b) Hypothyroidism managed with no treatment other than with hormone 
replacement therapy. 
c) Controlled celiac disease. 
d) Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, 
alopecia). 
e) Any other disease that is not expected to recur in the absence of external 
triggering factors. 
11. Any condition that required systemic treatment with either corticosteroids 
(> 10 mg daily of prednisone or equivalent) or other immunosuppressive 
medication within 2 weeks of the study drug administration. 
Note: Patients who are currently or have previously been on any of the 
following steroid regimens are not excluded: 
a) Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or 
equivalent).  
b) Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid 
with minimal systemic absorption. 
c) Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, 
for contrast dye allergy) or for the treatment of a non-autoimmune 
condition (eg, delayed-type hypersensitivity reaction caused by contact 
allergen). 
12. With severe chronic or active infections requiring systemic antibacterial, 
antifungal or antiviral therapy, including tuberculosis infection, etc. 
13. History of interstitial lung disease, non-infectious pneumonitis or 
uncontrolled systemic diseases, including diabetes, hypertension, pulmonary 
fibrosis, acute lung diseases, etc. 
14. History of non-viral hepatitis or cirrhosis. 
15. Positive human immunodeficiency virus (HIV) status. 
16. A known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) 
infection. 
17. History of alcohol abuse. 
18. Underlying medical conditions or alcohol or drug abuse or dependence that, 
in the investigator’s opinion, will be unfavorable for the administration of 
study drug or affect the explanation of drug toxicity or adverse events; or 
insufficient compliance during the study according to investigator’s 

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judgement. 
19. Inability to swallow oral medications (capsules and tablets) without chewing, 
breaking, crushing, opening or otherwise altering the product formulation. 
Patients should not have gastrointestinal illnesses that would preclude the 
absorption of pamiparib, which is an oral agent. Please note Protocol 
Appendix 12 for a list of prohibited medications that are associated with 
possible interactions with pamiparib. 
20. Has been administered a live vaccine within 4 weeks (28 days) of initiation 
of study therapy.  Patients are eligible if 28 days have elapsed since receipt 
of vaccine and initiation of study treatment.  (NOTE: seasonal vaccines for 
influenza are generally inactivated vaccines and are allowed.  Intranasal 
vaccines are live vaccines; and are not allowed). 
21. Any of the following cardiovascular criteria: 
a) Current evidence of cardiac ischemia. 
b) Current symptomatic pulmonary embolism. 
c) Acute myocardial infarction ≤ 6 months prior to Day 1. 
d) Heart failure of New York Heart Association Classification III or IV 
(Protocol Appendix 16) ≤ 6 months prior to Day 1. 
e) Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to Day 1. 
f) 
History of cerebrovascular accident within 6 months before first dose of 
study drugs. 
22. Use or have anticipated need for food or drugs known to be strong or 
moderate cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers 
≤ 10 days (or ≤ 5 half-lives, whichever is shorter) prior to Day 1 (Appendix 
12) 
Test Product, Dose 
and Mode of 
Administration: 
Drugs: Combination of tislelizumab and pamiparib 
Tislelizumab will be administered as an IV infusion over 30-60 minutes; once every 
3 weeks (Q3W) (see Protocol Section 6.2 for instructions). 
Pamiparib will be administered orally, twice daily. 
In both Parts A and B of the study, tislelizumab will be administered as an IV infusion 
on Day 1 of a 21-day cycle, and pamiparib will be taken orally twice daily starting 
from Day 1.  
Part A: Proposed Dose levels: 
Level 1: tislelizumab, 2 mg/kg IV Q3W, pamiparib, 20 mg orally twice daily 
Level 2: tislelizumab, 2 mg/kg IV Q3W, pamiparib, 40 mg orally twice daily 
Level 3: tislelizumab, 2 mg/kg IV Q3W, pamiparib, 60 mg orally twice daily 
Level 4: tislelizumab, 200 mg IV Q3W, pamiparib, 40 mg orally twice daily 
Level 5: tislelizumab, 200 mg IV Q3W, pamiparib, 60 mg orally twice daily 
The proposed DLs may be further modified and additional doses may be considered 
based on the safety, tolerability, and efficacy observed during dose escalation, ie, flat 
dose of tislelizumab at 200 mg or 300 mg IV Q3W. An intermediate, not pre-defined, 
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schedule that will not exceed the MTD level, if evaluation of toxicity at such a dose 
or schedule is desired. 
Part B:  
Tislelizumab: 200 mg IV Q3W 
Pamiparib: 40 mg orally twice daily 
This combination will be given until disease progression or other discontinuation 
criteria are met. 
Reference 
Therapy, Dose and 
Mode of 
Administration: 
Not applicable 
Criteria for Evaluation: 
Part A: 
Primary Endpoints: 
 
Safety and tolerability as assessed by the incidence and nature of AEs 
 
Incidence and nature of DLTs  
 
Determination of maximum tolerated dose of the combination of tislelizumab and pamiparib 
Secondary Endpoints: 
 
Pharmacokinetic parameters, including but not limited to Ctrough of tislelizumab and Cmax, Tmax and 
Ctrough of pamiparib 
 
Efficacy parameters including: 
o 
Objective response rate (ORR) is defined as a best overall response of complete response (CR) and 
partial response (PR) 
o 
Disease control rate (DCR) is defined as a best overall response of CR, PR and stable disease (SD) 
o 
Clinical benefit rate (CBR) is defined as a best overall response of CR, PR and SD lasting 
≥ 24 weeks 
o 
PFS is defined as the time from first dose of study medication to the first documented objective 
disease progression or death due to any cause, whichever occurs first 
o 
Overall survival (OS) is defined as the time from the date of first dose of study drug to death due 
to any cause 
 
Immunogenicity of tislelizumab 
Exploratory Endpoints: 
 
Part B: 
Primary Endpoint: 
 
Anti-tumor activity as determined by ORR, PFS, duration of response (DOR), DCR, CBR, and OS 

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Secondary Endpoints: 
 
Safety and tolerability as assessed by the incidence and nature of AEs 
 
Pharmacokinetic parameters, including but not limited to Ctrough of tislelizumab and pamiparib 
 
Immunogenicity of tislelizumab 
 
Statistical Methods: 
Data will be listed and summarized according to the sponsor-agreed reporting standards, where applicable.  
All patients (both parts) who are exposed to (or started receiving) the combination agents will be included in 
the safety analysis set. All patients for whom valid tislelizumab or pamiparib PK parameters can be estimated 
will be included in the PK analysis set on an as-treated basis.  
As described in the objectives, the trial is designed to establish the safety and tolerability of tislelizumab and 
pamiparib combination and to assess the preliminary anti-tumor activity of the combination in selected tumor 
types. No formal hypothesis testing is planned. Descriptive statistical analyses will be performed for all 
patients in the safety analysis set. The safety and efficacy (eg, ORR, PFS, DOR, DCR, CBR and OS) data 
will be presented by part and arm. 
Sample Size: 
Number of patients in Part A will depend on the incidence of DLT reported. Approximately 50 patients are 
expected in Part A of the trial.  
Part B will include expansion arms of specific tumor types.  Up to approximately 40 patients per cohort may 
be enrolled.  The purpose of these expansion arms is to explore signals of clinical efficacy as well as to 
confirm the safety and tolerability of the combination in each selected tumor type. Anti-tumor activity will be 
evaluated in Part B. A decision can be made to stop an arm early due to suboptimal clinical anti-tumor activity.  
Up to a total of 40 patients may be enrolled in any disease cohort to evaluate the anti-tumor activity if evidence 
of activity is observed in the first 20 patients enrolled. 
The probability of observing at least one responder is approximately 88% in an expansion arm (n = 20) when 
the underlying ORR is as low as 10%. 
 

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TABLE OF CONTENTS 
Contents 
SIGNATURE ............................................................................................................................2 
PROTOCOL VERSION 4 - RATIONALE AND CHANGE INVENTORY .....................3 
SYNOPSIS ................................................................................................................................4 
TABLE OF CONTENTS ......................................................................................................16 
LIST OF TABLES .................................................................................................................21 
LIST OF FIGURES ...............................................................................................................21 
1.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................22 
2.0 
INTRODUCTION......................................................................................................28 
2.1 
Background and Pharmacology ...................................................................28 
2.1.1 
Tislelizumab ......................................................................................28 
2.1.2 
Pamiparib ...........................................................................................29 
2.1.3 
Tislelizumab and Pamiparib combination .........................................30 
2.2 
Overview of Clinical Pharmacology .............................................................32 
2.2.1 
Tislelizumab ......................................................................................32 
2.2.2 
Pamiparib ...........................................................................................32 
2.3 
Overview of Safety and Efficacy ...................................................................33 
2.3.1 
BGB-A317 Study-001 .......................................................................33 
2.3.2 
Pamiparib ...........................................................................................35 
2.4 
Benefit-Risk Assessment ................................................................................39 
2.5 
Study Rationale ..............................................................................................40 
2.5.1 
Rationale for Dose Selection .............................................................40 
2.5.2 
Rationale for Disease-Specific Cohorts (Phase 1B) ..........................41 
3.0 
STUDY OBJECTIVES ..............................................................................................48 
3.1 
Part A (Dose Escalation) ...............................................................................48 
3.1.1 
Primary Objectives ............................................................................48 
3.1.2 
Secondary Objectives ........................................................................48 
3.1.3 
Exploratory Objectives ......................................................................48 
3.2 
Part B (Expansion Cohorts) ..........................................................................48 
3.2.1 
Primary Objectives ............................................................................48 
3.2.2 
Secondary Objectives ........................................................................48 
3.2.3 
Exploratory Objectives ......................................................................48 
4.0 
STUDY ENDPOINTS ................................................................................................49 
4.1 
Part A (Dose Escalation) ...............................................................................49 
4.1.1 
Primary Endpoints .............................................................................49 
4.1.2 
Secondary Endpoints .........................................................................49 
4.1.3 
Exploratory Endpoints .......................................................................49 
4.2 
Part B (Expansion Cohorts) ..........................................................................50 
4.2.1 
Primary Endpoints .............................................................................50 

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4.2.2 
Secondary Endpoints .........................................................................50 
4.2.3 
Exploratory Endpoints .......................................................................50 
5.0 
INVESTIGATIONAL PLAN ...................................................................................51 
5.1 
Summary of Study Design .............................................................................51 
5.1.1 
Part A: Dose Escalation and Dose Finding .......................................55 
5.1.2 
Part B: Expansion ..............................................................................56 
5.1.3 
Schedule of Assessments ...................................................................58 
5.1.4 
Dose Modifications, Dose Delay, and Missing Dose ........................76 
5.1.5 
Treatment beyond Progression ..........................................................78 
5.2 
Selection of Study Population .......................................................................78 
5.2.1 
Inclusion Criteria ...............................................................................78 
5.2.2 
Exclusion Criteria ..............................................................................83 
5.2.3 
Other Eligibility Criteria Considerations ...........................................85 
5.2.4 
Patient Restrictions ............................................................................86 
5.2.5 
Patient Discontinuation and Withdrawal ...........................................86 
6.0 
STUDY TREATMENTS ...........................................................................................88 
6.1 
Description of Investigational Product ........................................................88 
6.2 
Dosage and Administration ...........................................................................88 
6.3 
Patient Identification .....................................................................................89 
6.4 
Packaging and Labeling ................................................................................89 
6.5 
Handling and Storage ....................................................................................90 
6.6 
Product Accountability ..................................................................................90 
6.7 
Assessment of Compliance ............................................................................91 
6.8 
Treatment of Investigational Product Overdose .........................................91 
6.9 
Medical Care of Patients after the End of Trial..........................................91 
6.10 
Occupational Safety .......................................................................................91 
7.0 
CONCOMITANT MEDICATIONS AND NON-DRUG THERAPIES ...............92 
7.1 
Permitted Medications...................................................................................92 
7.2 
Prohibited Medications .................................................................................92 
7.2.1 
Other Study Considerations ...............................................................93 
8.0 
STUDY ASSESSMENTS ..........................................................................................94 
8.1 
Prescreening (Part B Only) ...........................................................................94 
8.2 
Screening .........................................................................................................94 
8.2.1 
Demographic and Baseline Assessments ..........................................95 
8.2.2 
Females of Childbearing Potential and Contraception ......................97 
8.3 
Assessments During Treatment ....................................................................97 
8.3.1 
Laboratory Evaluation .......................................................................97 
8.3.2 
Physical Examination, Ophthalmologic Examinations 
and Vital Signs ..................................................................................98 
8.3.3 
Medical History/ Prior Medications ..................................................99 
8.3.4 
Electrocardiogram .............................................................................99 
8.3.5 
Serum Tumor Markers ....................................................................100 
8.3.6 
Computed Tomography ...................................................................101 
8.3.7 
Optional Tumor Biopsy ...................................................................103 

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8.3.8 
Adverse Events ................................................................................103 
8.4 
Safety Assessments .......................................................................................103 
8.4.1 
Safety Evaluation .............................................................................104 
8.5 
Follow-up Assessments ................................................................................105 
8.6 
Visit Windows...............................................................................................106 
8.7 
Unscheduled Visits .......................................................................................106 
8.8 
Efficacy Assessment .....................................................................................107 
8.8.1 
Disease Progression and Treatment beyond Disease 
Progression ......................................................................................107 
8.9 
Pharmacokinetics .........................................................................................108 
8.9.1 
Blood Sample Collection and Handling ..........................................109 
8.10 
Anti-Drug Antibody .....................................................................................109 
8.11 
Biomarker Assessments ...............................................................................110 
8.12 
Appropriateness of Measurements .............................................................111 
9.0 
QUALITY CONTROL AND QUALITY ASSURANCE .....................................112 
9.1 
Monitoring ....................................................................................................112 
9.2 
Data Management/Coding ..........................................................................113 
9.3 
Quality Assurance Audit .............................................................................114 
10.0 
SAFETY MONITORING AND REPORTING ....................................................116 
10.1 
Risks Associated with Tislelizumab ...........................................................116 
10.2 
General Plan to Manage Safety Concerns .................................................116 
10.2.1 
Eligibility Criteria ............................................................................116 
10.2.2 
Safety Monitoring Plan ....................................................................116 
10.3 
Adverse Events .............................................................................................117 
10.3.1 
Definition and Reporting of an Adverse Event ...............................117 
10.4 
Definition of a Serious Adverse Event .......................................................120 
10.5 
Timing, Frequency, and Method of Capturing Adverse Events 
and Serious Adverse Events ........................................................................121 
10.5.1 
Adverse Event Reporting Period .....................................................121 
10.5.2 
Eliciting Adverse Events .................................................................122 
10.6 
Specific Instructions for Recording Adverse Events and 
Serious Adverse Events ...............................................................................122 
10.6.1 
Disease Progression .........................................................................122 
10.6.2 
Death ................................................................................................122 
10.7 
Suspected Unexpected Serious Adverse Reaction .....................................122 
10.8 
Prompt Reporting of Serious Adverse Events...........................................123 
10.8.1 
Timeframes for Submitting Serious Adverse Events ......................123 
10.8.2 
Completion and Transmission of the Serious Adverse 
Event Report ....................................................................................123 
10.8.3 
Regulatory Reporting Requirements for Serious Adverse 
Events ..............................................................................................123 
10.9 
Pregnancy Reporting ...................................................................................124 
10.10 Post-study Adverse Event............................................................................124 
10.11 Assessing and Recording Immune-Related Adverse Events ....................124 

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10.12 Expedited Reporting to Health Authorities, Ethics Committees 
and Investigators ..........................................................................................125 
10.13 Special Precautions ......................................................................................125 
10.13.1 Tumor Lysis Syndrome ...................................................................125 
10.13.2 Infusion-Related Reaction ...............................................................127 
10.13.3 Severe Hypersensitivity Reactions and Flu-Like 
Symptoms 128 
10.13.4 Immune-Related Adverse Events (irAE) .........................................129 
10.13.5 Renal Function Abnormalities .........................................................130 
11.0 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ........................131 
11.1 
Sample Size Considerations ........................................................................131 
11.2 
General Considerations for Data Analysis ................................................131 
11.2.1 
Analysis Populations .......................................................................132 
11.2.2 
Data Analysis ...................................................................................133 
11.2.3 
Patient Disposition ...........................................................................133 
11.2.4 
Demographic and Other Baseline Characteristics ...........................133 
11.2.5 
Prior and Concomitant Medication .................................................133 
11.3 
Efficacy Analyses .........................................................................................133 
11.4 
Safety Analyses .............................................................................................134 
11.4.1 
Dose Limited Toxicity .....................................................................134 
11.4.2 
Maximum Tolerated Dose ...............................................................134 
11.4.3 
Adverse Events ................................................................................135 
11.4.4 
Laboratory Assessments ..................................................................135 
11.4.5 
Electrocardiogram ...........................................................................135 
11.4.6 
Vital Signs .......................................................................................136 
11.4.7 
Extent of Exposure ..........................................................................136 
11.4.8 
Physical Examination ......................................................................136 
11.4.9 
Ophthalmologic Examination ..........................................................136 
11.5 
Pharmacokinetic Analyses ..........................................................................136 
11.6 
Biomarker Analyses .....................................................................................137 
12.0 
ETHICS ....................................................................................................................138 
12.1 
Regulatory Authority Approval .................................................................138 
12.2 
Ethical Conduct of the Study and Ethics Approval ..................................138 
12.3 
Informed Consent ........................................................................................138 
12.4 
Handling of Clinically Significant Findings of Genomic 
Studies ...........................................................................................................139 
12.5 
Investigator Reporting Requirements........................................................140 
13.0 
STUDY ADMINISTRATION ................................................................................141 
13.1 
Study and Study Center Closure ................................................................141 
13.2 
Records Retention ........................................................................................141 
13.3 
Provision of Study Results and Information to Investigators ..................143 
13.4 
Information Disclosure and Inventions .....................................................143 
13.4.1 
Publication and Data Sharing Policy ...............................................144 
14.0 
REFERENCES .........................................................................................................145 

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15.0 
APPENDICES ..........................................................................................................153 
APPENDIX 1: SIGNATURE OF INVESTIGATOR .......................................................153 
APPENDIX 2: CLINICAL LABORATORY ASSESSMENTS ......................................154 
APPENDIX 3: EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS ...................................................................................155 
APPENDIX 4: EVALUATION OF RESPONSE ACCORDING TO CA-125 ...............156 
APPENDIX 5: EVIDENCE OF PROGRESSIVE DISEASE TO DETERMINE TRIAL 
ENTRY ELIGIBILITY IN PATIENTS WITH PROSTATE CANCER ...........158 
APPENDIX 6: PROSTATE CANCER CLINICAL TRIALS WORKING GROUP 3 
(PCWG3) CRITERIA TO GUIDE ASCRIBING DISEASE RESPONSE .........160 
APPENDIX 7: DRUG DILUTION CALCULATION FOR BGB-A317 ........................162 
APPENDIX 8: THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
(RECIST) GUIDELINES ........................................................................................163 
APPENDIX 9: GUIDELINES FOR SUPPORTIVE CARE ............................................173 
APPENDIX 10: IMMUNE-RELATED ADVERSE EVENTS MANAGEMENT 
GUIDANCE FOR INVESTIGATORS ..................................................................175 
APPENDIX 11: CRITERIA FOR INTERRUPTION AND RE-INITIATION OF 
PAMIPARIB ............................................................................................................187 
APPENDIX 12: PROHIBITED MEDICATIONS (STRONG AND MODERATE 
CYP3A INHIBITORS AND STRONG CYP3A INDUCERS ..............................191 
APPENDIX 13: MEDICATIONS TO BE USED WITH CAUTION (SENSITIVE 
CYP2C9 SUBSTRATES OR CYP2C9 SUBSTRATES WITH NARROW 
THERAPEUTIC INDEX) .......................................................................................192 
APPENDIX 14: MEDICATIONS TO BE USED WITH CAUTION (STRONG CYP2C8 
INHIBITORS) ..........................................................................................................193 
APPENDIX 15: PRE-EXISITING IMMUNE DEFICIENCIES OR AUTOIMMUNE 
DISEASES ................................................................................................................194 
APPENDIX 16: NEW YORK HEART ASSOCIATION CLASSIFICATION .............195 
APPENDIX 17: CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL”, “NO CHILDBEARING 
POTENTIAL” ..........................................................................................................196 
APPENDIX 18: CHRONIC KIDNEY DISEASE EPIDEMIOLOGY 
COLLABORATION EQUATION .........................................................................198 
 
 

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LIST OF TABLES 
 
Table 1: Suggested Dose-Escalation Scheme ..........................................................................55 
Table 2: Dose-limiting Toxicity Assessment Criteria .............................................................56 
Table 3: Part A; All Dose Levels: Study Assessments and Procedures Schedule ...................59 
Table 4: Part A; All Dose Levels: Pharmacokinetic Sampling ................................................65 
Table 5: Part B: Study Assessments and Procedures Schedule ...............................................67 
Table 6: Part B: Pharmacokinetic/ADA Sampling1 .................................................................74 
Table 7: Time Frame for Reporting Serious Adverse Events to the Sponsor or 
Designee ..................................................................................................................123 
Table 8: Treatment Modification for Symptoms of Infusion-Related Reactions 
Due to Study Drug(s) ...............................................................................................127 
Table 9: Immune-Related Adverse Events ............................................................................129 
 
LIST OF FIGURES 
Figure 1: Overall Study Design (Part A; All Dose Levels) .....................................................53 
Figure 2: Overall Study Design (Part B1) ................................................................................54 
Figure 3: Assessment and Initial Management of Tumor Lysis Syndrome...........................126 
 

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1.0 LIST OF ABBREVIATIONS AND DEFINITIONS OF 
TERMS 
Abbreviation 
Definition 
ADA 
anti-drug antibody 
ADP 
adenosine diphosphate 
AE 
adverse event 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ASAP 
as soon as possible 
AST 
aspartate aminotransferase 
ATM 
Ataxia-Telangiectasia Mutated 
AUC 
area under the plasma concentration-time curve 
BGB-290 
code name for PARP inhibitor; pamiparib 
BGB-A317 
code name for monoclonal antibody BGB-A317; tislelizumab 
BRCA1/2 
breast cancer type 1/2 susceptibility gene 
C1q 
complement 1q, a subunit of complement 1 
CA-125 
carcinoma antigen 125 
CBC 
complete blood count 
CBR 
clinical benefit rate 
CD 
cluster of differentiation, such as CD274, CD279, and CD3 
CDC 
complement-dependent cytotoxicity 
CEA 
carcinoembryonic antigen 
CNA 
circulating nucleic acids 
CNS 
central nervous system 
CR 
complete response 
CRC 
colorectal cancer 
CRF 
case report form 
CRO 
contract research organization 
CT 
computed tomography 
Ctrough 
minimum observed plasma concentration 

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CYP 
cytochrome P450 
DBP 
diastolic blood pressure 
DCR 
disease control rate 
DDI 
drug-drug interaction 
DL 
dose level 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGRF 
estimated glomerular filtration rate 
EGFR 
epidermal growth factor receptor 
ENR 
Enrolled set 
EOC 
high grade epithelial, non-mucinous ovarian, fallopian tube or 
primary peritoneal cancer 
Fab 
fragment antigen-binding 
Fc 
fragment crystallizable region (typically, of immunoglobulin G) 
FcγR 
gamma Fc receptor, such as Fc RI, and Fc RIII 
FDA 
Food and Drug Administration 
FDG 
Fluorodeoxyglucose 
FDG-PET 
PET scanning with the tracer fluorine-18 [F-18] FDG 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony-stimulating factor 
GM-CSF 
granulocyte macrophage colony-stimulating factor 
GMP 
Good Manufacturing Practice 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HGSOC 
high-grade serous ovarian cancer 
HIV 
human immunodeficiency virus 

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HNSCC 
head and neck squamous cell carcinoma 
HR 
homologous recombination 
HRD 
homologous recombination deficiency 
IB 
Investigator’s Brochure 
IC50 
inhibitory concentration for 50% of maximal activity 
ICF 
informed consent form 
ICU 
Intensive Care Unit 
ID 
Identification 
IEC 
Independent Ethics Committee 
IFN-α 
interferon alpha 
IFN-γ 
interferon gamma 
IgG 
immunoglobulin G, such as IgG1, IgG2, IgG3 and IgG4; other 
types of immunoglobulins include IgM and IgD 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IPI 
Ipilumumab 
irAEs 
immune-related adverse events 
IRB 
Institutional Review Board 
ITP 
idiopathic thrombocytopenic purpura 
IV 
Intravenous 
KD 
dissociation constant 
LFT 
liver function tests 
mAbs 
monoclonal antibodies 
MAD 
maximum administered dose 
(m)CRPC 
(metastatic) castration-resistant prostate cancer 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
N 
Number 
NCI 
National Cancer Institute 

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NCI-CTCAE 
National Cancer Institute’s Common Terminology Criteria for 
Adverse Events 
NE 
not evaluable 
NK 
natural killer cells 
NSAID 
nonsteroidal anti-inflammatory drug 
NSCLC 
non-small cell lung cancer 
ORR 
objective response rate 
OS 
overall survival 
OTC 
over-the-counter 
pamiparib 
BGB-290 
PAR 
poly (ADP-ribose) 
PARP 
poly (ADP-ribose) polymerase 
PARPi 
poly (ADP-ribose) polymerase inhibitors 
PBMC 
peripheral blood mononuclear cell 
PCWG3 
Prostate Cancer Clinical Trials Working Group 3 
PD 
progressive disease 
PD-1 
programmed cell death-1 
PD-L1 
programmed death-ligand 1, programed death receptor ligand-1, 
Programed Death-1 Ligand-1 
PD-L2 
program death ligand-2 
PDX 
patient-derived xenograft 
PET 
positron emission tomography 
PFS 
progression-free survival 
pH 
negative of the logarithm to base 10 of the activity of the 
(solvated) hydronium ion 
PK 
Pharmacokinetics 
PKS 
pharmacokinetic analysis set 
PR 
partial response 
PS 
performance status 
PSA 
prostate-specific antigen 
PT 
prothrombin time 
Q2W 
once every 2 weeks 

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Q3W 
once every 3 weeks 
QT 
QT interval of the electrocardiogram 
QTc 
QT interval corrected for heart rate 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RP2D 
recommended Phase 2 dose 
SAEs 
serious adverse events 
SAF 
safety analysis set 
SBP 
systolic blood pressure 
SCC 
squamous cell carcinoma 
SCLC 
small cell lung cancer 
SCr 
serum creatinine concentration 
SD 
stable disease 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SLE 
systemic lupus erythematosus 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
SOP 
standard operating procedure 
SPR 
surface plasmon resonance 
t1/2 
half-life 
T3 
Triiodothyronine 
T4 
Thyroxine 
TCGA 
The Cancer Genome Atlas 
TCR 
T-cell receptor 
TEAE 
treatment emergent adverse event 
TILs 
tumor-infiltrating lymphocytes 
Tislelizumab 
BGB-A317 
TLS 
Tumor Lysis Syndrome 
Tmax 
time to reach maximum plasma concentration 
TNBC 
triple negative breast cancer 

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TSH 
thyroid-stimulating hormone 
UK 
United Kingdom 
ULN 
upper limit of normal 
US 
United States 
Vd 
volume of distribution 
WBC 
white blood cell 
WHO-DD 
World Health Organization Drug Dictionary Enhanced 
β-HCG 
β-subunit of human chorionic gonadotropin 
 

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2.0 INTRODUCTION 
2.1 
Background and Pharmacology 
The immune check point-inhibitory receptor, programmed cell death-1 (PD-1) is mainly 
expressed in activated T-cells including cluster of differentiation (CD)8+ cytotoxic T-
lymphocytes and CD4+ T-helper lymphocytes. [1] It is believed that PD-1 plays an important 
role in immune modulation of tumor progression by regulating the key inhibitory signaling in 
the T-cells when engaged by its ligands. The PD-1 signaling cascade negatively regulates T-
cell receptor (TCR) and attenuates T-cell proliferation and functional activities, leading to T-
cell exhaustion. PD-1 expression is markedly up-regulated in tumor-infiltrating lymphocytes 
(TILs), while the expression of PD-1 ligand (PD-L1) is significantly increased in tumor cells 
and tumor-associated immune cells in the presence of stimulating cytokines such as interferon 
gamma (IFN-γ) and interferon alpha (IFN-α) in the tumor microenvironment. [2] Furthermore, 
the increased PD-1 expression in TILs and/or PD-L1 expression in tumor and tumor-associated 
stromal cells is observed in many types of solid human tumors including, but not limited to, 
melanoma, squamous cell carcinoma (SCC), uveal melanoma, non-small cell lung cancer 
(NSCLC), head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer 
(TNBC), renal cell carcinoma (RCC), bladder cancer, ovarian cancer, and prostate cancer. 
[3-11] These findings provide the basis for cancer immunotherapeutic intervention via the 
approach of antagonizing PD-1. 
Recent clinical trials utilizing anti-PD-1 monoclonal antibodies demonstrated significant 
therapeutic efficacy in advanced melanoma, refractory NSCLC, and RCC. Nivolumab 
(OPDIVO) has 7 Food and Drug Administration (FDA) approved indications: unresectable or 
metastatic melanoma, metastatic NSCLC, RCC, classical Hodgkin lymphoma, and SCC of the 
head and neck, and advanced urothelial cancer. Pembrolizumab (KEYTRUDA) has 4 FDA-
approved indications: unresectable or metastatic melanoma, metastatic NSCLC, recurrent or 
metastatic HNSCC, and refractory classical Hodgkin lymphoma in both pediatric and adults. 
Atezolizumab (TECENTRIQ) has 2 FDA-approved indications: advanced urothelial cancer 
and metastatic NSCLC. 
2.1.1 Tislelizumab 
Tislelizumab is a humanized IgG4-variant monoclonal antibody against PD-1. Tislelizumab 
has been manufactured under Good Manufacturing Practice (GMP) quality control systems. 
The clinical trial drug product is formulated in an aqueous buffer with pH 6.5 and isotonic 
osmolality. The suggested administration route is intravenous (IV) infusion after the 
appropriate dilution in 0.9% sodium chloride solution. 
Tislelizumab binds to the extracellular domain of human PD-1 with high specificity and 
affinity (KD = 0.15 nM) as demonstrated by the receptor-binding assays based on surface 

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plasmon resonance (SPR). It competitively blocks the binding of both PD-L1 and PD-L2, 
inhibiting PD-1-mediated negative signaling in T-cells. In in vitro cell-based assays, the 
humanized antibody consistently and dose-dependently enhances the functional activity of 
human T-cells and pre-activated, primary PBMCs (peripheral blood mononuclear cells). In 
addition, tislelizumab demonstrated anti-tumor activity in several human cancer allogeneic 
xenograft models, including A431 human epidermoid carcinoma, BCCO-028 colon cancer, 
and BCLU-054 NSCLC models, where the PBMCs were co-injected with the human cancer 
cells (A431) or the tumor fragments (BCCO-028 and BCLU-054) into the 
immunocompromised mice. 
The IgG4-variant antibody has very low binding affinity to Fcγ RIIIA and C1q by in vitro 
assays, suggesting a low or no antibody-dependent cellular cytotoxicity and complement-
dependent cytotoxicity (CDC) effect in humans. Unlike the natural IgG4 antibody, tislelizumab 
has no observable Fab-Arm Exchange activity by the in vitro assay, predicting the antibody 
would be stable in vivo, unlikely forming a bispecific antibody. 
Refer to the Investigator’s Brochure (IB) for more detailed information on the background of 
tislelizumab. [12] 
2.1.2 Pamiparib 
Poly (ADP-ribose) polymerase (PARP) proteins are involved in deoxyribonucleic acid (DNA) 
replication, transcriptional regulation, and DNA damage repair. DNA-bound PARP1/2 
catalyzes the synthesis of poly (ADP-ribose) (PAR) onto a range of DNA-associated proteins 
that mediate DNA repair. PARP1 also undergoes auto-PARylation, a molecular change that 
ultimately leads to its release from DNA. Inhibition of PARP converts common single-strand 
DNA breaks (SSBs) into double-strand breaks during DNA replication. Small-molecule 
inhibitors of PARP1/2 represent a class of anticancer agents that exert their cytotoxic effects 
by interfering with DNA repair mechanisms. Since the discovery of synthetic lethality of 
PARP inhibitors in BRCA-deficient cells and, more broadly, cells with homologous 
recombination deficiency (HRD), accumulation of unrepaired SSBs resulting from catalytic 
PARP inhibition has been considered central to the mechanism of action of PARP inhibitors. 
More recently, it has been demonstrated that PARP inhibitors also trap PARP1- and PARP2-
DNA complexes at DNA damage sites and that PARP trapping can be more cytotoxic than 
unrepaired SSBs. 
Recent data supports the evaluation of PARP inhibitors in solid tumors carrying mutations in 
BRCA1 and BRCA2. Mutations of BRCA1 and BRCA2, two tumor suppressor genes, predispose 
cells to increased risk of malignancies, particularly breast and ovarian cancer. Mutations in 
BRCA1 and BRCA2 were identified in up to 10% of pancreas adenocarcinoma patients with a 
higher incidence in those who had a family history. [13, 14] Recent sequencing data indicates 

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that approximately 20% of mCRPC have homologous recombination (HR) defects due to 
germline and /or somatic loss of function in key HR genes including BRCA2, ATM, CHEK2, 
NSBP1, and FANCJ, that could potentially confer a ‘BRCA-like’ phenotype and susceptibility 
to PARP inhibition via synthetic lethality. [15-18] 
In the clinic, PARP inhibitors (olaparib, rucaparib, niraparib, and talazoparib) have 
demonstrated sustained anti-tumor responses as a single agent in patients with BRCA1- or 
BRCA2-mutant tumors, with an acceptable safety profile.  
Pamiparib is a potent and selective inhibitor of PARP1 and PARP2. Single agent pamiparib 
demonstrated excellent in vivo anti-tumor activity, 16-fold more potent than olaparib, in 
MDA-MB-436 
breast 
cancer 
(BRCA1 
mutation) 
xenograft 
model. 
In 
pharmacokinetic/pharmacodynamic study, oral administration of pamiparib resulted in 
time-dependent and dose-dependent inhibition of PARylation in MDA-MB-436 breast cancer 
xenografts in mice. Inhibition of PARylation in the tumor tissues correlated well with tumor 
drug concentrations of pamiparib. 
In combination studies, pamiparib and paclitaxel in combination showed better anti-tumor 
activity than either single agent in primary gastric cancer model. In primary SCLC model, 
pamiparib significantly enhanced the anti-tumor activity of chemotherapy (etoposide plus 
carboplatin) during the concomitant treatment stage, and kept animals tumor-free throughout 
the maintenance treatment.  
Refer to the IB for more detailed information on the background of pamiparib. [19]  
2.1.3 Tislelizumab and Pamiparib combination 
This study will investigate the safety, PK, and anti-tumor activity of the combination 
tislelizumab and pamiparib in patients with tumors likely to harbor DNA damage repair 
deficiencies and which have already shown responsiveness to checkpoint inhibition. This trial 
will evaluate the hypothesis that pamiparib treatment in these susceptible tumors may lead to 
the release of neo-antigens and increase the antigenicity of tumors, which may boost the 
efficacy of tislelizumab.   
There are several reports describing a direct link between DNA damage and immune response. 
[20, 21] The DNA damage response alerts the innate immune system by inducing the 
expression of ligands for activating the immune receptor NKG2D. NKG2D plays an important 
role in the natural killer (NK) and T-cell-mediated immune response to tumors. [22] In 
addition, the specific killing of BRCA mutant or HRD tumor cells by PARP inhibitors can lead 
to release of neo-antigen and immune activation against the tumor, as demonstrated in 
preclinical experiments in both ovarian and breast cancers, supporting investigating the 
combination of a PARP inhibitor and a PD-1 inhibitor.  

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An in vitro study on murine epithelial ovarian cancer cell line reported that administration of 
modest amounts of talazoparib, a potent PARP-1 inhibitor belonging to the same class as 
pamiparib, significantly improved the survival of mice bearing subcutaneous or intraperitoneal 
tumors. [23] Talazoparib was found to have signiﬁcantly increased the number of peritoneal 
CD8+ T cells and natural killer (NK) cells, as well as their production of IFN-γ and tumor 
necrosis factor alpha (TNF-α). The cell stress caused by talazoparib induced not only cancer 
cell-intrinsic apoptosis but also cancer cell-extrinsic anti-tumor immune effects in a syngeneic 
murine model of ovarian cancer. [23] These changes may enhance the anti-tumor immune 
response and lead to synergy of antitumor activity between a PARP inhibitor and anti-PD-1 
antibodies.  
Homologous recombination deficient high grade serous ovarian cancers, including BRCA1/2-
mutated tumors, exhibit higher neo-antigen load compared to HR proficient tumors. In the 
Cancer Genome Atlas (TCGA) dataset, BRCA1/2-mutated tumors were associated with a 
higher ratio of CD8+/CD4+ in tumor-infiltrating lymphocytes (TILs), higher peri-tumoral T-
cells, and increased PD-L1 expression. [24] These characteristics have been associated with 
better responses to anti-PD-1/PD-L1 immune checkpoint inhibitors. Furthermore, a recent 
study using breast cancer cell lines, xenograft and syngeneic tumors provided evidence for 
cross talk between PARP inhibition and tumor-associated immunosuppression. PARP 
inhibition upregulates tumor cell PD-L1 expression, which attenuates PARPi efficacy via PD-
1/PD-L1 signaling associated immunosuppression. [25] The blockade of PD-L1 can restore 
the attenuated anti-tumor immunity and potentiate PARPi in tumor suppression. The efﬁcacy 
of PD-1 pathway blockade correlates with DNA repair pathway mutations and neo-antigen 
burden. [26] In conclusion, platinum-sensitive tumors that are known to respond to PARP 
inhibitors are likely to show enhanced sensitivity to the combination of PARP inhibitor and 
anti-PD-1 therapy. 
Clinical trials investigating the safety and efficacy of a PARP inhibitor in combination with a 
PD-1 or a PD-L1 inhibitor are ongoing (ClinicalTrials.gov Identifiers: NCT02657889; 
NCT02849496; NCT02734004; NCT02484404). Results from a Phase 1 study of durvalumab 
combined with olaparib are available (ClinicalTrials.gov Identifier: NCT02484404). [27] 
Grade 3 or higher adverse events were reported as lymphopenia in 2 of 12 treated patients and 
anemia in one patient. The recommended Phase 2 dose (RP2D) in this study was determined 
to be olaparib 300 mg twice daily with 1500 mg durvalumab IV every 28 days. The preliminary 
data from the BGB-A317/BGB-290_Study_001 and the data published by Lee, et al suggest 
that the checkpoint inhibitor + PARP inhibitor combination has an acceptable toxicity profile. 
[27] 
The selection of disease-specific cohorts in Phase 1B is based on pathologic subtypes that may 
be associated with endogenous loss of DNA damage repair or exogenous DNA damage. 

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Endogenous mutational damage and exogenous DNA damage may limit cancer cells’ capacity 
to carry out DNA repair making cancer cells susceptible to PARP inhibition. Moreover, high 
somatic nonsynonymous mutation burden has been associated with clinical efficacy of PD-1 
inhibition. [28] The combination of pamiparib and tislelizumab may exploit the potential 
accumulation of DNA damage from PARP inhibition, which in turn may increase infiltration 
of immune cells into the tumor microenvironment, thereby increasing cancer cell killing. 
Section 2.5.2 describes each pathology in detail. 
2.2 
Overview of Clinical Pharmacology 
2.2.1 Tislelizumab 
The first-in-human study BGB-A317_001 is a 2-part study: Part A is a dose escalation 
evaluation and Part 2 is a schedule expansion evaluation. One hundred and three patients 
received at least one dose of tislelizumab in the Phase 1A part of the study, ranging from 
0.5 mg/kg to 10 mg/kg Q2W (n = 62) and from 2 mg/kg to 5 mg/kg Q3W (n = 41). The 
maximum tolerated dose (MTD) was not reached and 10 mg/kg Q2W was the maximum 
administered dose (MAD). The RP2D was determined to 200 mg IV Q3W for the Phase 1B 
(indication expansion) study.  
An interim PK analysis (with a cutoff date of 08 October 2016) was conducted by non-
compartmental analysis methods, using serum concentrations from patients who received 
doses of 0.5, 2, 5 and 10 mg/kg Q2W and patients who received doses of 2 and 5 mg/kg Q3W 
(Phase 1a Part 1 and Part 2). The maximum observed plasma concentration (Cmax) and the drug 
exposure (the area under the concentration-time curve [AUC]) increased in a nearly dose-
proportional manner from 0.5 mg/kg to 10 mg /kg, both after single-dose administration and 
at steady state. Population PK analysis was conducted with a 2-compartment model with first 
order elimination. Systemic clearance of tislelizumab was 0.00794 L/h, volume of distribution 
in the central and peripheral compartment were 2.75 and 1.65 L, respectively, and terminal 
elimination half-life was approximately 17 days. Clear drug accumulation was observed after 
multiple doses 
Refer to the IB for more detailed information on the background of tislelizumab. [12] 
2.2.2 Pamiparib 
By 08 April 2016, the dose escalation phase of the BGB-290-AU-002 study had completed. 
Doses at 2.5, 5, 10, 20, 40, 60, 80 and 120 mg twice daily have been evaluated in 45 patients. 
The MTD and RP2D were determined to be 80 mg twice daily and 60 mg twice daily, 
respectively. In the Phase 1 study, interim PK data of pamiparib showed that pamiparib is 
rapidly absorbed and eliminated after oral administration. The Cmax and the drug exposure 
(AUC) increased in a nearly dose-proportional manner from 2.5 mg twice daily to 120 mg 

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twice daily both after the single dose administration and at the steady state. The terminal half-
life was determined to be approximately 13 hours, with a range of 5.5 to 34 hours. At the steady 
state, from 2.5 mg twice daily to 120 mg twice daily, drug exposure was increased in dose-
dependent manner. At 80 mg twice daily (MTD), mean steady state AUC0-24h was 78,348 
ng/ml*h and mean Cmax was 4,881 ng/ml. Refer to the IB for more detailed information on the 
background of pamiparib. [19] 
2.3 
Overview of Safety and Efficacy 
2.3.1 BGB-A317 Study-001 
2.3.1.1 Study BGB-A317_Study_001 Phase 1a 
As of 13 January 2017, 111 patients with solid tumors have been treated with tislelizumab in 
Study BGB-A317_Study_001 for Parts 1, 2, and 3 combined. Patients had received 
tislelizumab treatment in Phase 1a at dose regimens including: 0.5 mg/kg, 2 mg/kg, 5 mg/kg, 
or 10 mg/kg Q2W; 2 mg/kg or 5 mg/kg Q3W; and 200 mg Q3W. The median duration of 
treatment for the combined patient population was 85 days (range: 1 to 471).  
As of 13 January 2017, an MTD has not been determined.  The RP2D was established as fixed 
dose of 200 mg IV Q3W.  
The fixed dose of 200 mg was selected on the basis of both nonclinical studies and available 
clinical data. Simulations do not suggest any clinically meaningful differences in exposure 
following fixed dose or dose adjusted for weight. On the basis of this analysis, a fixed dose of 
200 mg was selected (equivalent to a body weight−based dose of 3.3 mg/kg, calculated with 
60 kg). Selection of an every-21-day dosing interval is both supported by this preliminary 
pharmacokinetics evaluation and allows for a convenient integration with common 
chemotherapeutic regimens. All available PK, safety, and efficacy data for tislelizumab will 
continue to be evaluated to support the 200 mg fixed dose.  
Of the 111 patients in the Safety Analysis set for Phase 1a of Study BGB-A317_Study_001, 
110 (99%) experienced at least 1 treatment emergent adverse event (TEAE). The most 
commonly occurring TEAEs for patients treated with the tislelizumab monotherapy in Study 
BGB-A317_Study _001 were fatigue (42%), nausea (31%), diarrhoea (24%), abdominal pain 
(21%), constipation (21%), back pain (18%), and decreased appetite (18%). TEAEs assessed 
as ≥ Grade 3 were experienced in 45 patients (41%). Grade 3 or higher TEAEs occurring in 
more than 3 patients included abdominal pain (6 patients, 5%), anaemia (5 patients, 5%), back 
pain (4 patients, 4%) and fatigue (4 patients, 4%). 
Treatment-emergent AEs assessed as related to tislelizumab by the Investigator occurred in 
72% of patients across all parts of Phase 1a. Adverse events that occurred in at least 10% of 
patients assessed as related to tislelizumab included fatigue (23%), pruritus (13%), diarrhoea 

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(13%), rash (12%), and nausea (10%). Twelve patients (11%) had at least 1 TEAE assessed as 
related to tislelizumab that were ≥ Grade 3 in severity. These included colitis (n = 1), 
autoimmune pancreatitis (n = 1), fatigue (n = 2), back pain (n = 1), alanine aminotransferase 
increased (n = 1), diabetes mellitus (n = 1), diabetic ketoacidosis (n = 2), hyperglycemia 
(n = 1), pneumonitis (n = 1), hypotension (n = 2). Some patients experienced more than one ≥ 
Grade 3 TEAE that was considered related to tislelizumab. 
Forty-six patients (41%) had a treatment-emergent serious AE (TESAE). The most frequently 
occurring TESAEs included abdominal pain (5 patients, 5%), colitis (4 patients, 4%), and 
ascites, dyspnea, pneumothorax, and pulmonary embolism (3 patients each, 3%). 
In the overall safety population available for analysis, 14 patients (13%) experienced a TEAE 
that led to treatment discontinuation. The most frequently occurring TEAEs leading to 
treatment discontinuation included dyspnoea (2%), pneumonitis (2%), and anaemia (2%). All 
other TEAEs that led to treatment discontinuation occurred in single patients. Of these TEAEs 
that led to treatment discontinuation, 8 (7%) were Grade 3 or greater in severity. The only 
TEAE leading to treatment discontinuation ≥ Grade 3 in severity that occurred in more than 
1 patient was dyspnoea (2 patients, 2%).  
In the overall safety population, 22 patients (20%) experienced a treatment-emergent immune-
related adverse event (irAE). The most frequently occurring irAEs included colitis (4 patients, 
4%), diarrhoea (3 patients, 3%), hypothyroidism (3 patients, 3%), and diabetes mellitus, 
diabetic ketoacidosis, and pneumonitis (2 patients each, 2%). All other irAEs occurred in single 
patients. 
Five patients (5%) experienced a Grade 3 or Grade 4 irAE. These events included colitis 
(n = 1), diarrhea (n = 1), diabetes mellitus (n = 1), diabetic ketoacidosis (n = 2), pneumonitis 
(n = 1), autoimmune pancreatitis (n = 1), type 1 diabetes mellitus (n = 1). These toxicities are 
similar to those reported for other checkpoint inhibitors targeting PD-1 or PD-L1. 
As of 13 January 2017, there were 3 patients had a TEAE with a fatal outcome. The associated 
PTs for these events were fatigue, multi-organ failure, and dyspnoea. None of the TEAEs with 
a fatal outcome were considered related to tislelizumab treatment. 
Of the 111 patients enrolled to the Phase 1a study, 14 patients (13%) achieved a partial 
response and 21 patients had a best response of stable disease.  
2.3.1.2 Study BGB-A317_Study_001 Phase 1b 
As of 13 January 2017, 189 patients with solid tumors had received tislelizumab treatment in 
Phase 1b across 9 expansion cohorts in Study BGB-A317_Study_001. The median duration of 
treatment for the combined patient population was 64 days (range: 1 to 235). The most 
commonly occurring TEAEs were fatigue (22%), nausea (18%), decreased appetite (14%), 

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vomiting (14%), diarrhoea (13%), and constipation (12%). Grade 3 or higher TEAEs occurring 
in more than 3 patients included vomiting (n = 5), pneumonia (n = 5) anaemia (n = 4), and 
ascites (n = 4). 
Treatment-emergent AEs assessed as related to tislelizumab reported ≥ 5% of patients included 
fatigue (9%), rash (5%), nausea (5%), and diarrhoea (5%). Eleven patients experienced 
≥ Grade 3 TEAEs related to tislelizumab. These events included nausea (n = 1), diarrhea 
(n = 2), colitis (n = 2), stomatitis (n = 1), fatigue (n = 1), mucosal inflammation (n = 1), 
pneumonitis (n = 3), and hyperthyroidism (n = 1). Some patients experienced more than one 
≥ Grade 3 TEAE considered related to tislelizumab.   
Twenty patients (11%) experienced a TEAE that led to treatment discontinuation; Grade 3 or 
higher TEAE were reported in 18 of these 20 patients. TEAEs leading to treatment 
discontinuation reported in at least 2 patients included pneumonitis (n = 3) and vomiting 
(n = 2). All other TEAEs that led to treatment discontinuation occurred in single patients. 
Nineteen patients (10%) experienced an irAE. The most frequently occurring irAEs included 
pneumonitis (n = 4); aspartate aminotransferase increased, hyperthyroidism, and rash 
(3 patients each); and colitis, dermatitis, diarrhoea, and hypothyroidism (2 patients each). All 
other irAEs occurred in single patients. Eight of these 19 patients experienced a ≥ Grade 3 
irAE.  
Preliminary efficacy results indicate 6 patients achieved confirmed partial response to 
tislelizumab monotherapy and 55 patients had stable disease.  
2.3.2 Pamiparib 
Pamiparib as a monotherapy is being evaluated in two Phase 1a studies (BGB-290-AU-002 in 
Australia, n = 53 [as of 30 September 2016] and BGB-290-102 in China, n = 8 [as of 13 March 
2017]. The study data from BGB-290-AU-002 is the most mature and key interim results are 
summarized below. 
2.3.2.1 Clinical Safety and Preliminary Efficacy for BGB-290-AU-002 
BGB-290-AU-002 is a first-in-human trial evaluating pamiparib to characterize the safety, the 
MTD, preliminary anti-tumor activity and the PK of pamiparib given as a monotherapy in a 
3+3 dose escalation scheme. Pamiparib was administered in doses ranging from 2.5 mg orally 
twice daily up to 120 mg orally twice daily. 
The study is being conducted in 5 Australian study centers, and preliminary data for 45 patients 
of Part 1A are available (cut-off date of 30 September 2016).  
The median age of enrolled patients was 58 years (range 37 to 74 years), 82% were female 
(n = 37) and 84% white (n = 38). The baseline Eastern Cooperative Oncology Group (ECOG) 

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performance status score, available for 45 patients, was 0 for 16 patients, 1 for 28 patients, and 
2 for one patient. The median of prior systemic anticancer therapies was 3 (range 1 to 9). Most 
common cancer types were gynecologic cancer (n = 28; ovarian, fallopian tube, or primary 
peritoneal), followed by breast cancer (n = 4), lung cancer (n = 4 [n = 3 small cell, n = 1 non-
small cell]), prostate cancer (n = 2) and one each of adenocarcinoma (not otherwise specified), 
leiomyosarcoma, gastroesophageal junction cancer, and uterine cancer. The disease under 
study was not available for 4 patients. 
The pharmacokinetic profile of pamiparib indicates linear PK parameters with a half-life of 
13 hours. A dose-dependent trend in PAR inhibition in PBMCs was seen from 2.5 mg to 10 mg 
twice daily, and was sustained at steady state at doses ≥ 10 mg twice daily. 
The preliminary safety data indicates the most frequent AEs (≥ 10% of patients) assessed as 
related to pamiparib were nausea (51%, n = 23), fatigue (29%, n = 13), vomiting (18%, n = 8), 
diarrhea (16%, n = 7), and decreased appetite (11%, n = 5). Twenty-six patients experienced 
Grade 3 AEs (regardless of relatedness), and no Grade 4 AEs were reported. Eleven Grade 3 
AEs in 9 patients (20%) were considered related to pamiparib: anemia (11%, n = 5), 
neutropenia (7%, n = 3), hypophosphatemia (2%, n = 1), paresthesia (2%, n = 1), nausea (2%, 
n = 1) and fatigue (2%, n = 1).  
Hematologic AEs are of interest in this study. The most frequent hematologic AEs (≥ 10% of 
patients) assessed as related to pamiparib were anemia (22%, n = 10) and neutropenia (11%, 
n = 5). Hematologic AEs, regardless of relatedness, were reported in 40% of patients (n = 18). 
Anemia was most frequent (33%, n = 15), followed by neutropenia (11%, n = 5) and 
thrombocytopenia (2%, n = 1). 
Serious AEs were reported in 25 patients, and for 3 patients they were considered related to 
pamiparib: anemia (n = 2) and nausea (n = 1). Three patients discontinued study drug because 
of an AE: vomiting (n = 1), oral paresthesia (n = 1), and right neck cutaneous metastases 
(n = 1). 
Four patients experienced fatal AEs ≤ 28 days after the last pamiparib dose. All deaths were 
due to complications of the underlying malignancy, and none were considered related to 
pamiparib. 
Four patients experienced AEs that were considered DLTs: experienced Grade 2 nausea that 
persisted despite optimal standard medical therapy in 2 patients; Grade 2 anorexia and Grade 2 
nausea in one patient, and Grade 2 nausea and Grade 2 paresthesia in one patient. Based on the 
encountered DLTs and the overall safety profile of pamiparib, the maximum tolerated dose of 
pamiparib was determined to be 80 mg orally twice daily (160 mg/day). The pamiparib dose 
for further investigation in this study was determined to be 60 mg orally twice daily. 

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Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are recognized adverse 
events in patients receiving PARP inhibitors. [29] To date, no cases of either MDS or AML 
have been observed in any study that includes pamiparib. 
Ten patients achieved either a complete (n = 2) or partial (n = 8) response; all responses were 
observed in patients with gynecological cancers in this ongoing study. 
2.3.2.2 Clinical Update of BGB-A317/BGB-290_Study_001 
As of 05 February 2018, a total of 49 patients were treated in five dose level (DL), as detailed 
below:  
 DL 1:  tislelizumab 2 mg/kg IV Q3W + pamiparib 20 mg orally twice daily (n = 12) 
 DL 2: tislelizumab 2 mg/kg IV Q3W + pamiparib 40 mg orally twice daily (n = 12) 
 DL 3: tislelizumab 2 mg/kg IV Q3W + pamiparib 60 mg orally twice daily (n = 6) 
 DL 4: tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily (n = 7)  
 DL 5: tislelizumab 200 mg IV Q3W + pamiparib 60 mg orally twice daily (n = 4) 
Patients enrolled in the study have a variety of solid tumors, including ovarian (n = 20), 
fallopian tube (n = 4), pancreatic (n = 3), prostate (n = 3), fallopian tube and ovarian (n = 1), 
breast (n = 2), bile duct (n = 1), bladder (n = 1), cervical (n = 1), lung (n = 1), peripheral nerve 
sheath tumor (n = 1), peritoneal (n = 1) and uterine cancer (n = 1).  
Twenty-four patients discontinued one or both study drugs. Among these 24 patients, 
20 patients discontinued the treatment due to either radiographic or clinical disease 
progression. Four patients discontinued tislelizumab due to treatment related adverse events: 
autoimmune hepatitis or elevated liver function tests (n = 3) and immune-related hypophysitis 
(n = 1). Of note, DLTs were defined only for the first cycle and, as these events occurred after 
the first cycle, they were not considered DLTs.   
2.3.2.3 Overview of Safety 
The most commonly reported (> 10 % of the patients) treatment emergent adverse events 
regardless of the relationship were nausea (61%), fatigue (43.9%), vomiting (29.3%), diarrhea 
(26.8%), anemia (19.5%), headache (19.5%), constipation (17.1%), pyrexia (14.6%), urinary 
tract 
infection 
(14.6%), 
alanine 
aminotransferase 
increased 
(12.2%), 
aspartate 
aminotransferase increased (12.2%), back pain (12.2%), cough (12.2%), gastro-oesophageal 
reflux disease (12.2%). Treatment emergent adverse events regardless of the relationship that 
were Grade ≥ 3 and reported in > 5% patients were anemia (7.3%), and gamma-glutamyl 
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The most commonly reported (> 10% of the patients) treatment emergent adverse event that 
was considered related to both pamiparib and tislelizumab was fatigue (31.7%: 26.8% as Grade 
1, and 2.4% each for Grade 2 and Grade 3), and nausea (12.2%: 9.8% as Grade 1 and 2.4% as 
Grade 2). 
One dose limiting toxicity of Grade 2 persistent nausea was reported in a patient treated in 
DL 4. Pamiparib was dose reduced to 20 mg twice daily and the patient continued combination 
treatment until radiographic disease progression approximately 4 weeks later. 
After the data extraction, 2 additional dose-limiting toxicities were reported in DL 5. Dose-
limiting toxicities in DL 5 were Grade 2 persistent nausea and Grade 4 auto-immune hepatitis. 
Study treatment was discontinued in both patients. 
Pamiparib 60 mg twice daily/tislelizumab 200 mg Q3W was considered to be over MTD in 
this combination regimen. Dose Level 4, pamiparib 40 mg twice daily/tislelizumab 200 mg 
Q3W, is being further expanded. 
Immune-related adverse events were reported in 10 patients (24.4%). Events that were reported 
in 2 or more patients were elevated ALT (one each for Grade 1 and Grade 3), elevated AST 
(one each for Grade 1 and Grade 2), autoimmune hepatitis (one each for Grade 3 and Grade 
4), elevated GGT (one each for Grade 2 and Grade 3), and hypothyroidism (two for Grade 1 
and one for Grade 2). Immune-related adverse events that lead to tislelizumab discontinuation 
occurred in 5 patients: Grade 4 autoimmune hepatitis (n = 1), Grade 3 autoimmune hepatitis 
(n = 1), Grade 2 elevated AST and ALT (n = 1), Grade 3 hypophysitis (n = 1) and Grade 3 
hepatitis (n = 1). 
As of 10 April 2017, 12 of 43 patients treated with the combination of tislelizumab and 
pamiparib experienced increases in liver function tests that were reported as adverse events of 
either elevated AST, ALT, hepatitis or auto-immune hepatitis. These events were clinically 
asymptomatic, and were characterized by a proportionally higher increase in alanine 
aminotransferase (ALT) compared to aspartate aminotransferase (AST). No significant 
changes in bilirubin were observed. These hepatic adverse events were observed in all dosing 
cohorts. The median time to onset was 49 days (range 18 to 202 days).  The severity of these 
events was Grade 1 (n = 1), Grade 2 (n = 5), Grade 3 (n = 4), and Grade 4 (n = 2). Two patients 
(one Grade 1 event, one Grade 2 event) did not receive corticosteroid treatment and continued 
study treatment with both agents without consequence. For the remaining 10 patients, 
tislelizumab was discontinued or held. Three of these 10 patients had objective evidence of 
disease progression at the same time of the hepatic adverse events. Progressive disease did not 
seem to correlate with elevated liver function tests, and was not consistently associated with 
new liver metastases nor increases in existing liver metastases. tislelizumab was discontinued 
in 6 out of the 12 patients for hepatic adverse events and is being held in one patient. Pamiparib 

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treatment was continued in 3 patients, and permanently discontinued in 5 patients for 
progressive disease (n = 3) or the hepatic adverse event (n = 2). Four patients were re-
challenged with pamiparib (one patient was re-challenged twice) following corticosteroid 
treatment and all 4 patients experienced liver function tests (LFT) increases with reinstatement 
of pamiparib. Of these 4 patients, 2 discontinued treatment, and 2 were able to continue 
pamiparib after additional corticosteroid treatment at the same or a reduced dose of pamiparib.  
Fourteen patients had at least one SAE reported, only auto-immune hepatitis and hypophysitis 
(one event each and as above) were considered related to treatment. 
There were 5 patients who died within 30 days of the last dose of study drug administration, 
all of which were associated with disease progression. 
2.3.2.4 Preliminary Anti-tumor activity 
Preliminary anti-tumor data suggests that the combination of pamiparib +tislelizumab results 
in tumor shrinkage. One complete response was reported in a patient with ovarian cancer; 
7 patients achieved a partial response (ovarian cancer n = 5; pancreatic cancer n = 1; uterine 
cancer n = 1). 
2.4 
Benefit-Risk Assessment 
Tislelizumab and pamiparib are the investigational products with safety data gathered from 
non-clinical and Phase 1 clinical studies, as described above. The emerging data supports an 
acceptable safety profile of each agent given as monotherapy. The preliminary safety data 
generated in the dose-escalation portion of this ongoing study indicates that the pamiparib + 
tislelizumab can be co-administered in the doses tested.  
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been reported in 
a small number (< 1%) of patients treated with PARP inhibitors, especially in patients 
harboring a germline BRCA mutation. [29] Patients who develop MDS and AML while on 
PARPi therapy typically had a history of extensive previous chemotherapy which is a 
recognized risk for MDS and AML. Patients in this study will be monitored monthly for 
hematological toxicities and reports of MDS and AML will be reported as serious adverse 
events (SAEs). 
Preliminary Phase 1 study data with durvalumab (MEDI4736) given concurrently with 
olaparib supports the tolerability of a PARP + PD-L1 combination similar the treatment being 
investigated in this study. [27] Patients enrolled in clinical studies using the tislelizumab and 
pamiparib combination will continue to be closely monitored by means of reporting AEs, 
recording vital signs and electrocardiograms (ECGs), and conducting clinical laboratory safety 
tests of blood and urine with particular attention paid to the safety profile of what is currently 

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known about both of these compounds as well as what is known about the therapeutic classes 
of both checkpoint and PARP inhibitors. 
2.5 
Study Rationale 
This is a 2-staged, Phase 1/1b study consisting of two parts, to evaluate the combined use of 
tislelizumab and pamiparib. Part A of this study will evaluate safety and tolerability to 
determine the MTD and RP2D for the combination as well as whether the administration of 
pamiparib given for 7 days prior to the initiation of tislelizumab as a means to upregulate neo-
antigen and PD-L1 production will be both tolerable and associated with anti-tumor activity. 
The PK profile, possibility of any potential drug-drug interaction (DDI), preliminary anti-
tumor activity of the combination, as well as host immunogenicity to tislelizumab will also be 
studied. Part B of this study will further evaluate the anti-tumor activity of the combination, its 
safety and PK profile, as well as host immunogenicity to tislelizumab. Preliminary biomarkers 
for efficacy will also be explored through both parts of the study. 
The study population used for both Parts A and B of this study are patients with tumors likely 
to harbor DNA damage repair deficiencies susceptible to treatment with PARP inhibitor or in 
tumor types, which have already shown responsiveness to PD-1 blockade. It is postulated that 
pamiparib treatment in these susceptible tumors may lead to the release of neoantigens that 
could boost the efficacy of tislelizumab, as discussed in Section 2.1.3. 
2.5.1 Rationale for Dose Selection 
Tislelizumab and pamiparib have demonstrated an acceptable toxicology and safety 
pharmacology profile individually, in clinical and non-clinical experiments. In preclinical 
mouse MTD studies, the combination of pamiparib and an anti-mouse PD-1 antibody was very 
well-tolerated without any apparent toxicity compared to either single agent. 
The starting dose of pamiparib was selected as 20 mg twice daily, 1/4 of the monotherapy 
MTD dose (80 mg twice daily) that has been deemed to be safe in the on-going Phase 1 dose-
escalation study. For tislelizumab, 2 mg/kg Q3W was selected as starting dose based on the 
efficacy and PK profile, which is significantly lower than the MAD tested, 10 mg/kg Q2W, in 
the single agent dose-escalation study.  
The dose of each agent tested in the Phase 1B portion of the study was based on the totality of 
the safety data generated in the dose-escalation portion of the trial. The dose of pamiparib 
chosen for the disease-specific expansion cohorts was based on the number of dose-limiting 
toxicities observed across the dosing cohorts. Two dose-limiting toxicities (Grade 2 nausea 
that could not be managed with standard anti-emetic treatments, and Grade 4 auto-immune 
hepatitis; occurring in one patient each) were reported in the Dose Level 5 cohort (pamiparib 
60 mg orally twice daily + tislelizumab 200 mg IV Q3W). The fixed dose of tislelizumab 

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200 mg Q3W was selected on the basis of available clinical data as outlined in Section 2.3.1.1. 
Based on these findings, the Safety Monitoring Committee for this study recommended the 
pamiparib 40 mg orally twice daily + tislelizumab 200 mg IV Q3W dosing be implemented 
for the disease-specific expansion cohorts in Part B of the study. 
2.5.2 Rationale for Disease-Specific Cohorts (Phase 1B) 
2.5.2.1 Ovarian Cancer  
There are data to indicate that HRD status predicts response to PARP inhibition in patients 
with high grade epithelial, non-mucinous ovarian, fallopian tube or primary peritoneal cancer 
(EOC), which includes but may not be restricted to patients with germline or somatic BRCA1/2 
mutations. Published data with FDA-approved PARP inhibitors, olaparib, rucaparib, and 
niraparib, support the efficacy of this approach to treat selected patients with HRD tumors. 
The rationale to treat patients with EOC whose cancer tests negative for BRCA1/2 mutation or 
those without HRD is based on data generated in the NOVA study, which evaluated niraparib 
vs placebo when given in the maintenance setting to patients with platinum-sensitive, recurrent 
ovarian cancer. [30] In this study of 553 enrolled patients, niraparib significantly improved the 
duration of progression-free survival over placebo in patients whose ovarian cancers tested 
positive for a germline BRCA mutation (median PFS 21 vs 5.5 months; HR 0.27; 95% CI 0.07-
0.41), in those with HRD positive (median PFS 12.9 vs 3.8 months; HR 0.38; 95% CI 0.24-
0.59) and in those with no germline BRCA mutation or HRD (median PFS 9.3 vs 3.9 months; 
HR 0.45; 95% CI 0.34-0.61). 
There is a strong rationale to evaluate checkpoint inhibition in patients with ovarian cancer.  
First, high expression of PD-L1 in ovarian cancer is associated with lower 5-year survival rate 
(52.6%) relative to low PD-L1 expressing ovarian tumors (80.2%), suggesting that suppression 
of PD-1 pathway may be associated with clinical benefit. [4] Second, preclinical experiments 
in syngeneic ovarian cancer murine models show tumor regression with PD-1/PD-L1 
blockade. [31] Third, there are several immune checkpoint inhibitors being evaluated in 
clinical trials in ovarian cancer, many of which have reported disease stability and tumor 
shrinkage in patients with recurrent epithelial ovarian cancer. [32] There are ongoing clinical 
trials, including three Phase 3 trials, that are evaluating immune checkpoint inhibitors across 
both platinum-sensitive and platinum-resistant epithelial ovarian cancer patients.  
The current data with the ongoing Phase 1 clinical trial BGB-A317/BGB-290_Study_001 has 
generated preliminary data supporting both the safety and anti-tumor activity of this 
combination. There are other ongoing clinical trials in patients with recurrent ovarian cancer 
in which a PARP inhibitor will be combined with an immune checkpoint inhibitor. 
(ClinicalTrials.gov 
Identifiers: 
NCT02484404, 
NCT02485990, 
NCT02571725, 
and 
NCT02657889). 

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2.5.2.2 Breast Cancer 
BRCA mutations in TNBC are predictive for response to platinum compounds, which has been 
demonstrated in both in vitro experiments and in clinical trials. [33, 34] The TNT trial [35] 
reported that in unselected patients with metastatic triple negative breast cancer, the response 
rates were similar with either carboplatin or docetaxel. However, patients with BRCA1/2 
mutations had a significantly higher response and a longer progression-free survival with 
carboplatin compared to docetaxel treatment. Additionally, a Phase 1 trial of olaparib 
combined with paclitaxel demonstrated clinical activity in patients with TNBC, but was 
complicated by higher than expected rates of neutropenia. [36] 
BRCA mutation status is also predictive for response to PARP inhibitors in TNBC. [36-39] 
Evidence of clinical activity has been observed in all PARP inhibitors (olaparib, niraparib, 
veliparib, rucaparib, and talazoparib) in early phase clinical trials evidenced by overall 
response rates as high as 71% and clinical benefit rates as high as 86% in patients with TNBC 
testing positive for BRCA1/2 mutation. Multiple clinical studies investigating PARP inhibitors 
in patients with BRCA1/2 mutated breast cancer are on-going in both the adjuvant and 
metastatic treatment settings either as single agents or in combination with targeted agents or 
standard chemotherapy regimens. [40] 
There are also preliminary data supporting the role of immune checkpoint inhibitors in TNBC. 
[41] TNBC has a high mutational frequency and an increased concentration of tumor-
infiltrating lymphocytes, presence of CD8+ infiltrates, and high FOXP3 infiltrates, relative to 
other breast cancer subtypes, findings that support treatment with an immune-modulating 
agent. 
Two 
checkpoint 
inhibitors, 
pembrolizumab 
(ClinicalTrials.gov 
Identifier: 
NCT02447003) and atezolizumab (ClinicalTrials.gov Identifier: NCT01375842), have 
published data supporting the efficacy of such an approach in women with heavily pretreated 
metastatic TNBC, with overall response rates of 18.5% and 24%, respectively. 
In summary, both PARP inhibitors and checkpoint inhibitors when given as monotherapies 
have demonstrated preliminary evidence of anti-tumor activity in patients with advanced 
TNBC, thereby supporting the evaluation of the combination of pamiparib with tislelizumab. 
2.5.2.3 Metastatic Castration-Resistant Prostate Cancer  
There is a strong rationale to target DNA repair deficiencies in patients with castration-resistant 
prostate cancer (CRPC). The prevalence of germline or somatic mutations in genes key to 
DNA damage repair pathways is approximately 19% in patients with CRPC, suggesting that 
there is a population of patients who could be identified for targeted therapy, such as PARP 
inhibitors. The recently reported TOPARP trial showed that the incidence of DNA repair 
defects in unselected patients with mCRPC was 32%. Intriguingly, the incidence of BRCA2 
and ATM mutations in this unselected cohort was 16% and the response rate in this subset that 

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was identified to have an underlying HR defect was more than 80% using a composite measure 
of response. [16] Others reported germline gene variants associated with increased risk of 
prostate cancer and underlying homologous recombination deficiency (HRD) include BRCA1, 
MSH5, MUTYH, PMS2, RAD51B, and BRIP1. [15, 17, 18, 42] Patients with germline BRCA1/2 
mutation carriers have a higher risk of nodal or distant metastases and poorer overall survival 
in prostate cancer than non-carriers. [43] 
Furthermore, the results of clinical trials evaluating oral PARP inhibitors such as olaparib, 
niraparib and rucaparib in patients with CRPC demonstrate significant activity and support 
further development of agents targeting DNA repair pathways. [44] 
Translational studies of T-cell infiltration in the prostate gland suggest a role for 
immunotherapy as a therapeutic strategy for prostate cancer. [45] Tumor tissue from men 
treated with anti-androgen therapy was evaluated for lymphocyte markers and cytokines. Anti-
androgen therapy was associated with prominent T-cell infiltration in both epithelial tissue and 
at the tumor site, a finding that was hypothesized to be potentially synergistic with ipilimumab, 
a monoclonal antibody against CTLA-4. While early clinical trial results suggested promise 
with ipilimumab treatment for prostate cancer patients [46], a Phase 3 trial evaluating 
ipilimumab in men with CRPC who had failed docetaxel and were receiving bone-directed 
radiation therapy failed to demonstrate improvement in overall survival relative to a placebo 
control. [47] 
PD-L1 expression both at the tumor cell membrane and in the cytoplasm has been associated 
with poor prognosis in men with prostate cancer and may be an independent prognostic 
indicator of biochemical recurrence. [48] It follows that treatment with an immune checkpoint 
inhibitor combined with PARP inhibition may have therapeutic value in men with mCRPC. 
2.5.2.4 Small Cell Lung Cancer  
Small cell lung cancer (SCLC) constitutes about 15% of newly diagnosed lung cancer cases 
and occurs predominantly in cigarette smokers. [49] SCLC is an aggressive disease treated 
most commonly with platinum-based chemotherapy. Approximately 50% of SCLC patients 
have brain metastases at the time of postmortem examination. Overall survival is typically 
< 12 months. [50]  
SCLC is characterized by its high mutational load, including defects in DNA repair genes. [51, 
52] Several lines of evidence support the evaluation of pamiparib in SCLC. First, PARP 
inhibition with pamiparib was shown to enhance DNA damaging effects of temozolomide in 
both sensitive and resistant SCLC cell lines. Second, pamiparib has demonstrated anti-tumor 
activity in several SCLC patient-derived xenograft (PDX) models when given with 
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carboplatin/etoposide. Finally, preclinical data support pamiparib activity in intracranial 
models of central nervous system (CNS) metastases, a common metastatic site of SCLC.  
Preliminary data from Phase 1 studies has demonstrated some efficacy of PARP inhibitors in 
SCLC patients. In a Phase 1 study, talazoparib was administered as a single agent in patients 
with previously treated advanced SCLC. [53] In this study, 10% of patients treated with 
talazoparib had a partial response and 25% had a clinical benefit (complete response, partial 
response and stable disease ≥ 16 weeks) with a median duration or response of 13.7 weeks 
(95% CI; 12.0, 15.3 weeks). The most common adverse events in this study were 
myelo-suppression, fatigue, nausea, and alopecia. 
A Phase 1 study of velaparib administered in combination with standard doses of cisplatin and 
etiposide was conducted in treatment-naïve patients with extensive stage SCLC (n = 9). [54] 
The recommended phase 2 dose of velaparib was 100 mg. The preliminary efficacy in 
7 evaluable patients were: 1 complete response (14.3%), 4 partial response (57.1%), and 2 had 
stable disease (28.6%). Grade 3-5 hematologic adverse events included neutropenia, 
leukopenia, lymphopenia, and thrombocytopenia. 
The correlation of anti-tumor activity of immune checkpoint inhibitors with high mutational 
burden in solid tumors provides a rationale for investigating tislelizumab in extensive stage 
SCLC. The reported rates of PD-L1 expression on SCLC range between 27% to 72%. [55, 56] 
Early phase clinical trials with pembrolizumab and nivolumab have demonstrated anti-tumor 
activity with overall response rates ranging between 13% with nivolumab and 35% with 
pembrolizumab; 
confirmatory 
trials 
are 
ongoing 
(ClinicalTrials.gov 
Identifiers: 
NCT02359019, NCT02481830). 
2.5.2.5 Gastric Cancer (existing cohort) 
Genetic abnormalities in gastric cancer include alterations in the DNA damage response gene 
ATM. The loss of ATM has been demonstrated to be synthetically lethal with inhibition of 
PARP, supporting the use of platinum-based treatment as well as PARP inhibitors.  
Studies showed that gastric cancer cell lines, particularly those with a low expression level of 
ATM protein, are sensitive to olaparib. [57, 58] A randomized double-blind placebo-controlled 
Phase 2 study was conducted in 124 patients with recurrent or metastatic gastric cancer treated 
with olaparib (100 mg twice daily) in combination with paclitaxel (80 mg/m2 on days 1, 8, and 
15 of every 28-day cycle) or placebo. [59] Results from this study showed the combination 
therapy significantly improved overall survival (OS) in both the overall population (median 
13.1 vs 8.3 months) and in those whose tumors contained low levels of ATM protein. However, 
there was no difference in progression-free survival (PFS) in either the overall population or 
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A Phase 3 clinical study with paclitaxel with or without olaparib as a second line treatment 
recently reported results. [60] In this study, Asian patients with advanced, previously treated 
gastric cancer were treated with either paclitaxel or paclitaxel in combination with the PARP 
inhibitor olaparib. Eighteen percent of 535 patients randomized were ATM-deficient. Results 
of the study in the overall population demonstrated numerically higher overall survival for 
patients treated with olaparib plus paclitaxel (6.9 vs 8.8 months, HR 0.79, p = 0.0262). 
However due to a statistical correction made due to inclusion of a co-primary endpoint of the 
ATM deficient subgroup, this did not reach statistical significance (which would have required 
a p-value of < 0.025). In the ATM deficient subgroup, radiological response rates were 
significantly higher for patients treated with olaparib (37% vs 16%, p = 0.03), and a non-
statistically significant trend towards improvement in overall survival was also noted (10 vs 
12 months, HR 0.73, p = 0.2458). Combination therapy was well-tolerated, with no new safety 
signals demonstrated. A Phase 1 clinical study with veliparib is currently ongoing. [61] 
Several preclinical and clinical studies support targeting the PD-1 pathway in gastric cancer. 
A comprehensive genomic characterization of gastric carcinoma identified a subset of gastric 
cancers that may have elevated PD-1/PD-L1 expression, which provides the rationale for 
treating patients with gastric cancer with immune checkpoint inhibitors. [62] The incidence of 
PD-L1 expression in gastric cancer samples is approximately 40%, but the clinical relevance 
of this finding is inconsistently reported. [63, 64] The rationale to evaluate immune checkpoint 
inhibitors in gastric cancer is, therefore, based on the recognized immune-modulatory 
mechanisms of action of these molecules. As such, multiple agents targeting the PD-1/L-1 
system are currently in development for patients with gastro-esophageal cancer. Preliminary 
results of these trials support anti-tumor activity of these agents when given as monotherapy. 
[63, 65]  
To date, the preliminary data combining pamiparib with tislelizumab supports the safety of the 
combination when given to patients with advanced solid tumors. Given the unmet medical 
need in advanced gastric cancer, exploring the efficacy of this combination has merit. 
2.5.2.6 Urothelial (muscle-invasive bladder, ureter, urethra, renal pelvis) Cancer  
The standard of care for patients who have muscle-invasive bladder cancer is platinum-based 
chemotherapy. [66] The median overall survival in patients with metastatic disease is 
approximately 9-15 months, an indication that more effective treatment is needed for this 
patient population.   
Whole genome sequencing on bladder cell lines was performed as part of a TCGA 
collaboration to identify biologic and genomic profiles that may be predictive of platinum 
response in patients with bladder cancer. [67] In this experiment, alterations in the BRCA DNA 
repair pathway were identified in 44% of the cell lines tested, and in 32% of the tumors from 

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patients in the TCGA database. Another collaboration found a significant association between 
somatic mutations in DNA repair genes and improved clinical outcomes. [68] To date, there 
are no clinical trials of PARP inhibition in the bladder cancer population. 
The recent data from the KEYNOTE-045 study (ClinicalTrials.gov Identifier: NCT02256436) 
demonstrates an improved survival in patients with metastatic urothelial cancer with 
pembrolizumab treatment. Other checkpoint inhibitors, atezolizumab and nivolumab, have 
demonstrated efficacy in advanced urothelial cancer and are FDA-approved for this indication. 
[69, 70] Administering pamiparib prior to tislelizumab in advanced urothelial cancer will 
evaluate if upregulating neoantigens with pamiparib will influence the response to checkpoint 
inhibition with tislelizumab. Eligible patients will be required to have disease considered to be 
responsive to platinum-based chemotherapy to increase the chance of responding to PARP 
inhibition. 
2.5.2.7 Pancreatic Cancer  
Whole genome analysis of pancreatic tumors estimate 10% to 12% of patients with pancreatic 
cancers have either germ-line or somatic mutations of BRCA2-, BRCA1- or PALB2. [71] There 
are an additional 12% to 13% of patients who are characterized with ‘BRCAness’ and who 
might be sensitive to PARP inhibition. Platinum-containing regimens or PARP inhibitors have 
been used in patients with pancreatic cancer with known BRCA mutations. [72, 73] Data from 
an open-label Phase 2 study of rucaparib supports the use of PARP inhibitors in patients with 
advanced BRCA1/2 mutated pancreatic cancer. One complete and 2 partial responses were 
observed in the 19 patients enrolled. All responses were observed in patients who had received 
only one prior treatment for advanced pancreatic cancer. One retrospective report evaluating 
the clinical significance of BRCA1/2 mutations in pancreatic cancer reported an improvement 
in overall survival in patients with Stage 3 or 4 pancreatic adenocarcinoma who received 
platinum–based treatment relative to historic reports. [74] This data supports the use of PARP 
inhibitors in patients with pancreatic cancer. Multiple trials with PARP inhibitors are ongoing 
with veliparib, talazoparib, neraparib, and olaparib. 
Immune checkpoint inhibitors are currently being evaluated in early phase clinical trials in 
patients with pancreatic cancer in both the neo-adjuvant and palliative care settings.  
Historically, pancreatic cancer was considered a “non-immunogenic” tumor, with low 
PD-L1/PD-1 expression, low amounts of CD8+ T-cell infiltration and a low tumor mutation 
burden. These characteristics were thought to be indicators of a relative unresponsiveness to 
immune checkpoint inhibitors as well as the poor prognosis associated with this disease. 
Recently, an investigation using murine models and human tissue specimens detailed a 
mechanism to up-regulate PD-L1 in pancreatic cancer. MLL1, a human mixed lineage 
leukemia protein-1, was expressed in the majority (11 of 13) of the pancreatic tumor cell lines 
evaluated, and after binding to a promotor of the CD274 gene, PD-L1 expression increased, as 
did the efficacy of anti-PD-1 monoclonal antibodies.  

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In summary, there is a scientific rationale to administer PARP inhibitors and immune 
checkpoint inhibitors in combination to patients with advanced pancreatic cancer. 
 

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3.0 STUDY OBJECTIVES 
3.1 
Part A (Dose Escalation) 
3.1.1 Primary Objectives 
 
To assess the safety and tolerability of tislelizumab in combination with pamiparib 
 
To determine the MTD and RP2D for the combination 
3.1.2 Secondary Objectives 
 
To characterize the PK of pamiparib and tislelizumab in combination  
 
To assess the preliminary anti-tumor activity of tislelizumab in combination with 
pamiparib 
 
To assess host immunogenicity to tislelizumab 
3.1.3 Exploratory Objectives 
 
 
3.2 Part B (Expansion Cohorts) 
3.2.1 Primary Objectives 
 
To assess the preliminary anti-tumor activity of the combination of tislelizumab and 
pamiparib in patients with specific tumor types 
3.2.2 Secondary Objectives 
 
To further assess the safety and tolerability of the combination 
 
To further characterize the PK of tislelizumab and pamiparib in combination 
 
To further assess host immunogenicity to tislelizumab 
3.2.3 Exploratory Objectives 
 
 

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4.0 STUDY ENDPOINTS 
4.1 
Part A (Dose Escalation) 
4.1.1 Primary Endpoints 
 Safety and tolerability as assessed by the incidence and nature of AEs 
 Incidence and nature of DLTs  
 Determination of MTD of the combination of tislelizumab and pamiparib 
4.1.2 Secondary Endpoints 
 Pharmacokinetic parameters, including but not limited to Ctrough of tislelizumab and Cmax, 
Tmax and Ctrough of pamiparib  
 Efficacy parameters including: 
o Objective response rate (ORR) is defined as a best overall response of complete 
response (CR) and partial response (PR) 
o Disease control rate (DCR) is defined as a best overall response of CR, PR and 
stable disease (SD) 
o Clinical benefit rate (CBR) is defined as a best overall response of CR, PR and SD 
lasting ≥ 24 weeks 
o Progression-free survival (PFS) is defined as the time from first dose of study 
medication to the first documented objective disease progression or death due to 
any cause, whichever occurs first 
o Overall survival (OS) is defined as the time from the date of first dose of study drug 
to death due to any cause 
 Immunogenicity of tislelizumab 
4.1.3 Exploratory Endpoints 
 

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4.2 
Part B (Expansion Cohorts) 
4.2.1 Primary Endpoints 
 Anti-tumor activity as determined by ORR, PFS, duration of response (DOR), DCR, CBR, 
and OS 
4.2.2 Secondary Endpoints 
 Safety and tolerability as assessed by the incidence and nature of AEs 
 Pharmacokinetic parameters, including but not limited to Ctrough of tislelizumab and 
pamiparib 
 Immunogenicity of tislelizumab 
4.2.3 Exploratory Endpoints 
 
 

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5.0 INVESTIGATIONAL PLAN 
5.1 
Summary of Study Design 
This is a 2-part Phase 1, open label, multiple dose, dose-escalation and expansion study to 
investigate the safety, pharmacokinetics and antitumor activity of the anti-PD-1 monoclonal 
antibody tislelizumab in combination with the PARP inhibitor pamiparib in patients with 
advanced solid tumors. 
Part A consists of a dose-escalation and dose-finding component to establish the MTD and/or 
RP2D to evaluate the safety, PK, preliminary anti-tumor activity of tislelizumab and pamiparib 
combination and immunogenicity of tislelizumab. Part B will evaluate the safety and 
tolerability, PK and preliminary anti-tumor activity of tislelizumab 200 mg IV Q3W combined 
with pamiparib 40 mg orally twice daily (see Section 6.2 for instructions). 
In Part A of the study in all DLs, tislelizumab will be given intravenously (IV) on Day 1 of 
each 21-day cycle, and pamiparib will be taken orally twice daily starting from Day 1.  
Part A of the study will follow a 3+3 dose-escalation scheme at pre-defined DLs until MTD 
and/or RP2D is determined for the combination. Dose escalation continues until 2 patients 
experience DLT at a DL, ie, 2 in 3 to 6 treated patients. The DLT assessments will be evaluated 
during the first cycle consisting of the first 21 days of treatment. However, if during dose-
escalation, a MTD cannot be established after the evaluation of all planned doses, eg, because 
further increase in dose does not result in significant increases in exposure, then a RP2D will 
be determined after the evaluation of available data on safety, PK, and efficacy data. The 
selection of the RP2D will be based on the safety and preliminary anti-tumor activity observed 
in Part A, and other complementary data and made at the SMC meeting at the time that the 
dose for Part B is decided. 
After the first patient in the first DL receives Day 1 dose of the Cycle 1, subsequent patients 
will not be dosed until the first patient has been observed for at least 24 hours to exclude 
unexpected acute toxicity. 
An SMC (see Section 8.4.1 for committee composition) will determine the DLs to be 
administered and dose regimen during dose escalation and at the SMC meetings. The decision 
will depend on the available data on safety, PK and preliminary anti-tumor activity. The SMC 
will also decide and select the RP2D. 
Part B will be to further evaluate the PK, safety, and tolerability of the combination of 
tislelizumab and pamiparib and to assess the preliminary anti-tumor activity of the combination 
in patients in the arms of specific tumor types defined in Section 5.1.2.  The number of patients 
planned in each arm is listed in Section 5.1.2.  

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Baseline tumor tissue is mandatory for biomarker analysis, either from archived tumor tissue 
or fresh tumor biopsies unless it has been previously discussed with the sponsor’s medical 
monitor or its designee. Fresh blood samples at baseline for all patients with ovarian, fallopian 
tube, primary peritoneal, or breast cancer in Part A and all patients enrolled in Part B must be 
collected for evaluation of germline BRCA mutations and/or confirmation of prior BRCA 
results.  
Patients will be monitored for safety, tolerability, anti-tislelizumab antibodies, and anti-tumor 
activity throughout the study from the day of first administration of study drugs up to 30 days 
after the last dose of pamiparib and 90 days following last dose of tislelizumab or initiation of 
new anticancer therapy, whichever occurs first. The exception are irAEs, which will be 
recorded up to 90 days after the last dose of tislelizumab, regardless of initiation of subsequent 
anticancer therapy. 
Radiological assessment of tumor response should be performed approximately every 
9 ± 1 weeks in the first year and approximately every 12 ± 1 weeks thereafter. 
If any subject has a confirmed CR, PR, or SD after 2 years of study treatment, either 
tislelizumab or pamiparib or both agents can be stopped provided the study assessments and 
procedures are performed every 12 weeks with every radiographic tumor assessment. If a 
subject has evidence of PD within 1 year of treatment interruption, the Investigator can 
consider restarting the combined study treatment after discussion with the Sponsor, contingent 
on the continued availability of study medications. 
The rationale for this change: a treatment hiatus for patients who have durable responses is 
allowed at the discretion of the treating investigator in consultation with the Sponsor.  The 
optimal duration of combined study treatment is not known, and a treatment hiatus may reduce 
patient burden. During the treatment hiatus, patients will be monitored with routine 
radiographic tumor assessments according to the protocol schedule and If there are indications 
of tumor progression, study treatment can be resumed. 
This study will be considered complete once all patients have manifested disease progression, 
ceased study treatment due to death, exhibited intolerance, withdrawn consent from the study, 
or completed a total of 2 years of treatment. Any patient in this study who continues to 
demonstrate objective clinical benefit at the end of a 2-year treatment duration may continue 
in the study or on treatment. 
A flow chart of the study design is presented in Figure 1 and Figure 2 below. 
 

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Figure 1: Overall Study Design (Part A; All Dose Levels) 
 
Screening 
Day -28 to Day -11 
 
Cycle 1 
Day 1 
 
tislelizumab + 
pamiparib 
 
Cycle 1 
Day 2 to Day 21 
 
pamiparib 
 
Subsequent cycles 
 
Day 1 
 
tislelizumab + 
pamiparib 
 
 
Safety Follow-up 
30 days  
(± 7 days) after the 
last pamiparib dose 
and 90 days (± 14 
days) after the last 
tislelizumab dose 
 
 
 
 
 
Day 2 to Day 21 
 
pamiparib 
 
1. 
Screening assessments will be completed within 28 days prior to the first dose of the study drug. 
Note: tislelizumab 200 mg will be administered as an IV infusion on Day 1 of a 21-day cycle, and pamiparib 40 mg will be taken orally twice daily starting from Day 1. 
 
 

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Figure 2: Overall Study Design (Part B1) 
 
Pre-screening 
Day -84 to 
Screening2 
 
Screening 
Day -28 to 
Day -13 
 
Cycle 1 
Day 1 
 
tislelizumab 
+ pamiparib 
 
Cycle 1 
Day 2 to 
Day 21 
 
pamiparib 
 
Subsequent cycles 
 
Day 1 
 
tislelizumab + 
pamiparib 
 
 
Safety Follow-up 
30 days  
(± 7 days) after the 
last pamiparib 
dose; 90 days (±14 
days) after the last 
dose of 
tislelizumab 
 
 
 
 
 
 
 
 
 
 
Day 2 to Day 21 
 
pamiparib 
 
1. 
The decision to implement this schedule in Part B will be made after all the data from Part A is reviewed. 
2. 
Patients who do not have known germline or somatic BRCA mutation or known HRD for Arm 1 (ovarian cancer), Arm 2 (TNBC), and Arm 3 (mCRPC) will have a HRD 
pre-screening period of up to 12 weeks prior to eligibility screening (see Section 8.1 for details). A separate pre-screening informed consent must be obtained. Any tissue 
taken during pre-screening period will not be re-collected during screening stage. 
3. 
Screening assessments will be completed within 28 days prior to the first dose of the study drug. 
Note: Tislelizumab 200 mg will be administered as an IV infusion on Day 1 of a 21-day cycle, and pamiparib 40 mg will be taken orally twice daily starting from Day 1. 
 
 

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5.1.1 Part A: Dose Escalation and Dose Finding 
Five DLs are planned, as shown in Table 1. The starting dose for pamiparib and tislelizumab 
was based on the doses evaluated in the on-going monotherapy Phase 1 study of pamiparib and 
tislelizumab and is significantly lower than the highest safe dose that has been identified to 
date. 
The suggested dose-escalation scheme is presented in Table 1 below. The proposed DLs may 
be further modified and additional doses may be considered based on the safety, tolerability, 
and efficacy observed during dose escalation, ie, flat dose of tislelizumab at 200 mg IV Q3W, 
an intermediate, not pre-defined or not previously evaluated dose or a less frequent dosing 
schedule that will not exceed the MTD level, if evaluation of toxicity at such a dose or schedule 
is desired. 
Table 1: Suggested Dose-Escalation Scheme 
Proposed Dose 
Level 
Total daily dose1 
Tislelizumab 
Pamiparib 
1 
2 mg/kg IV Q3W 
20 mg orally twice daily 
2 
2 mg/kg IV Q3W 
40 mg orally twice daily 
3 
2 mg/kg IV Q3W 
60 mg orally twice daily 
4  
200 mg IV Q3W 
40 mg orally twice daily 
5 
200 mg IV Q3W 
60 mg orally twice daily 
Abbreviations: IV: intravenous; Q3W: every 3 weeks 
1 The actual dose levels and dose regimens administered in each step will depend on the data available from the 
previous step, as determined by the Safety Monitoring Committee. 
The evaluable patients are those who have met the minimum treatment and safety evaluation 
requirements of the study and/or who experience a DLT during the first cycle (21 days). The 
minimum treatment and safety evaluation requirements include 1) treatment of > 90% of 
tislelizumab infusion on Cycle 1 Day 1 (C1D1); 2) a minimum of total 16 days of pamiparib 
treatment (> 75% of the expected dose) during Cycle 1; and 3) observation of ≥ 21 days 
following C1D1 treatment and completion of the scheduled safety assessments. If patients do 
not meet these minimum treatment and safety evaluation requirements, they will be regarded 
as ineligible for inclusion for MTD evaluation and may be replaced, if needed, based on 3+3 
escalation scheme.  
5.1.1.1 Dose-Limiting Toxicity 
A DLT (Table 2) is defined as an adverse event or abnormal laboratory value assessed as 
unrelated to disease progression, intercurrent illness, or concomitant medications, and occurs 

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during the first 21 days following the first dose of tislelizumab and pamiparib in Cycle 1 and 
meets any of the following criteria: 
Table 2: Dose-limiting Toxicity Assessment Criteria 
Toxicity 
Any of the following criteria: 
Hematologic 
1. Grade 4 neutropenia lasting > 7 days 
2. Febrile neutropenia (defined as absolute neutrophil count [ANC] 
< 1000/mm3 with a single temperature of 38.3ºC or a sustained 
temperature of 38ºC for > 1 hour) 
3. Grade 3 thrombocytopenia with bleeding 
4. Grade 4 thrombocytopenia 
5. Grade 4 (life threatening) anemia 
Non-hematologic 
1. Grade 5 adverse events 
2. Grade 4 toxicity  
3. Grade 3 toxicities irrespective of duration, with the exception of 
laboratory abnormalities, diarrhea, nausea and vomiting, and 
asymptomatic biochemical abnormalities that improve to Grade 
2 or lesser severity within 3 days of institution of supportive care 
4. Grade 3 tumor flare (defined as local pain, irritation, or rash 
localized at sites of known or suspected tumor) of > 7-day 
duration 
5. Immune-related adverse events (irAE) of Grade 3 or greater 
severity 
6. Grade 4 laboratory abnormalities irrespective of duration 
7. Grade 2 ophthalmologic toxicities 
8. Persistent Grade 2 toxicity such as nausea, vomiting, fatigue 
despite optimal standard medical therapy that in the opinion of 
the investigator prevents continuous dosing. 
CTCAE version 4.03 will be used for all grading. 
Optimal therapy for vomiting or diarrhea will be based in institutional guidelines, with 
consideration of the prohibited medications listed in this protocol. 
The investigator must notify the sponsor or its designee as soon as possible of any unexpected 
CTCAE Grade ≥ 3 adverse events or laboratory abnormalities.  
5.1.2 Part B: Expansion 
Part B is a multicenter, open-label, multiple-arm, expansion study that will evaluate the safety 
and tolerability and anti-tumor activity of tislelizumab + pamiparib treatment. Up to 40 

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enrolled patients/cohort are planned to be included for expansion in Part B of the study in the 
arms of specific tumor types defined below.  Each Arm will be evaluated independently for 
study endpoints. The purpose of these expansion arms is to explore signals of clinical efficacy 
as well as to confirm the safety and tolerability of the combination in each selected tumor type. 
Anti-tumor activity will be evaluated in Part B. Initially, 20 patients per cohort will be enrolled 
and evaluated for anti-tumor activity. A decision can be made to stop an arm early due to 
suboptimal clinical anti-tumor activity or to enroll an additional 20 patients to evaluate further 
the anti-tumor activity. Statistical justification of such sample size expansion will be included 
in the final statistical analysis plan as applicable. 
The RP2D is tislelizumab 200 mg IV Q3W + pamiparib 40 mg orally twice daily. This 
combination will be given until disease progression or other discontinuation criteria are met. 
All patients must have received standard of care in the primary treatment of their disease. 
Patients with platinum-refractory disease are excluded.  Platinum-refractory disease is 
defined as progressive disease at the time of the first tumor assessment while receiving a 
platinum-containing therapy. Enrollment into these disease-specific cohorts will occur 
simultaneously and independent of each other.  For all disease-specific cohorts, a line of 
treatment begins with the administration of the first agent in a regimen and ends at the time 
of disease progression.  Except as noted, at least 1 prior line of treatment should have 
contained a platinum compound. 
Arm 1a: Patients with relapsed, platinum-sensitive high grade epithelial, non-mucinous, 
ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) with either known 
germline or somatic BRCA1/2 mutations or with homologous recombination 
deficiency (HRD). Patients must have received at least 2 prior lines of 
platinum-containing chemotherapy 
Arm 1b: Patients with relapsed, platinum-sensitive high grade EOC without either known 
germline or somatic BRCA1/2 mutations and without known HRD. Patients must 
have received at least 2 prior lines of platinum-containing chemotherapy. 
Arm 2: Patients with triple negative breast cancer (TNBC) with either known germline or 
somatic BRCA1/2 mutations or with documented HRD.  Patients can have been 
treated with at least 1 but no more than 3 prior lines of treatment.   

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Arm 3: Patients with metastatic castration-resistant prostate cancer (mCRPC) with either 
known germline or somatic BRCA1/2 mutations or with documented HRD. 
Chemotherapy-naïve patients must have received prior abiraterone acetate or 
enzalutamide treatment 
Arm 4: Patients with extensive-stage disease small cell lung cancer (SCLC) treated with at 
least 1 but no more than 2 prior lines of treatment, at least 1 must include a platinum 
agent 
Arm 5: Patients with HER2-negative gastric or gastroesophageal junction cancer.  Patients 
with HER2-negative disease may be treated with at least 1 but no more than 2 prior 
lines of treatment  
Arm 6: Patients with locally advanced or metastatic urothelial (muscle invasive bladder, 
ureter, urethra or renal pelvis) cancer treated with at least 1 but no more than 2 prior 
lines of treatment, including a prior platinum-containing chemotherapy  
Arm 7: Patients with advanced or metastatic pancreatic adenocarcinoma treated with at least 
one but no more than 2 prior lines of therapy. At least 1 prior treatment for advanced 
or metastatic disease must have contained a platinum agent. Any potential patient with 
a known deleterious germline or somatic BRCA is eligible even if platinum-naïve 
Arm 8: (NOTE: CLOSED TO ENROLLMENT) Patients who may be expected to benefit 
from the combination of a PARP inhibitor and a PD-1 inhibitor. This arm will include 
patients with recurrent non-ovarian gynecological cancers (endometrial cancer, cancer 
of the cervix and patients with tumors known to be mismatch repair deficient [MMR] 
or HRD positive) that are not eligible for inclusion in any other arms of the trial. This 
is an exploratory signal seeking arm  
For Arm 1 (ovarian cancer), Arm 2 (TNBC), and Arm 3 (mCRPC), patients with known 
eligible mutation status can be enrolled into the study if otherwise eligible. Tissue/blood 
specimens will be collected for a confirmatory test. Patients who do not have known germline 
or somatic BRCA mutation, or known HRD status must sign a separate pre-screening informed 
consent to evaluate HRD status prior to enrollment. Please see Section 8.1 for details. 
For Arm 1 (EOC), Arm 1a will be analyzed independently of Arm 1b. All Arms may enroll up 
to 40 patients. 
The Sponsor’s medical monitor will approve tumor types for Arm 8 prior to screening. 
The cycle length for tislelizumab and pamiparib combination treatment is 21 days.  
5.1.3 Schedule of Assessments 
The schedule of assessments for Part A; all Dose Levels and Part B of the study are presented 
in Table 3, Table 4, Table 5, and Table 6. 

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Table 3: Part A; All Dose Levels: Study Assessments and Procedures Schedule 
Procedure 
Screening1 
Treatment Period 
Safety Follow-up2 
Survival Follow-up3 
Cycle 1 (21 Days) 
Cycles ≥ 2 
Day 
-28 to -1 
1 
8  
± 1 
15  
± 1 
1  
± 2 
Day 30  
± 7 Days after the 
last pamiparib 
dose and 90 days 
(± 14 days after 
last tislelizumab 
dose 
Approximately 
Every 3 months 
Informed consent4 
X 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
Demographic/Medical 
History/ Prior 
Medications5 
X 
 
 
 
 
 
 
Vital signs/Weight6 
X 
X 
X 
X 
X 
X 
 
Physical examination7 
X 
X 
 
X 
X 
X 
 
Ophthalmologic 
examination8 
X 
As clinically indicated 
X 
 
ECOG performance 
status 
X 
X 
 
 
X 
X 
 
12-lead ECG9 
X9 
X 
 
 
X9 
X 
 
Adverse Events 
Assessment10 
X 
X 
X 
X 
X 
X 
 
Review Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
 
CBC with 
Differential11 
X 
X 
 
X 
X 
X 
 

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Table 3: Part A; All Dose Levels: Study Assessments and Procedures Schedule 
Procedure 
Screening1 
Treatment Period 
Safety Follow-up2 
Survival Follow-up3 
Cycle 1 (21 Days) 
Cycles ≥ 2 
Day 
-28 to -1 
1 
8  
± 1 
15  
± 1 
1  
± 2 
Day 30  
± 7 Days after the 
last pamiparib 
dose and 90 days 
(± 14 days after 
last tislelizumab 
dose 
Approximately 
Every 3 months 
Comprehensive Serum 
Chemistry Panel11 
X 
X 
X 
X 
X 
X 
 
CK, CK-MB11 
X 
X 
 
 
X 
X 
 
Coagulation 
Parameters12 
X 
 
 
 
 
X 
 
Urinalysis11 
X 
 
 
 
 
X 
 
Pregnancy Test13 
X 
 
 
 
X 
 
 
Thyroid Function14 
 
X 
 
 
X14 
X 
 
Immunoglobulins15 
 
X 
 
 
X15 
X 
 
Anti-tislelizumab 
Antibodies16 
 
X 
X16 
 
X16 
 
 
Pharmacokinetics blood 
sampling17 
 
X 
X17 
 
X17 
 
 
HIV, hepatitis B and 
C18 
X 
 
 
 
 
 
 
 
   
 
 
 
 
Tumor Imaging20 
X 
 
 
 
X 
X 
 

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Table 3: Part A; All Dose Levels: Study Assessments and Procedures Schedule 
Procedure 
Screening1 
Treatment Period 
Safety Follow-up2 
Survival Follow-up3 
Cycle 1 (21 Days) 
Cycles ≥ 2 
Day 
-28 to -1 
1 
8  
± 1 
15  
± 1 
1  
± 2 
Day 30  
± 7 Days after the 
last pamiparib 
dose and 90 days 
(± 14 days after 
last tislelizumab 
dose 
Approximately 
Every 3 months 
Tislelizumab 
administration  
(30-60 minutes infusion 
every 21 days) 21  
 
X 
 
 
X 
 
 
Pamiparib 
administration (twice 
daily) 21 
 
Continuous 
 
 
Archival Tumor 
Tissue22 
X 
 
 
 
 
 
 
Fresh Tumor Tissue23  
X 
 
 
X 
 
X 
 
BRCA test of Blood 
sample collection24 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X25 
X 
 
Survival Status 
 
 
 
 
 
 
X 
Abbreviations: ECOG: Eastern Cooperative Oncology Group; X: to be performed; DLT: dose-limiting toxicity; ECG: electrocardiogram; CBC: complete blood 
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1  
If screening laboratory tests are completed within 14 days prior to first dose, pre-dose samples on Day 1 of Cycle 1 will not be repeated. 
2  
The mandatory Safety Follow-up Visits should be conducted 30 days (± 7 days) after the last dose of study therapy, or before initiation of a new anticancer 
treatment. Patients who are discontinued from the study due to an unacceptable drug-related adverse event will be followed until the resolution of the AE to 
Grade 0-1, baseline or stabilization or until beginning of a new therapy for their cancer, whichever occurs first. 
3  
Following completion or discontinuation of the treatment and/or Safety Follow-up phases of the study, every effort should be made to follow up all patients 
for their survival status until patient death. 
4  
Written consent must be obtained prior to performing any protocol-specific procedure. Results of a test performed as part of routine clinical management are 
acceptable in lieu of a screening test if performed within the specified time frame (eg, within 28 days prior to Cycle 1, Day 1). A patient-specific patient 
number will be assigned when the study informed consent is signed. 
5  
Includes history of all prior systemic, radiation, and surgical treatment for the primary cancer diagnosis. Radiographic studies performed prior to study entry 
may be collected for review by the investigator. Report non-cancer treatment medication up to 30 days prior to the Screening visit. Date and response to last 
platinum-containing chemotherapy treatment and date of the progression must be documented unless no platinum-containing treatment has been received 
before. 
6  
Vital signs to include temperature, heart rate, respiratory rate and blood pressure. 
7  
Full physical examination includes the following items: 1. general appearance; 2. head, eyes, ears, nose and throat; 3. neck; 4. heart; 5. chest (including lungs); 
6. abdomen; 7. extremities; 8. skin; 9. lymph nodes; 10. cardio-vascular; 11. neurological status. 
8  
Ophthalmologic examination includes visual acuity, funduscopic, and slit lamp microscopy. The exam will be performed during the screening period, on 
Cycle 2 Day 1 ± 2 days, Cycle 4 Day 1 ± 2 days, Safety Follow-up, and whenever clinically indicated. 
9  
Electrocardiogram assessments are to be performed with the patient in semi-recumbent supine position and rested for 5 minutes. Electrocardiogram (12-lead 
ECG) should be performed at Screening within 14 days of Cycle 1 Day 1 as baseline, and at the mandatory Safety Follow-up Visits. Triplicate ECG recordings 
(3 readings in rapid succession and not more than 2 minutes apart) will be obtained locally at the site in conjunction with blood sampling for pharmacokinetics 
as per Table 4. Additional ECGs may be obtained if clinically indicated (Section 8.3.4). 
10  
Adverse Events and laboratory safety measurements will be graded per NCI-CTCAE version 4.03. All adverse experiences, whether gradable by CTCAE or 
not, will also be evaluated for seriousness and causality. 
11  
Routine laboratory tests (eg, CBC with differential; comprehensive serum chemistry panel; urinalysis) will be performed by the local study site laboratory or 
their contract laboratory. Serum chemistry and hematology will be performed at Screening, prior to the first dose of pamiparib if it was not done within 14 
days of Cycle 1 Day 1, Days 1 and 15 of Cycles 1 through 3, and Day 1 of subsequent cycles and more frequently as clinically indicated. CK and CK-MB 
will be performed at Screening, prior to the first dose on Day 1 of all treatment cycles, and Safety Follow-up Visit. If your laboratory does not perform CK-
MB testing, serum troponins (troponin I and/or T) measurements should be performed instead; if only either troponin is assessed per local standards the same 
should be evaluated throughout.  See Appendix 10 for management of immune-related adverse events corresponding to abnormalities based on laboratory 
testing. 
12  
PT/INR and activated partial thromboplastin time (aPTT) should be collected at Screening and at the mandatory Safety Follow-up Visits after discontinuation 
of study therapy. Coagulation parameters should be determined throughout the study when clinically indicated. PT/INR and aPTT will be analyzed by the 
local study site laboratory. 
13  
Women of childbearing potential must have a negative serum pregnancy test at Screening (within 7 days of the first investigational product administration). 
A urine or serum pregnancy test must be performed if any woman suspects that she has become pregnant during the study. For subsequent pregnancy testing, 

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urine pregnancy tests, performed at a central or local laboratory, are allowed. If a urine pregnancy test is positive, a confirmatory serum pregnancy test is 
required. 
14  
T3, T4, thyroid-stimulating hormone (TSH); will be collected at pre-dose of Day 1 of every cycle and at the mandatory Safety Follow-up Visits. Analysis of 
T3, T4 and TSH will be performed by the local study site laboratory. If feasible, early morning ACTH and cortisol will be obtained as part of the screening 
assessments and only repeated during the study if it is clinically indicated. 
15  
Analysis of IgG and IgM will be performed at pre-dose of Day 1 every cycle in first 12 months, approximately every 2 months thereafter, and at Safety 
Follow-up Visits. Analysis will be performed by the local study site laboratory. 
16  
Blood for anti-tislelizumab antibodies should be collected within 24 hours before the start of infusion on Day 1 of Cycle 1, on Day 8 of Cycle 1, and before 
the start of infusion on Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9 and approximately every 8 cycles thereafter (ie, Cycle 17, Cycle 25 and Cycle 
33).  In patients who discontinue study therapy before 6 months, every effort should be made to collect blood sample for analyzing anti-tislelizumab antibodies 
approximately 6 months after the first dose. Corresponding tislelizumab PK samples will be collected at the same time when the anti-drug antibody (ADA) 
samples are collected to assess the neutralizing capacity of ADA. Analysis will be performed by a central laboratory. 
17  
Cannulation for blood sampling for pharmacokinetics will be performed according to Table 4. In addition, corresponding tislelizumab PK samples will be 
collected at the same time when the ADA samples are collected to assess the neutralizing capacity of ADA.  
18  
Testing will be performed by the local laboratory at Screening. Include HCV antibody, HBsAg, HBcAb and HIV 1/2 antibodies, patients who are HBsAg 
and/or HBcAb positive or HCV antibody positive at Screening must not be enrolled until further definite testing with HBV DNA titers and HCV ribonucleic 
acid (RNA) tests can conclusively rule out presence of active infection requiring therapy with Hepatitis B and C respectively. 
19  
 
 
 
 
20  
Tumor imaging (either computed tomography [CT] or magnetic resonance imaging [MRI], with preference for CT) will be performed within 28 days prior to 
enrollment, and while on study approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks thereafter. The same imaging 
technique should be used in a patient throughout the study. After first documentation of response (CR or PR), imaging performed at the next regularly 
scheduled time point will be used for response confirmation. Progressive disease suspected as pseudo-progression needs to be confirmed in a subsequent 
imaging not less than 4 weeks later or at the next regularly scheduled time point but not more than 12 weeks, before discontinuation of study treatment. 
Patients who stop treatment prior to documentation of progressive disease will undergo repeated imaging for tumor response assessments as described in 
Section 5.2.5.1. In patients with prostate cancer, baseline bone scans will be performed during the Screening window, and repeat bone scans will be performed 
approximately every 9 ± 1 weeks for the first 12 months and approximately every 12 ± 1 weeks thereafter.  
21  
Both tislelizumab and pamiparib treatments start from Cycle 1 Day 1. On Day 1 of each cycle, tislelizumab will be given intravenously after the morning 
dosing of pamiparib. See Section 6.2 for additional information regarding the administration of study drugs. If any subject has a confirmed CR, PR, or SD 
after 2 years of study treatment, either tislelizumab or pamiparib or both agents can be stopped provided the study assessments and procedures are performed 
every 12 weeks with every radiographic tumor assessment. If a subject has evidence of PD within 1 year of treatment interruption, the Investigator can 
consider restarting the combined study treatment after discussion with the Sponsor, contingent on the continued availability of study medications.  The 
rationale for this change: a treatment hiatus for patients who have durable responses is allowed at the discretion of the treating investigator in consultation 
with the Sponsor.  The optimal duration of combined study treatment is not known, and a treatment hiatus may reduce patient burden. During the treatment 

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hiatus, patients will be monitored with routine radiographic tumor assessments according to the protocol schedule and If there are indications of tumor 
progression, study treatment can be resumed. 
22  
Collection of archival tumor tissue for purpose of biomarker analysis. This is a mandatory requirement for patient enrollment and should be specified in the 
consent form. Specific instructions for tissue collection and shipment are provided in the Laboratory Manual. 
23  
Archival tumor tissue will be collected for evaluation of potential biomarkers, although a fresh baseline tumor biopsy (within 12 weeks of starting treatment) 
is recommended. In the absence of archival tumor tissue, a fresh baseline biopsy of an accessible tumor lesion is mandatory, unless previously discussed with 
the sponsor’s medical monitor or its designee. For those patients who consent to fresh biopsy, an optional biopsy for biomarker analysis during the third week 
of the first cycle is recommended. For the patients who have confirmed disease progression, an optional biopsy may be taken at the Safety Follow-up visit.  
The purpose of this biopsy sample is to evaluate mechanisms of resistance to the study treatment(s). If feasible, any follow up biopsy should be ideally taken 
from the same anatomical location as the baseline biopsy. Additional written patient consent is required for optional fresh tumor biopsies. Fresh biopsies 
should be limited to readily accessible tumor lesions (eg, skin; peripheral lymph nodes; lung, liver or internal lymph node metastases which can be readily 
accessed using CT guidance). If performed, a tissue cylinder should be obtained that has proper size for histological examination and biomarker analysis. If 
any subject has a confirmed CR, PR, or SD after 2 years of study treatment, either tislelizumab or pamiparib or both agents can be stopped provided the study 
assessments and procedures are performed every 12 weeks with every radiographic tumor assessment. If a subject has evidence of PD within 1 year of 
treatment interruption, the Investigator can consider restarting the combined study treatment after discussion with the Sponsor, contingent on the continued 
availability of study medications.  The rationale for this change: a treatment hiatus for patients who have durable responses is allowed at the discretion of the 
treating investigator in consultation with the Sponsor.  The optimal duration of combined study treatment is not known, and a treatment hiatus may reduce 
patient burden. During the treatment hiatus, patients will be monitored with routine radiographic tumor assessments according to the protocol schedule and 
If there are indications of tumor progression, study treatment can be resumed. 
24  
A blood sample must be collected at screening stage for ovarian, fallopian tube, primary peritoneal, and breast cancer patients for germline BRCA and/or other 
mutations analysis. 
25  
 
 
 
 

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Sample collection must be from opposite arm to that used for study drug infusion. If drug was administered via a central venous catheter, sample collection for PK 
should be from a different site. 
1. 
In addition, corresponding tislelizumab PK samples will be collected at the same time points when the ADA samples are collected to assess the neutralizing 
capacity of ADA. General note: It is important that pharmacokinetic (PK) sampling occurs as close as possible to the scheduled time. In order to 
achieve this, some of the other assessments scheduled at the same time need to be initiated prior to or after the time point to allow for completion of 
these measurements in enough time for the PK sampling to be taken at the designated time point. Thus, the sequence at a particular time point is: 1) 
scheduled ECG; 2) PK blood samples 3) vital sign measurements; and 4) any other scheduled or unscheduled measurements at that time point. 
2  
Except for pre-dose PK, each PK/ADA sampling time point of tislelizumab and pamiparib will be in correspondence with the end of dosing of each agent, 
respectively.  
3  
The time points of performing ECG and vital signs will be associated with the time of pamiparib administration.  Triplicate ECG recordings (3 readings in rapid 
succession and not more than 2 minutes apart) will be obtained locally at the site.  
4  
Within 2 hours prior to dosing. 
5  
A window period of ± 5 minutes exists for all procedures occurring after the study drug is taken. 
6  
A window period of ± 10 minutes exists for all procedures occurring after the study drug is taken. 
7  
A window period of ± 30 minutes exists for all procedures occurring after the study drug is taken. 
8  
A window period of ± 1 hour exists for all procedures occurring after the study drug is taken. 

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Table 5: Part B: Study Assessments and Procedures Schedule 
 
Pre-
screening1 
Screening2 
Treatment Period (21 Day Cycles) 
Safety 
Follow-up3 
Follow-up4 
Cycles 1 to 3 
Cycle 4 through 6 
Cycle ≥ 7 
Day 
-84 to 
screening 
-28 to -1 
Day 1 
-1 
Day 8 
± 1 
Day 
15  
± 1 
Day 1  
± 2 
Day 15  
± 1 
Day 1  
± 2 
Day 30  
± 7 Days after 
the last 
pamiparib dose 
and 90 days 
(± 14 days after 
last 
tislelizumab 
dose 
Approximately 
Every 
3 months 
Pre-screening informed 
consent 
X 
 
 
 
 
 
 
 
 
 
Informed consent5 
 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
 
X 
 
 
 
 
 
 
 
 
Demographic/Medical 
History/ Prior 
Medications6 
 
X 
 
 
 
 
 
 
 
 
Vital signs/Weight7 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Physical examination8, 9 
 
X 
X 
 
 
X 
 
X 
X 
 
Optical Coherence 
Tomography (or 
equivalent diagnostic 
test), eye examination 
and visual acuity tests 10 
 
X 
Every 15 weeks (± 7 days) during treatment 
X11 
 
ECOG performance 
status 
 
X 
X 
 
 
X 
 
X 
X 
 
12-lead ECG12 
 
X 
 
 
 
 
 
 
X 
 

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Table 5: Part B: Study Assessments and Procedures Schedule 
 
Pre-
screening1 
Screening2 
Treatment Period (21 Day Cycles) 
Safety 
Follow-up3 
Follow-up4 
Cycles 1 to 3 
Cycle 4 through 6 
Cycle ≥ 7 
Day 
-84 to 
screening 
-28 to -1 
Day 1 
-1 
Day 8 
± 1 
Day 
15  
± 1 
Day 1  
± 2 
Day 15  
± 1 
Day 1  
± 2 
Day 30  
± 7 Days after 
the last 
pamiparib dose 
and 90 days 
(± 14 days after 
last 
tislelizumab 
dose 
Approximately 
Every 
3 months 
Review Adverse 
Events13 
X 
X 
X 
X 
X 
X 
 
X 
X 
X  AEs for 
tislelizumab 
only to 90 days 
Review alcohol 
consumption, 
concomitant 
Medications, herbals, 
mushroom containing 
products and 
supplements 
 
X 
X 
X 
X 
X 
 
X 
X 
 
CBC with Differential14 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Comprehensive Serum 
Chemistry Panel14 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
CK, CK-MB 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Coagulation 
Parameters15 
 
X 
Collect if Grade 2 or higher hepatic AE occurs at any time 
during the study and as clinically indicated 
X 
 
Urinalysis14 
 
X 
As clinically indicated 
X 
 
Pregnancy Test16 
 
X 
 
 
 
X 
 
X 
X 
 
Thyroid Function17 
 
X 
X 
 
 
X17 
 
X17 
X 
 

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Table 5: Part B: Study Assessments and Procedures Schedule 
 
Pre-
screening1 
Screening2 
Treatment Period (21 Day Cycles) 
Safety 
Follow-up3 
Follow-up4 
Cycles 1 to 3 
Cycle 4 through 6 
Cycle ≥ 7 
Day 
-84 to 
screening 
-28 to -1 
Day 1 
-1 
Day 8 
± 1 
Day 
15  
± 1 
Day 1  
± 2 
Day 15  
± 1 
Day 1  
± 2 
Day 30  
± 7 Days after 
the last 
pamiparib dose 
and 90 days 
(± 14 days after 
last 
tislelizumab 
dose 
Approximately 
Every 
3 months 
Anti-tislelizumab 
Antibodies18 
 
 
X 
X18 
 
X18 
 
X18 
 
 
Pharmacokinetics blood 
sampling19 
  
 
X 
X19 
 
X19 
 
X19 
 
 
HIV, hepatitis B, C and 
E20 
 
X 
Collect if Grade 2 or higher aminotransferase enzyme increases 
occur at any time during the study and as clinically indicated 
 
 
  
   
 
 
 
 
 
Tumor Imaging22 
 
X 
Every 9 weeks ± 1 week (calendar days)  
X 
 
Tislelizumab 
administration 
(30-60 minutes 
infusion) 23 
 
 
X 
 
 
X 
 
X 
 
 
Pamiparib 
administration (twice 
daily) 23 
 
 
Continuous 
 
 
Archival Tumor 
Tissue24 
X 
X 
 
 
 
 
 
 
 
 
Fresh Tumor Tissue25 
X 
X 
X 
 
 
 
X 
 

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Table 5: Part B: Study Assessments and Procedures Schedule 
 
Pre-
screening1 
Screening2 
Treatment Period (21 Day Cycles) 
Safety 
Follow-up3 
Follow-up4 
Cycles 1 to 3 
Cycle 4 through 6 
Cycle ≥ 7 
Day 
-84 to 
screening 
-28 to -1 
Day 1 
-1 
Day 8 
± 1 
Day 
15  
± 1 
Day 1  
± 2 
Day 15  
± 1 
Day 1  
± 2 
Day 30  
± 7 Days after 
the last 
pamiparib dose 
and 90 days 
(± 14 days after 
last 
tislelizumab 
dose 
Approximately 
Every 
3 months 
Blood sample collection 
for BRCA and/or other 
mutation test26 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
X27 
 
 
X 
 
Survival Status and 
subsequent anticancer 
therapy 
 
 
 
 
 
 
 
 
 
X 
Pulmonary function 
tests28 
 
X 
 
 
 
 
 
 
 
 
Abbreviations: AE: adverse event; ECOG: Eastern Cooperative Oncology Group; X: to be performed; DLT: dose-limiting toxicity; ECG: electrocardiogram; 
CBC: complete blood count 
1  
Patients who do not have known germline or somatic BRCA mutation or known HRD for Arm 1 (ovarian cancer), Arm 2 (TNBC), and Arm 3 (mCRPC) will 
have a HRD pre-screening period of up to 12 weeks prior to eligibility screening (see Section 8.1 for details). A separate pre-screening informed consent 
must be obtained. Any tissue taken during pre-screening period will not be re-collected during screening stage. 
2  
If screening laboratory tests, physical examination are completed within 14 days prior to first dose, pre-dose samples on Day 1 of Cycle 1 treatment will not 
be repeated. 
3  
The mandatory Safety Follow-up Visits should be conducted 30 days (± 7 days) after the last dose of pamiparib, 90 days (± 14 days) after the last dose of 
tislelizumab or before initiation of a new anticancer treatment. Patients who are discontinued from the study due to an unacceptable drug-related adverse 

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event will be followed until the resolution of the AE to Grade 0-1, baseline or stabilization or until beginning of a new therapy for their cancer, whichever 
occurs first. 
4  
Patients will be followed for survival, cause of death, and additional cancer treatment, if available, every 3 months, or when requested by the sponsor. 
5  
Written consent must be obtained prior to performing any protocol-specific procedure. Results of a test performed as part of routine clinical management are 
acceptable in lieu of a screening test if performed within the specified time frame (eg, within 28 days prior to Cycle 1, Day 1). Assign patient number when 
the study informed consent is signed. 
6  
Includes history of treatment for the primary cancer diagnosis, including prior systemic, radiation treatment and surgical treatment for the cancer. 
Radiographic studies performed prior to study entry may be collected for review by the investigator. Report non-cancer treatment medication up to 30 days 
prior to the Screening visit. Date and response to last platinum-containing chemotherapy treatment and date of the disease progression must be documented 
unless no platinum-containing treatment has been received before. 
7  
Vital signs to include temperature, heart rate, respiratory rate and blood pressure. 
8  
Full physical exam at the Screening and Safety Follow-up. At all other times, targeted or symptoms-directed physical examination, at the investigator’s 
discretion. 
9  
Investigators should evaluate patients for changes in vision, visual disturbance, or ocular inflammation at each scheduled study visit during tislelizumab 
treatment. For any change in vision, referral to an appropriate specialist will be made for further management guidance.  
10  Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test for retinal examination) captured as standard of care prior to 
obtaining written informed consent and within 28 days of randomization may be used rather than repeating tests. Eye exam, visual acuity test, and optical 
coherence tomography (or equivalent diagnostic test) will be assessed at the Screening Visit. Patients will undergo repeat assessments approximately every 
15 weeks (± 7 days) and at the safety follow up visit. Investigators should evaluate patients for changes in vision, visual disturbance, or ocular inflammation 
at each scheduled study visit during tislelizumab treatment. For any change in vision, referral to an appropriate specialist will be made for further 
management guidance. 
11  The ophthalmologic assessments including eye exam, visual acuity test, and OCT (or equivalent diagnostic test) should be performed during safety follow 
up, within 30 days of study treatment end.   
12  Electrocardiogram assessments are to be performed with the patient in semi-recumbent supine position and rested for 5 minutes. Electrocardiogram (12-lead 
ECG) should be performed at Screening within 14 days of Cycle 1 Day 1 as baseline, as clinically indicated during the treatment period at the investigator’s 
judgement, and at the mandatory Safety Follow-up Visits. Additionally, triplicate ECG recordings (3 readings in rapid succession and not more than 2 
minutes apart) will be obtained locally at the site in conjunction with blood sampling for pharmacokinetics as per Table 6.  
13  Adverse Events and laboratory safety measurements will be graded per NCI CTCAE version 4.03. All adverse experiences, whether gradable by CTCAE or 
not, will also be evaluated for seriousness criteria and causality. No adverse events will be reported during the pre-screening stage. Only serious adverse 
events will be reported during the pre-screening stage if the serious adverse event is related to the pre-screening procedure. All AEs and SAEs, regardless of 
the relationship to the investigational product, will be collected throughout the study until 30 days after the last study treatment or initiation of new 
anticancer therapy. The exception are irAEs, which will be recorded up to 90 days after the last dose of tislelizumab, regardless of initiation of subsequent 
anticancer therapy. 
14  Routine laboratory tests (eg, CBC with differential, comprehensive serum chemistry panel, and urinalysis) will be performed by the local study site 
laboratory or their contract laboratory. Serum chemistry and hematology will be performed at Screening, prior to the first dose of pamiparib if it was not 
done within 14 days of Cycle 1 Day 1, Days 1, 8, and 15 of Cycles 1 through 3, Days 1 and 15 of Cycles 4 through 6, and Day 1 of subsequent cycles and 
more frequently as clinically indicated, and at the mandatory Safety Follow-up Visits. CK and CK-MB will be performed at Screening, prior to the first dose 

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on Day 1, Day 8, and Day 15 of Cycles 1 through 3, prior to dosing on Day 1 for all remaining cycles, and Safety Follow-up Visit. If your laboratory does 
not perform CK-MB testing, serum troponins (troponin I and/or T) measurements should be performed instead; if only either troponin is assessed per local 
standards the same should be evaluated throughout. See Appendix 10 for management of immune-related adverse events corresponding to abnormalities 
based on laboratory testing. 
15  PT/INR and aPTT should be collected at Screening and at the mandatory Safety Follow-up Visits after discontinuation of study therapy. Coagulation 
parameters should be evaluated in the event of a Grade 2 or higher aminotransferase increases occur and as clinically necessary. Coagulation parameters will 
be analyzed by the local study site laboratory. 
16  Women of childbearing potential must have a negative serum pregnancy test at Screening (within 7 days of the first investigational product administration). 
A urine or serum pregnancy test must be performed on Day 1 of each cycle and at the Safety Follow-up and evaluated at the local site laboratory. 
17  T3, T4, thyroid-stimulating hormone (TSH); will be collected at Screening, every 2 cycles, or more frequently as clinically indicated during treatment, and at 
the mandatory Safety Follow-up Visits. Analysis of T3, T4 and TSH will be performed by the local study site laboratory. If feasible, early morning ACTH 
and cortisol will be obtained prior to the first dose of tislelizumab and only repeated during the study if it is clinically indicated. 
18  Blood for anti-tislelizumab antibodies should be collected within 24 hours before the start of infusion on Day 1 and one sample between Day 7 through 10 of 
Cycle 1, and before the start of infusion on Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9 and Cycle 17. Refer to Table 6 for details on timing of ADA 
sample collection. In patients who discontinue study therapy before 6 months, every effort should be made to collect blood samples to analyze anti-
tislelizumab antibodies approximately 6 months after the first dose. Corresponding tislelizumab PK samples will be collected at the same time when the 
ADA samples are collected to assess the neutralizing capacity of ADA. Analysis will be performed by a central laboratory. 
19  Blood for pharmacokinetics will be collected in Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9 and Cycle 17. Refer to Table 6 for details on timing of 
pharmacokinetics sample collection. In addition, corresponding tislelizumab PK samples will be collected at the same time when the ADA samples are 
collected to assess the neutralizing capacity of ADA. 
20  Testing will be performed by the local laboratory at Screening. Include HCV antibody, HBsAg, HBcAb and HIV 1/2 antibodies, patients who are HBsAg 
and HBcAb positive or HCV antibody positive at Screening must not be enrolled until further definite testing with HBV DNA titers and HCV RNA tests can 
conclusively rule out presence of active infection requiring therapy with Hepatitis B and C respectively. 
21 
 
 
 
  If any subject has a confirmed CR, PR, or SD after 2 years of study treatment, either tislelizumab or pamiparib or both agents can be stopped 
provided the study assessments and procedures are performed every 12 weeks with every radiographic tumor assessment. If a subject has evidence of PD 
within 1 year of treatment interruption, the Investigator can consider restarting the combined study treatment after discussion with the Sponsor, contingent 
on the continued availability of study medications.  The rationale for this change: a treatment hiatus for patients who have durable responses is allowed at the 
discretion of the treating investigator in consultation with the Sponsor.  The optimal duration of combined study treatment is not known, and a treatment 
hiatus may reduce patient burden. During the treatment hiatus, patients will be monitored with routine radiographic tumor assessments according to the 
protocol schedule and If there are indications of tumor progression, study treatment can be resumed. 
22  Tumor imaging (either computed tomography [CT] or magnetic resonance imaging [MRI], with preference for CT with contrast of chest, abdomen and 
pelvis, including bone scan for patients with bone metastasis) will be performed within 28 days prior to enrollment (bone scans can be within 56 days), and 
while on study approximately every 9 ± 1 week (calendar days) in the first 12 months and approximately every 12 ± 1 weeks thereafter. The same imaging 
technique should be used in a patient throughout the study. After the first documentation of response (CR or PR), imaging performed at the next regularly 

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scheduled time point will be used for response confirmation. Progressive disease suspected as pseudo-progression needs to be confirmed in a subsequent 
imaging at least 4 weeks later or at the next regularly scheduled time point but not to exceed 12 weeks, before discontinuation of study treatment. Patients 
who stop treatment prior to documentation of progressive disease will undergo repeated imaging for tumor response assessments as described in Section 
5.2.5.1. For patients with extensive-stage disease SCLC or patients with NSCLC, baseline brain MRI must be obtained, and will be repeated if brain 
metastases are noted at baseline as part of the assessment of anti-tumor activity during study treatment. 
23  Both tislelizumab and pamiparib treatments start from Cycle 1 Day 1. On Day 1 of each cycle, tislelizumab will be given intravenously after the morning 
dosing of pamiparib. See Section 6.2 for additional information regarding the administration of study drugs. If any subject has a confirmed CR, PR, or SD 
after 2 years of study treatment, either tislelizumab or pamiparib or both agents can be stopped provided the study assessments and procedures are performed 
every 12 weeks with every radiographic tumor assessment. If a subject has evidence of PD within 1 year of treatment interruption, the Investigator can 
consider restarting the combined study treatment after discussion with the Sponsor, contingent on the continued availability of study medications.  The 
rationale for this change: a treatment hiatus for patients who have durable responses is allowed at the discretion of the treating investigator in consultation 
with the Sponsor.  The optimal duration of combined study treatment is not known, and a treatment hiatus may reduce patient burden. During the treatment 
hiatus, patients will be monitored with routine radiographic tumor assessments according to the protocol schedule and If there are indications of tumor 
progression, study treatment can be resumed. 
24  Collection of archival tumor tissue for purpose of biomarker analysis. This is a mandatory requirement for patient enrollment and should be specified in the 
consent form. Specific instructions for tissue collection and shipment are provided in the Laboratory Manual. If tumor samples have been collected at pre-
screening stage, there is no need to collect it again during Screening.  
25  Archival tumor tissue will be collected for evaluation of potential biomarkers, although a fresh baseline tumor biopsy (within 12 weeks of starting treatment) 
is recommended. In the absence of archival tumor tissue, a fresh baseline biopsy of an accessible tumor lesion is mandatory, unless previously discussed 
with the sponsor’s medical monitor or its designee. For those patients who consent to fresh biopsy, an optional biopsy for biomarker analysis during the third 
week of the first cycle is recommended. For the patients who have confirmed disease progression, an optional biopsy may be taken at the Safety Follow-up 
visit.  The purpose of this biopsy sample is to evaluate mechanisms of resistance to the study treatment(s). If feasible, any follow up biopsy should be ideally 
taken from the same anatomical location as the baseline biopsy. Additional written patient consent is required for optional fresh tumor biopsies. Fresh 
biopsies should be limited to readily accessible tumor lesions (eg, skin; peripheral lymph nodes; and lung, liver or internal lymph node metastases which can 
be readily accessed using CT guidance). If performed, a tissue cylinder should be obtained that has proper size for histological examination and biomarker 
analysis. 
26  A blood sample at Screening stage will be collected for all patients in Part B, regardless of tumor type, for BRCA and/or other mutational analysis, even if it 
has been previously tested. 
27  
 
 
 
28  Patients who are suspected or known to have serious/severe respiratory conditions or exhibit significant respiratory symptoms unrelated to the underlying 
cancer will have pulmonary function testing which may include but is not limited to spirometry and assessment of diffusion capacity done during the 
Screening period to assist the determination of suitability on the study. These tests may include, but are not limited to, forced expiratory volume in 1 second 
(FEV1), forced vital capacity (FVC), diffusing capacity (DLCO), and FEV1/FVC.   
 
 

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2. Except for pre-dose PK, each PK sampling time point of tislelizumab and pamiparib will be in correspondence with the end of dosing of each agent, 
respectively. 
3. Triplicate ECG recordings (3 readings in rapid succession and not more than 2 minutes apart) will be obtained locally at the site in conjunction with blood 
sampling for pharmacokinetics of pamiparib. 
4. Tislelizumab PK samples will be collected at the same time points when the ADA samples are collected to assess the neutralizing capacity of ADA. Blood 
for anti-tislelizumab antibodies should be collected within 24 hours before the start of the first dose of tislelizumab in Cycle 1 and one sample prior to 
dosing between Day 7 through 10 in Cycle 1, and Day 1 of Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9 and Cycle 17. 
5. Within 2 hours prior to dosing. 
6. A window period of ± 10 minutes exists for all procedures. 
7. A window period of ± 30 minutes exists for all procedures occurring after the study drug is taken. Assessment to be performed 4 hours after the end of the 
infusion.  
 

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5.1.4 Dose Modifications, Dose Delay, and Missing Dose 
There will be no dose reduction of tislelizumab in this study. Dose delays of < 12 weeks will 
be permitted.  The Investigator should make every effort to maintain dose intensity in patients. 
Patients may temporarily suspend study treatment if they experience a toxicity that is 
considered related to tislelizumab and requires that a dose be withheld. Patients should resume 
tislelizumab treatment as soon as possible after the AE recovers to baseline or Grade 1 severity 
(whichever is more severe) within 12 weeks after the last dose of tislelizumab. If the patient is 
unable to resume tislelizumab in that timeframe, study treatment should be discontinued. 
If any subject has a confirmed CR, PR, or SD after 2 years of study treatment, either 
tislelizumab or pamiparib or both agents can be stopped provided the study assessments and 
procedures are performed every 12 weeks with every radiographic tumor assessment. If a 
subject has evidence of PD within 1 year of treatment interruption, the Investigator can 
consider restarting the combined study treatment after discussion with the Sponsor, contingent 
on the continued availability of study medications. 
The rationale for this change: a treatment hiatus for patients who have durable responses is 
allowed at the discretion of the treating investigator in consultation with the Sponsor.  The 
optimal duration of combined study treatment is not known, and a treatment hiatus may reduce 
patient burden. During the treatment hiatus, patients will be monitored with routine 
radiographic tumor assessments according to the protocol schedule and If there are indications 
of tumor progression, study treatment can be resumed. 
The Investigator should try his/her best to assess whether an adverse event is possibly related 
to tislelizumab only or pamiparib only or both, and treat the patient accordingly.  
In general dose delays for reasons other than management of AEs are discouraged. A dose 
delay of ≤ 21 consecutive days for pamiparib or a dose delay of ≤ 42 consecutive days for 
tislelizumab is allowed under the following guidance and at the discretion of the investigator 
after consultation with the sponsor or its designee. 
For tislelizumab, please refer to Appendix 10 for guidance for the management of irAEs 
including dose interruption and discontinuation. 
In case a patient is benefiting from the study treatment while meeting the discontinuation 
criteria, continuation of study treatment may occur upon discussion and agreement with 
Sponsor Medical Monitor. 
If the timing of a protocol-mandated study visit coincides with a holiday, weekend, or other 
event, the visit should be scheduled on the nearest feasible date (refer to the visit window in 

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Table 3 and Table 5), with subsequent dosing continued on the 21-day intervals afterward, with 
a minimum of 14 days between tislelizumab dosing. 
For pamiparib, please refer to Appendix 11 for dose interruption and/or modification of 
pamiparib. Pamiparib may be dose-reduced or delayed to manage unacceptable toxicity. In 
Part B of this study, dose reductions to pamiparib 20 mg orally twice daily are allowed. If the 
patient cannot tolerate pamiparib 20 mg orally twice daily, it should be discontinued. 
Pamiparib treatment can be held during management of AEs, according to Appendix 11. Any 
dose increase after dose reduction should be agreed upon between and investigator and the 
sponsor or its designee. 
If a dose is missed on any day for any reason, then it should not be made up and the patient 
should remain on their normal schedule.   
If a dose is delayed for pamiparib, the patient can continue tislelizumab dosing every 21 days 
and can resume pamiparib at any time. If a dose is delayed for tislelizumab for ≤ 10 days for a 
planned dosing cycle (eg, Cycle 3 Day 1), tislelizumab should be administered and all 
assessments should be conducted according to the original cycle (ie, Cycle 3); if the delay is 
more than 10 days, the patient should skip tislelizumab dose, and tislelizumab will be 
administered on Day 1 of the next planned cycle (ie, Cycle 4 Day 1). Patients who experience 
AE related to one investigational agent may continue treatment with the other investigational 
agent according to the protocol schedule after consultation with the sponsor or its designee. 
If tislelizumab cannot be resumed within 42 consecutive days of last dose due to tislelizumab 
treatment-related events, or if corticosteroid dose for an irAE is not able to be reduced to 
≤ 10 mg prednisone or equivalent per day by the end of 42 days’ dose interruption, the patient 
should be discontinued from tislelizumab, and continue pamiparib monotherapy once the irAE 
is resolved. If pamiparib cannot be resumed within 21 consecutive days of the last dose due to 
pamiparib treatment-related events, pamiparib will be permanently discontinued and the 
patient may continue tislelizumab monotherapy alone. Exemptions may be considered for 
those patients who are determined by the investigator to have received clinical benefit and it is 
considered safe and to be in the best interest of the patient to resume the treatment after 
consultation with the sponsor or its designee. 
Palliative radiation to existing sites of metastatic disease to alleviate the tumor obstruction 
and/or pain will be allowed provided tislelizumab dosing does not occur within 1-week pre- or 
post-radiation. Pamiparib should be held 3 days before and resume 3 days after completion of 
radiation. Patients who require palliative radiotherapy to manage the symptoms of progressive 
disease should be discontinued. Any exception will need to be discussed with and agreed by 
the sponsor’s medical monitors.  

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5.1.5 Treatment beyond Progression 
In the absence of unacceptable toxicity, patients may continue with administrations of the 
combination of tislelizumab and pamiparib at the same dose unless a dose interruption or 
modification is required based on the guidance described below, or at the discretion of the 
investigator after consultation with the sponsor or its designee. The patients with disease 
progression that the investigator considers to be consistent with “pseudo-progression” will be 
allowed to continue the study drug treatment of pamiparib alone or tislelizumab alone or the 
combination of tislelizumab and pamiparib if the patient is benefiting from the treatment in the 
judgment of the investigator after consultation and agreement with the sponsor’s medical 
monitor or its designee.  The criteria for pseudo progression will not be met if the only change 
is reflected in tumor markers, such as CA-125 or PSA.  
If pseudo-progression is suspected, the patient will be allowed to continue study treatment if 
they meet all of the following criteria: 
 Investigator-assessed benefit 
 Patient is tolerating study drug(s) and agrees to continue study treatment 
 Stable (ie, not deteriorating) Eastern Cooperative Oncology Group (ECOG) performance 
status 
 Absence of rapid progression of disease or of progressive tumor at critical anatomic sites 
(eg, spinal cord compression) that necessitates urgent alternative medical intervention 
 The patient must be reconsented to continue study treatment  
5.2 
Selection of Study Population 
5.2.1 Inclusion Criteria 
Patients may be enrolled in the study only if they meet all the following criteria: 
1. Patients have voluntarily agreed to participate by giving written informed consent. 
2. Patients must have received standard of care in the primary treatment of their disease. 
3. Patients who have the below specified histologically confirmed malignancies that have 
progressed to the advanced or metastatic stage. 
a) In Part A, the patients must have an advanced malignancy including but not limited to 
high-grade serous cancer of the ovary, fallopian tube, or peritoneum, triple negative 
breast cancer, SCLC, primary peritoneal cancer, and any tumor likely to harbor DNA 

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damage repair deficiencies susceptible to treatment with a PARP inhibitor or likely to 
be responsive to a PD-1 blocker. 
b) In Part B, the patients recruited to one of the eight expansion arms must have advanced 
solid tumors of the following types: 
Arm 1: Patients with relapsed, platinum-sensitive high grade epithelial, non-mucinous, 
ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) must meet the 
following criteria: 
i. 
Patients must have at received least 2 prior platinum-containing treatments in 
any treatment setting. 
 Note: patients may have received additional therapy after the last 
platinum-containing line of treatment if the other eligibility criteria are 
met. 
ii. 
Patients must have platinum-sensitive recurrent disease and must not have 
progressed (by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1 
criteria) within 6 months of the completion of the last platinum-containing 
line of treatment.  
 Note: patients may receive additional non-platinum based chemotherapy 
for recurrence after the prior platinum-containing line of treatment if the 
criteria for platinum-sensitivity are met. 
iii. 
Arm 1a: Known deleterious or suspected deleterious germline or somatic 
BRCA1/2 mutations or with HRD. 
 If HRD or BRCA1/2 mutation status from archival tissue is unknown or 
has not been previously evaluated, then the archival tissue must undergo 
tissue screening using a validated diagnostic test to determine eligibility. 
If the diagnostic test result is BRCA1/2 or HRD positive the patient will 
be eligible for enrollment in Arm 1a. 
iv. 
Arm 1b: Without known germline or somatic BRCA1/2 mutations and 
without HRD mutation. 
Arm 2: Patients with triple negative breast cancer must meet the following criteria: 
i. 
Patients with 0-1 prior platinum-containing treatment in any treatment 
setting. 
 Note: patients could have received additional therapy after the last 
platinum-containing line of treatment if the other eligibility criteria are 
met. 
ii. 
Patients who have received at least 1 but no more than 3 prior lines of 
treatment in the advanced or metastatic setting.. 
iii. 
Known deleterious or suspected deleterious germline or somatic BRCA1/2 
mutations or with documented HRD.  

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 If HRD or BRCA1/2 mutation status from archival tissue is unknown or 
has not been previously evaluated, then the archival tissue must undergo 
tissue screening using a validated diagnostic test to determine eligibility. If 
the diagnostic test result is HRD positive, then the patient will be eligible 
for enrollment in Arm 2. 
 If archival tissue is not available and the patient submits a fresh tumor 
biopsy, then the diagnostic test needs to demonstrate somatic BRCA1/2 
mutation or HRD positivity. 
Arm 3: Patients with metastatic castration-resistant prostate cancer, including but not 
limited to mutations in HR pathways and/or defined by HRD algorithms, and 
must meet the following criteria: 
i. 
The patient may be either chemotherapy-naïve, but must have received prior 
abiraterone acetate and/or enzalutamide treatment, or have previously had no 
more than 2 taxane-based chemotherapy lines of treatment including 
docetaxel and carbazitaxel. If docetaxel is used more than once, this will be 
considered as 1 line of treatment. 
ii. 
At least 2 weeks since the completion of prior flutamide, bicalutamide, and 
nilutimide, or enzalutamide and abiraterone treatment. 
iii. 
Documented prostate cancer with one of the following: 
 Surgically or medically castrated. The testosterone levels do not need to be 
checked if the patient has undergone surgical castration for > 4 months. 
Patients receiving chemical castration should have testosterone levels 
checked at baseline and confirmed to be in the castrate levels (< 0.5 ng/mL 
or 1.735 nM). In all cases the luteinizing hormone-releasing hormone 
(LHRH) antagonist/agonist is to be continued in these patients. 
 Patients with only non-measurable bone lesions must have disease 
progression based on PCWG3 with 2 or more new lesions or have 
prostate-specific antigen (PSA) progression before enrollment. 
iv. 
Known deleterious or suspected deleterious germline or somatic BRCA1/2 
mutations or with documented HRD.  
 If HRD or BRCA1/2 mutation status from archival tissue is unknown or 
has not been previously evaluated, then the archival tissue must undergo 
tissue screening using a validated diagnostic test to determine eligibility. If 
the diagnostic test result is HRD positive, then the patient will be eligible 
for enrollment in Arm 3. 
 If archival tissue is not available and the patient submits a fresh tumor 
biopsy, then the diagnostic test needs to demonstrate somatic BRCA1/2 
mutation or HRD positivity. 
Arm 4: Patients with extensive-stage disease small cell lung cancer (SCLC) must meet 
the following criterion: 
i. 
Patients received at least 1 but no more than 2 prior lines of treatment. 

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ii. 
At least 1 prior treatment for must have contained a platinum agent 
Arm 5: Patients with HER2-negative gastric or gastroesophageal junction cancer must 
meet the following criteria: 
i. 
Received at least 1 but no more than 2 prior lines of treatment. 
ii. 
 
Arm 6: Patients with locally advanced or metastatic urothelial (muscle-invasive bladder, 
ureter, urethra or renal pelvis) cancer must meet the following criteria: 
i. 
At least 1 but no more than 2 prior lines of treatment in the advanced or 
metastatic disease setting. 
ii. 
At least 1 prior treatment must have contained a platinum agent. 
Arm 7: Patients with advanced or metastatic pancreatic adenocarcinoma must meet the 
following criteria: 
i. 
At least 1 prior treatment for advanced or metastatic disease  
ii. 
At least 1 prior treatment must have contained a platinum agent 
iii. 
Patients with known deleterious germline or somatic BRCA1/2 mutations can 
be considered for the study even if platinum-naïve.  
Arm 8: (NOTE: CLOSED TO ENROLLMENT) Patients with advanced or metastatic 
recurrent non-ovarian gynecological cancers (endometrial cancer, cancer of the 
cervix and patients with tumors known to be MMR deficient or HRD positive) 
must meet the following criteria: 
i. 
Patients with a complete response, partial response or stable disease from at 
least 1 prior platinum-containing treatment in any treatment setting. 
ii. The Sponsor medical monitor will approve tumor types for Arm 8 prior to 
screening. 
 Note: Excluded tumor types include patients with bone or soft tissue 
sarcoma; central nervous system (CNS) malignancies; colorectal cancer 
(except microsatellite instability-high [MSI-H] colorectal cancer is 
permitted); cutaneous or ocular melanoma; hematologic malignancies; 
HER2-negative breast cancer without BRCA mutation; mesothelioma, 
papillary, follicular, medullary or Hürthle cell thyroid cancer; unknown 
primary malignancy. 
4. Patients who were treated with chemotherapy or any investigational therapies, if eligible, 
must have been completed at least 4 weeks or at least 5 half-lives (whichever is longer, but 
no less than 3 weeks) before the study drug administration, and all AEs have either returned 
to baseline or stabilized.  
5. At least 2 weeks from palliative radiotherapy. 

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6. Patients must have archival tumor tissue or agree to a tumor biopsy for biomarkers analysis 
unless previously discussed with sponsor’s medical monitor or its designee (fresh tumor 
biopsies are recommended at baseline in patients with readily accessible tumor lesions who 
can safely undergo the procedure and who consent to the biopsies). Patients with ovarian, 
fallopian tube, primary peritoneal, or breast cancer in Part A and all patients enrolled in 
Part B must also agree to provide fresh blood sample at the baseline for the evaluation of 
BRCA mutations and/or confirmation of prior BRCA results or other homologous 
recombination deficiency mutations even if it was previously tested. 
7. Patients must have measurable disease as defined in RECIST v1.1. Patients with metastatic 
castration-resistant prostate cancer and epithelial, non-mucinous, ovarian cancer, fallopian 
tube, or primary peritoneal cancer may use separate disease-specific criteria (see 
Appendix 4, Appendix 6, and Appendix 8). 
8. Patients must be a male or female ≥ 18 years of age on the day of signing informed consent. 
9. Patients must have an ECOG Performance Status (PS) ≤ 1 (Appendix 3). 
10. Patients must have a life expectancy ≥ 12 weeks. 
11. Patient must have adequate organ function as indicated by the following laboratory values 
independent of transfusion within 2 weeks: 
a) Absolute neutrophil count (ANC) ≥ 1,500/mL. 
b) Platelets ≥ 100,000/mL. 
c) Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L. 
d) Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 by Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI) equation (Appendix 18). 
e) Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) (On fractionation ≤ 90% of 
total bilirubin should be unconjugated. Total bilirubin must be < 4 X ULN for patients 
with Gilbert’s syndrome). 
f) 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]) and 
alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 × ULN.  
g) International normalized ratio (INR) ≤ 1.5 × ULN (≤ 2.5 × ULN if on anticoagulants).  
12. Females of childbearing potential must be willing to use a highly effective method of birth 
control for the duration of the study (Appendix 17), and for at least 6 months after the last 
dose of investigational drug, and have a negative serum pregnancy test within 7 days of the 
first dose of study drug(s). 

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13. Non-sterile males and their female partners must be willing to use a highly effective 
method of birth control for the duration of the study and for at least 6 months after the last 
dose of investigational drug (see Appendix 17). Nonsterile males must avoid sperm 
donation for the duration of the study and for at least 6 months after last study drug. 
14. Female patient must agree not to breastfeed starting at screening and throughout the study 
period, and for 6 months after the final study drug administration.  
5.2.2 Exclusion Criteria 
Patients will not be enrolled in the study for any of the following reasons: 
1. Patients with ovarian cancer who have platinum-resistant/refractory disease, defined as 
progressive disease at the first RECIST v1.1 tumor assessment while receiving 
platinum-containing chemotherapy. 
2. Patient has history of severe hypersensitivity reactions to other monoclonal antibodies 
(mAbs). 
3. Any major surgery within 28 days before first dose of study drugs. 
4. Prior allogeneic stem cell transplantation or organ transplantation. 
5. Patients with toxicities (as a result of prior anticancer therapy) which have not recovered 
to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, 
neuropathy and specific laboratory abnormalities). 
6. Concurrent participation in another clinical trial. 
7. Prior malignancy within the previous 2 years except for locally curable non-melanoma 
dermatologic cancers that have been treated with curative intent and are at very low risk 
for recurrence, such as basal or squamous cell skin cancer, or carcinoma in situ of the skin, 
cervix, breast, bladder, or prostate. 
8. Symptomatic CNS metastasis or leptomeningeal disease. 
Note: Baseline MRI of the brain and spinal cord is required for SCLC patients enrolled 
in Arm 4  
Note: Patients with previously treated CNS metastatic disease are eligible for any arm 
if CNS metastatic disease is asymptomatic, clinically stable, and does not require 
corticosteroids or anticonvulsants within a minimum of 4 weeks of enrollment. 
9. Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or PARP.  

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10. Active autoimmune diseases or history of autoimmune diseases that may relapse 
(Appendix 15).  
Note: Patients with the following diseases are not excluded and may proceed to further 
screening:  
a) Controlled Type I diabetes. 
b) Hypothyroidism managed with no treatment other than with hormone replacement 
therapy. 
c) Controlled celiac disease. 
d) Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia). 
e) Any other disease that is not expected to recur in the absence of external triggering 
factors. 
11. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily 
of prednisone or equivalent) or other immunosuppressive medication within 2 weeks of the 
study drug administration. 
Note: Patients who are currently or have previously been on any of the following steroid 
regimens are not excluded: 
a) Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent).  
b) Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with 
minimal systemic absorption. 
c) Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for 
contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, 
delayed-type hypersensitivity reaction caused by contact allergen). 
12. With severe chronic or active infections requiring systemic antibacterial, antifungal or 
antiviral therapy, including tuberculosis infection, etc.  
13. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled systemic 
diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung diseases, etc. 
14. History of non-viral hepatitis or cirrhosis. 
15. Positive human immunodeficiency virus (HIV) status. 
16. A known history of hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. 
17. History of alcohol abuse. 

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18. Underlying medical conditions or alcohol or drug abuse or dependence that, in the 
investigator’s opinion, will be unfavorable for the administration of study drug or affect 
the explanation of drug toxicity or adverse events; or insufficient compliance during the 
study according to investigator’s judgement. 
19. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, 
crushing, opening or otherwise altering the product formulation. Patients should not have 
gastrointestinal illnesses that would preclude the absorption of pamiparib, which is an oral 
agent. Please note Appendix 12 for a list of prohibited medications that are associated with 
possible interactions with pamiparib.  
20. Has been administered a live vaccine within 4 weeks (28 days) of initiation of study 
therapy.  Patients are eligible if 28 days have elapsed since receipt of vaccine and initiation 
of study treatment.  (NOTE: seasonal vaccines for influenza are generally inactivated 
vaccines and are allowed.  Intranasal vaccines are live vaccines; and are not allowed). 
21. Any of the following cardiovascular criteria: 
a) Current evidence of cardiac ischemia. 
b) Current symptomatic pulmonary embolism. 
c) Acute myocardial infarction ≤ 6 months prior to Day 1. 
d) Heart failure of New York Heart Association Classification III or IV (see Appendix 16) 
≤ 6 months prior to Day 1. 
e) Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to Day 1. 
f) History of cerebrovascular accident within 6 months before first dose of study drugs. 
22. Use or have anticipated need for food or drugs known to be strong or moderate cytochrome 
P450 (CYP)3A inhibitors or strong CYP3A inducers ≤ 10 days (or ≤ 5 half-lives, 
whichever is shorter) prior to Day 1 (Appendix 12). 
5.2.3 Other Eligibility Criteria Considerations 
To assess any potential impact on the patient eligibility with regard to safety, the investigator 
must refer to the IB for detailed information regarding warnings, precautions, 
contraindications, AEs, and other significant data pertaining to the investigational product 
being used in this study. [12, 19] Any patient in this study who continues to demonstrate 
objective clinical benefit at the end of a 2-year treatment duration may continue in the study or 
on treatment. 

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5.2.4 Patient Restrictions 
The following restrictions may affect patient participation in this study: 
 The investigator must be informed as soon as possible (ASAP) about any medications 
or other study agents taken from the time of screening until the patient is discharged 
from the study. 
 Consumption of grapefruit and Seville oranges or their juices are not allowed 
throughout the study. No other dietary restrictions will apply. 
5.2.5 Patient Discontinuation and Withdrawal 
Patients may withdraw at any time or be discontinued from the study at the discretion of the 
investigator should any untoward adverse effects occur. In addition, a patient may be 
withdrawn by the investigator or the sponsor if he/she violates the study plan or for 
administrative and/or other safety reasons. The investigator or study coordinator must notify 
the sponsor immediately when a patient has been discontinued/withdrawn due to an adverse 
event. When a patient discontinues/withdraws, all applicable evaluations scheduled for the 
final study visit should be performed at the time of discontinuation. Any adverse event which 
is present at the time of discontinuation/withdrawal should be followed in accordance with the 
safety requirements outlined in Section 8.4. 
In the event that a patient is prematurely discontinued from the study at any time due to an AE 
(as defined in Section 10.3), the procedures stated in Section 8.5 must be followed. 
In addition to the post-study assessments, if a DLT occurs, the investigator will obtain, when 
possible, a blood sample for analysis of serum tislelizumab and plasma pamiparib 
concentration. 
Patients who discontinue or are withdrawn for any reason other than DLT during Cycle 1 of 
any DL will be considered for replacement after due consideration by the sponsor and/or SMC 
if the minimum number of patients needed for the evaluation of MTD is not met. 
Premature discontinuation of tislelizumab and pamiparib would be any time when a patient is 
discontinued for reasons other than unacceptable toxicity. The reason for discontinuation of 
the study drugs will be recorded in the electronic case report form (eCRF). These reasons may 
include: 
 Withdrawal of consent by the patient; 
 Discontinuation of tislelizumab/pamiparib by the sponsor; 
 Pregnancy; 
 Any significant AE that compromises the patient’s ability to participate in the study; 

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 The investigator or sponsor determines it is in the best interest of the patient; 
 Death;  
 Lost to follow up; 
 Confirmed progression of disease at any time during the study (refer to Section 8.8.1); 
 Significant deviation from the protocol by the investigator without the consent of the 
sponsor. 
5.2.5.1 Patients Withdraw Prior to Documentation of Progressive Disease 
Patients who stop treatment prior to documentation of progressive disease (PD) will undergo 
repeated imaging for tumor response assessments during the study approximately every 
9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks thereafter until 
unequivocal PD is documented or the patient starts new anticancer therapies or patient 
withdraws consent from the trial. This imaging schedule will be maintained and will never be 
adjusted regardless of any intermediate unscheduled scans. Patients who withdraw from the 
study for clinical or symptomatic deterioration before objective documentation of PD will be 
requested to undergo appropriate imaging to confirm PD. Every effort will be made to confirm 
a clinical diagnosis of PD by imaging. 

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6.0 STUDY TREATMENTS 
6.1 
Description of Investigational Product 
Tislelizumab is a monoclonal antibody drug which is formulated for IV injection in a single-
use vial (20R glass, USP type I) containing a total of 100 mg antibody in 10 mL of isotonic 
solution. See Section 6.5 below for handling and product storage conditions. 
Refer to the IB for more detailed information on the product description for tislelizumab. [12] 
The patients will receive pamiparib as 10 mg or 40 mg 
 capsules, depending on dose 
level and availability (
 capsules for 
 mg dose and s
 
 capsules for 
 mg dose).  BGB-290 drug product is also supplied as a 
mg strength 
in 
capsules (
 capsule shells). 
Refer to the IB for more detailed information on the product description for pamiparib. [19]  
6.2 
Dosage and Administration 
The treatments to be administered during the study are: 
 Tislelizumab 10 mL single-use vial for IV infusion 
 Pamiparib 10 mg, 20 mg, and 40 mg capsules for oral use 
Tislelizumab will be administered as an IV infusion, every 3 weeks. Pamiparib will be 
administered orally twice daily, once in the morning and once in the evening 12 hours apart. 
The starting dose of each agent will not exceed the highest DL at which no DLT was reported 
during the first-in-human ongoing trials. 
In both Parts A and B of the study, tislelizumab will be administered as an IV infusion on Day 
1 of a 21-day cycle, and pamiparib will be taken orally twice daily starting from Day 1.  
On the first day where both study drugs are administered, the morning dose of pamiparib 
should be given at least 30 minutes prior to the IV infusion of tislelizumab. Subsequently in 
the evening, pamiparib administration is repeated. On subsequent days of each cycle, twice 
daily dosing of pamiparib will continue in the morning and evening (at approximately the same 
time), as a 20-day period of continuous drug administration. During subsequent cycles, the 
treatment repeats every 21 days for 34 cycles (2 years) from Day 1 to Day 21.  
If a dose of pamiparib is not taken at the scheduled time, it can be taken ASAP within 2 hours 
of the scheduled time and return to the normal schedule for the next dose. Extra dose of 
pamiparib should not be taken to make up for the missed dose.  Patients will be instructed to 
swallow the capsules whole, in rapid succession, with water. Pamiparib can be administered 
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Tislelizumab will be administered by IV infusion through an intravenous line containing a 
sterile, non-pyrogenic, low-protein binding 0.2 micron in-line or add-on filter. Specific 
instructions for product preparation and administration are provided in the Pharmacy Manual. 
As a routine precaution, after infusion of tislelizumab on day 1 of cycle 1 and cycle 2, 
patients must be monitored for at least 1 hour afterwards in an area with resuscitation 
equipment and emergency agents.  From cycle 3 onward, at least a 30-minute monitoring 
period is required in an area with resuscitation equipment and emergency agents. 
The initial infusion (cycle 1, day 1) will be delivered over 60 minutes; if this is well 
tolerated, then the subsequent infusions may be administered over 30 minutes, which is the 
shortest time period permissible for infusion.  Tislelizumab must not be concurrently 
administered with any other drug (refer to Section 7.0). 
Guidelines for dose modification, treatment interruption, or discontinuation and for the 
management of irAEs and infusion-related reactions are provided in detail in Section 10.13.4 
and Appendix 10.  
Refer to the Pharmacy Manual for detailed instructions on drug preparation, storage, and 
administration. 
For management of toxicity refer to Section 5.1.4. 
6.3 
Patient Identification 
Patients will be identified by a patient number. Each patient enrolled in this study will receive 
a unique patient number after signing the informed consent. 
Each patient receiving concomitant tislelizumab and pamiparib will also receive a treatment 
allocation number. Patient and treatment numbers will be assigned in chronological order 
starting with the lowest number. Once a patient number and treatment number have been 
assigned to a patient, it cannot be reassigned to any other patient. 
If a patient is replaced, the replacement patient will be assigned the next available patient 
number. 
6.4 
Packaging and Labeling 
Tislelizumab has been aseptically filled in 20R glass vials with a Flurotec-coated butyl rubber 
stopper and an aluminum cap. Each vial contains 10 mL of the drug solution. The vials are 
packaged in cartoon box. 
The capsule supplies of pamiparib will be provided in a child-resistant closure and be 
open-labeled with space to enter the patient’s treatment number and period number. 

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The primary labeling on the tislelizumab vials and pamiparib child-resistant closure contain 
following information: protocol number, content and quantity of study drugs, batch number, 
expiry date, storage instructions, and administration instructions. The contents of the label will 
be in accordance with all applicable regulatory requirements. 
6.5 
Handling and Storage 
The investigational products will be dispatched to a study center only after receipt of the 
required documents in accordance with applicable regulatory requirements and the sponsor’s 
procedures. 
Investigational products must be dispensed or administered according to procedures described 
herein. Only patients enrolled in the study may receive investigational products, in accordance 
with all applicable regulatory requirements. Only authorized study center personnel may 
supply or administer investigational products. All investigational products must be stored in a 
secure area with access limited to the investigator and authorized study center personnel and 
under physical conditions that are consistent with investigational product-specific 
requirements. The investigational products, tislelizumab vials must be kept at 2oC to 8oC and 
pamiparib capsules must be kept at 15oC to 30°C. 
Tislelizumab does not contain a preservative. The diluted solutions of tislelizumab cannot be 
frozen, and must be stored at: 
 Either room temperature at 20°C to 25°C (68°F to 77°F) for no more than 4 hours from the 
time of reconstitution. This includes room temperature storage of tislelizumab vials, 
storage of the infusion solution in the IV bag, and the duration of infusion. 
 Or under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from the 
time of reconstitution. If refrigerated, allow the diluted solution to come to room 
temperature prior to administration. 
6.6 
Product Accountability 
The investigator is responsible for investigational products accountability, reconciliation, and 
record maintenance. In accordance with all applicable regulatory requirements, the investigator 
or designated study center personnel must maintain investigational products accountability 
records throughout the course of the study. This person(s) will document the amount of 
investigational products received from the sponsor, the amount supplied and/or administered 
to and returned by patients, if applicable. 

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After completion of the study, all unused investigational products will be inventoried and 
packaged for return shipment by the hospital unit pharmacist. The inventoried supplies will be 
returned to the sponsor or destroyed on site, after receiving written sponsor approval. 
6.7 
Assessment of Compliance 
On all visits to the study center, patients will be questioned in regard to compliance with study 
instructions. 
The investigator and/or study personnel will keep accurate records of the quantities of capsules 
dispensed and used by each patient. This information must be captured in the source document 
at the end of each cycle. The investigator is responsible for pamiparib accountability, 
reconciliation, and record maintenance. In accordance with all applicable regulatory 
requirements, the investigator or designated study center personnel must maintain pamiparib 
accountability records throughout the course of the study. This person will document the 
amount of pamiparib received from the sponsor, the amount supplied, and/or administered to 
and returned by patients, if applicable. 
6.8 
Treatment of Investigational Product Overdose 
Any overdose or incorrect administration of study drug should be noted in the patient’s chart 
and on the appropriate eCRF.  AEs associated with an overdose or incorrect administration of 
study drug will be recorded on the adverse event eCRF.  If an overdose or incorrect 
administration of study treatment takes place, the sponsor or designee is required to be notified 
as soon as possible. Supportive care measures should be administered as appropriate. 
6.9 
Medical Care of Patients after the End of Trial 
After a patient has discontinued from the study, other treatment options decided by the treating 
physician may be implemented, if required, in accordance with the investigational site’s 
common medical practice and depending on the patient’s individual medical needs. 
6.10 Occupational Safety 
The investigational products are not expected to pose significant occupational safety risk to the 
study center personnel under normal conditions of use and administration. A material safety 
data sheet describing occupational hazards and recommended handling precautions will be 
provided to the investigator, where this is required by local laws, or is available upon request 
from the sponsor. 

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7.0 CONCOMITANT 
MEDICATIONS 
AND 
NON-DRUG 
THERAPIES 
7.1 
Permitted Medications 
All treatments that the investigator considers necessary for a patient’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care. All concomitant medications taken during the study will be recorded on the case 
report form (CRF) including all prescription, over-the-counter (OTC), herbal medicines, 
mushroom-containing products, dietary supplements and IV medications and fluids. If changes 
occur during the study period, documentation of drug dosage, frequency, route, and date will 
also be included on the CRF. 
All concomitant medications received within 30 days before the first dose of study medication 
and 30 days after the last dose of study medication should be recorded. 
The eCRF entry must include the dose, regimen, route, tumor type, and start and stop dates of 
use of the prior and concomitant medication. 
7.2 
Prohibited Medications 
Patients may receive other medications that the investigator deems to be medically necessary, 
with the specific exception of non-protocol specified chemotherapy, therapeutic radiotherapy, 
immunotherapy, anti-neoplastic biological therapy or investigational agents other than 
tislelizumab and pamiparib. External beam radiation therapy is allowed only for those patients 
who require radiation therapy for the treatment of pain secondary to bone metastases. Radiation 
therapy provided for therapeutic intent will be considered anticancer treatment. Patients who 
in the assessment by the investigator require the use of any of the aforementioned treatments 
for clinical management should be removed from the study. Bisphosphonate or denosumab use 
is permitted if the patient has already been on it for 3 or more months and on a stable dose. 
Patients with active autoimmune disease or history of autoimmune disease that might recur, or 
who require immune suppressive treatment including systemic corticosteroids, should be 
excluded. These include but are not limited to patients with a history of immune-related 
neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-
Barre syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue diseases, 
scleroderma, inflammatory bowel disease, Crohn’s, ulcerative colitis, hepatitis, TEN, Stevens-
Johnson syndrome, or anti-phospholipid syndrome. 
Patients are prohibited from receiving any live vaccines within 4 weeks (28 days) of initiation 
of study therapy.  Patients are eligible if 28 days have elapsed since receipt of vaccine and 

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initiation of study treatment.  (NOTE: seasonal vaccines for influenza are generally inactivated 
vaccines and are allowed.  Intranasal vaccines are live vaccines; and are not allowed.) 
The primary metabolic pathway for pamiparib involves the cytochrome P450 (CYP)3A 
isoform. The compounds/substances presented in Appendix 12 are associated with possible 
interactions with pamiparib through the CYP3A metabolic pathway as well as other various 
metabolic interactions and are prohibited. [85] 
Preliminary in vitro screening assays revealed pamiparib is not a strong inhibitor of human 
CYP isoenzymes tested. It is a moderate inhibitor of CYP2C9 (IC50 = 6.48 M). Patients taking 
the medications presented in Appendix 13 need to be closely monitored for AEs. [85] 
In addition to CYP3A and CYP2C9, pamiparib can also be metabolized by CYP2C8 in human 
liver microsomes, but to a lesser extent. The compounds/substances presented in Appendix 14 
are associated with possible interactions with pamiparib through the CYP2C8 metabolic 
pathway and should also be used with caution. [85] The following website can be used as an 
alternate reference: medicine.iupui.edu/clinpharm/ddis 
The potential for drug-drug interaction between tislelizumab and small-molecule drug products 
is very low, given tislelizumab is a therapeutic monoclonal antibody.  Because tislelizumab is 
expected to be degraded into amino acids and recycle into other proteins, it is unlikely to have 
an effect on drug metabolizing enzymes or transporters. 
Section 5.2.2 of the protocol (Exclusion Criteria) describes other medications which are 
prohibited in this study.  
7.2.1 Other Study Considerations 
The following nondrug therapies must not be administered during the study (within 28 days 
before the start of study treatment): 
 Major surgery (excluding prior diagnostic biopsy) 
 Herbal remedies with immune-stimulating properties (ie, mistletoe extract) or known 
to potentially interfere with major organ function (ie, hypericin). Alternative medicines 
for cancer therapy or for altering the immune system. 
 Drugs that are known to cause prolongation in QT/QTc interval and/or induce Torsades 
des Pointes (Appendix 17). 
 Patients should avoid alcohol consumption and should avoid any other drugs or 
supplements during the study not prescribed by the attending physician. 

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8.0 STUDY ASSESSMENTS 
8.1 
Prescreening (Part B Only) 
Patients in Arm 1 (ovarian cancer), Arm 2 (TNBC), and Arm 3 (mCRPC) in Part B of the study 
who have unknown biomarker status will be permitted to have a pre-screening period for HRD 
status. A separate pre-screening informed consent must be obtained for patients in these arms. 
An archival tumor sample will be obtained for pre-screening purpose for patients in Arm 1 
(ovarian cancer), Arm 2 (TNBC), and Arm 3 (mCRPC). If an archival tumor sample is not 
available, a fresh tumor biopsy of an accessible tumor lesion will be obtained for the pre-
screening purpose.  
The following will be performed during pre-screening tumor sample collection: 
 Obtain written informed consent from the patient or the patient’s legal representative 
to perform a tumor biopsy if it is required for the purpose of meeting the eligibility 
criteria of the study 
 Prepare tumor samples and ship to the qualified central laboratory for mutation 
analysis as specified in the Laboratory Manual 
Patients in Arm 1 (ovarian cancer) will proceed to the screening phase once they have signed 
the pre-screening informed consent and submitted their tumor tissue sample.  Their biomarker 
status does not preclude their eligibility while both Arm 1a and Arm 1b remain open and 
enrolling. When either Arm 1a or Arm 1b is 50% enrolled, then biomarker status must be 
determined prior to patients proceeding to the screening phase to avoid over-enrollment to the 
cohort. 
Patients in Arm 2 (TNBC) and Arm 3 (mCRPC) who submit archival tissue with proven 
mutational positivity are eligible for enrollment in Arm 2 or Arm 3.  If a diagnostic test result 
on submitted archival tissue is HRD negative or is a failure, then the patient is not eligible for 
enrollment.   
For patients in Arm 2 (TNBC) and Arm 3 (mCRPC) who submit a fresh tumor biopsy, their 
biomarker status will determine whether they will be eligible for enrollment in Arm 2 or Arm 
3, respectively.  If the pre-screening biopsy demonstrates germline or somatic BRCA1/2 
mutation or HRD positivity, then the patient would be eligible for enrollment in Arm 2 or Arm 
3.  If the results of the mutational test on the pre-screening biopsy is HRD negative or is a 
failure, then the patient is not eligible for enrollment. 
8.2 
Screening 
A signed, written informed consent must be obtained prior to screening assessments and before 
any study-specific assessments are initiated. The study-specific assessments and procedures 

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are shown in the study assessments and procedures schedule in Table 3 and Table 5. The PK 
sampling time points are presented in Table 4 and Table 6. 
The screening assessments are the same for Part A and Part B of the study.  
Re-screening of laboratory parameters which do not meet the specified inclusion criteria will 
be allowed once per patient within the screening period window (Day -28 to Day -1). 
Patients who are suspected or known to have serious/severe respiratory conditions or exhibit 
significant respiratory symptoms unrelated to the underlying cancer will undergo pulmonary 
function testing which may include but is not limited to spirometry and assessment of diffusion 
capacity done during the Screening period to assist the determination of suitability on the study 
(see Table 5). 
8.2.1 Demographic and Baseline Assessments 
Demographic and baseline assessments are the same for Part A and Part B. 
Demographic data will include gender, age or date of birth, race, and ethnicity. This data will 
be captured in the eCRF. 
Having given consent, patients will be required to undergo a medical screen to determine 
whether they are eligible to participate in the study according to the criteria listed in 
Section 5.2. Screening assessments will be completed within 28 days prior to the first dose of 
the investigational product. If screening laboratory tests are completed within 14 days prior to 
first dose, pre-dose samples on Day 1 of Cycle 1 will not be repeated. The screening 
assessments will include: 
 Baseline demographics 
 Medical history including date of first cancer diagnosis, histology, prior anti-neoplastic 
therapy, and current sites of disease (Section 8.3.3) 
 Concurrent medications, herbal medications, mushroom-containing products, and dietary 
supplements 
 Vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate, 
temperature, and respiratory rate) 
 Physical examinations, including height (in cm), body weight (in kg), and body mass index 
(in kg/m2) (NOTE: Body Mass Index will be collected in Part A only) 
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 Evaluation of AEs (After informed consent has been signed but prior to the administration 
of the study drug, only SAEs should be reported) 
 ECOG performance status (refer to Appendix 3) 
 12-lead electrocardiogram (ECG) within 14 days of Cycle 1 Day 1  
 Laboratory tests: complete blood count (CBC), and serum chemistry, including serum 
testosterone for prostate cancer patients; urinalysis; pregnancy test (within 7 days of the 
first investigational product administration), and PT/aPTT 
 Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), HCV antibody, 
HIV 1/2 antibodies, and HBV DNA and/or HCV RNA if needed.  Hepatitis E antibody or 
HEV RNA should be performed at baseline if testing is available. 
 
 
 
 
 
 
 CT/MRI scan will be performed within 28 days prior to the first administration of 
investigational product.  
o Bone scans will be performed within 56 days prior to the administration of 
investigational product. 
o Any patient with a history of CNS metastases will be required to undergo CT/MRI 
at baseline to ensure all sites of disease are evaluated per RECIST v1.1 criteria. 
Patients with newly diagnosed brain metastases on screening CT/MRI will be 
required to be treated for brain metastasis with standard of care treatments and be 
off corticosteroids prior to study entry. 
o All patients with SCLC are required to have CT/MRI of the brain at baseline 
 A blood sample must be collected at screening stage for ovarian, fallopian tube, primary 
peritoneal, and breast cancer patients for germline BRCA and/or other mutations analysis 
for patients enrolled in Part A. All patients in Part B, regardless of tumor type, will have 
blood drawn for BRCA and/or other mutational analysis, even if it has been previously 
tested. 
 Collection of archival tumor specimen or fresh tumor biopsy. If tumor samples have been 
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 
 
 
The above-mentioned data will be captured in the source documents. Any results falling 
outside the normal range will be repeated at the discretion of the investigator. 
8.2.2 Females of Childbearing Potential and Contraception 
See Appendix 17 for The Clinical Trials Facilitation Group’s recommendations related to 
contraception and pregnancy testing in clinical trials including the use of highly effective forms 
of birth control. 
8.3 
Assessments During Treatment 
Safety assessments should be performed at all visits to the study center and throughout the 
study. The list of events and the time when they will be performed are presented in Table 3 for 
Part A and in Table 5 for Part B (if appropriate). 
8.3.1 Laboratory Evaluation 
Local or central laboratory assessments on serum chemistry, hematology, coagulation, and 
urinalysis will be conducted, of which certain elements will be collected as specified in 
Appendix 2. Laboratory assessments need not be repeated on Day 1 if these assessments were 
completed for screening within 14 days of the first administration of the investigational 
product.   
Routine laboratory tests (eg, CBC with differential; comprehensive serum chemistry panel; 
PT/INR and aPTT; immunoglobulins; urinalysis; urine and serum β-HCG) will be performed 
by the local study site laboratory or their contract laboratory. Patient treatment and overall 
management decisions will be based on local laboratory data. Details regarding the amount of 
blood drawn for laboratory testing are provided in a laboratory reference document.   
Clinical chemistry, hematology, and urinalysis will be performed up to 14 days prior to Cycle 
1 Day 1 and at the time points specified in Table 3 and Table 5 (for Parts A and B, 
respectively), and also at mandatory Safety Follow-up Visits.  
PT/INR and aPTT should be collected at Screening and if a Grade 2 or higher hepatic AE 
occurs, as specified in Table 5.  Coagulation parameters should be evaluated more frequently 
during the study when clinically indicated. PT/INR and aPTT will be analyzed by the local 
study site laboratory. 
In the event of neutropenia (ANC < 1000/mm3), thrombocytopenia (platelets < 50,000/mm3), 
or Grade 3 clinical chemistry toxicity, the relevant assessments will be conducted as frequent 
as the physician feels needed until toxicity resolves to ≤ Grade 2. If warranted, additional 

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testing can also be done, or the relevant tests done more frequently in accordance with 
institutional guidelines. All patients, who have any Grade 3 or Grade 4 laboratory 
abnormalities at the Safety Follow-up Visits, must be followed up until they have returned to 
≤ Grade 2 or baseline, unless these are not likely to improve due to the underlying disease. 
Thyroid function which includes T3, T4, and TSH will be assessed at pre-dose of Day 1 of 
every cycle and at the mandatory Safety Follow-up Visits. If feasible, early morning 
adrenocorticotropic hormone (ACTH) and cortisol will be obtained as part of the screening 
assessments and only repeated during the study if it is clinically indicated. Analysis will be 
performed by the local study site laboratory. 
For Part B, thyroid function will be collected at screening, every 2 cycles, or more frequently 
as clinically indicated during treatment, and at the mandatory Safety Follow-up Visits.  
Analysis of IgG and IgM will be performed at pre-dose of Day 1 every cycle in first 12 months, 
approximately every 2 months thereafter, and at Safety Follow-up Visits in Part A only. 
Analysis will be performed by the local study site laboratory. 
 
 
 
 
 
 
  
A central laboratory may be used in this study.  Investigators may use results from local 
laboratories for assessing eligibility, safety monitoring and dosing decision. 
8.3.2 Physical Examination, Ophthalmologic Examinations and Vital Signs 
A complete physical examination, vital signs, and weight as well as ophthalmologic 
examination will be performed at the time points specified in Table 3 and in Table 5. In Part B, 
a full physical examination will be performed at the Screening and Safety Follow-up visits, at 
all other times targeted or symptoms-directed physical examination, at the investigators 
discretion is permitted. A full physical examination includes: examination of general 
appearance; head, eyes, ears, nose and throat; neck; heart; chest (including lungs); abdomen; 
extremities; skin; lymph nodes; cardio-vascular; and neurological status. 
ECOG performance status will be evaluated at time points specified in Table 3 and in Table 5. 
Vital signs will include body temperature, heart rate, respiratory rate, and blood pressure. To 
the extent feasible, blood pressure will be taken on the same arm throughout the study. A large 

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cuff should be used for obese patients. Patients must be resting in a sitting position for 
10 minutes prior to obtaining vital signs. If blood pressure is > 150/100 in a patient without a 
history of hypertension, or increased > 20 mmHg (diastolic) from baseline measurement in a 
patient with a previous history of hypertension, the assessment should be repeated in 
10 minutes for confirmation. 
Ophthalmologic Examination 
Eye exam, visual acuity test, and optical coherence tomography (or equivalent diagnostic test) 
will be assessed at the Screening Visit. Eye exam, visual acuity test, and optical coherence 
tomography (or equivalent diagnostic test for retinal examination) captured as standard of care 
prior to obtaining written informed consent and within 28 days of study entry may be used for 
the Screening evaluation. Patients will undergo repeat assessments approximately every 
15 weeks (± 7 days) during study treatment and a final assessment < 30 days after the last dose 
of tislelizumab study treatment.   
In addition, Investigators should solicit patients regarding changes in vision, visual 
disturbance, or ocular inflammation at each scheduled study visit during tislelizumab 
treatment. For any change in vision, referral to an appropriate specialist will be made for further 
management guidance (see Appendix 10). 
8.3.3 Medical History/ Prior Medications 
The medical history and prior medications assessments are the same for Part A and Part B. 
The medical history and current/ relevant prior medications (within the past 12 months) are 
recorded at Screening. 
History of treatment for the primary diagnosis, including prior systemic, radiation treatment, 
and surgical treatment will be recorded. Radiographic studies performed prior to study entry 
may be collected for review by the investigator. Date and response to last platinum-containing 
chemotherapy treatment must be documented unless no platinum-containing treatment has 
been received. Date of disease progression after completing platinum-containing regimen must 
be documented.  
8.3.4 Electrocardiogram 
Part A: 
Electrocardiograms will be obtained at the time points specified in Table 3 and Table 4 at 
Screening within 14 days of Cycle 1 Day 1 as baseline, and at the mandatory Safety Follow-
up Visits. Additional ECGs may be obtained if clinically indicated. 
Part B: 

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Electrocardiograms will be obtained at the time points specified in Table 5 and Table 6 at 
Screening within 14 days of Day 1 of study treatment as baseline, as clinically indicated during 
the treatment period, and at the mandatory Safety Follow-up Visits. 
For both Part A and Part B: 
Triplicate ECG recordings (3 readings in rapid succession and not more than 2 minutes apart) 
will be obtained locally at the site in conjunction with blood sampling for pamiparib 
pharmacokinetics at the times specified in Table 4 and Table 6.   ECGs required at timepoints 
that do not include a PK sample do not need to be triplicate assessments. 
Significant QTc prolongation will be defined as an interval ≥ 500 msec or an interval which 
increases by ≥ 60 msec over baseline. Either of these conditions should be documented on two 
or more ECG tracings separated by at least 5 minutes. The ECG tracing should be examined 
and a manual measurement by a trained physician should be performed to assess the accuracy 
of the equipment being used. 
If a patient has significant QTc prolongation： 
 He/she will be withdrawn from the investigational product administration if the 
investigator and/or the medical monitor determine the patient is at risk. 
 The patient will be monitored, treated appropriately, and closely followed (ECGs at least 
three times per week) until the QT and QTc interval return to within 30 msec of baseline. 
 The medical monitor will be consulted prior to administering further doses or re-
challenging with pamiparib. 
 The medical monitor will be consulted prior to administering further pamiparib. 
8.3.5 Serum Tumor Markers 
The serum tumor marker collection is to occur for Part A and Part B as per Table 3 and Table 5. 
Standard tumor markers (as appropriate for a given tumor type) will be collected at 
 
 
 
 
 
. Analysis will be performed by the local study site laboratory where 
feasible. If not feasible, tests will be performed by a certified central laboratory. 

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For both Part A and Part B: 
PSA Measurements 
Increases and decreases in PSA will be tracked to assess PSA responses by the PCWG3 criteria 
(refer to Appendix 6). PSA changes from baseline (either increment or decline) and maximal 
change in PSA will be recorded and responses assigned by PCWG3 criteria. PSA responses 
and progression must be confirmed 28 days later.  
Although serial PSA will be measured on this study and PSA progression documented by the 
PCWG3 criteria, the PSA value on its own is not considered a reliable measure of clinical 
benefit and does not correlate tightly with survival. PSA flares may occur early in the treatment 
and may therefore confound response assessment. Additionally, there is emerging data that 
PARP-1 is implicated in multiple other essential cellular functions separate from DNA repair 
including ETS gene-mediated transcription regulation which may have a bearing on the 
response assessments by PSA. PSA reading should not be applied as the sole criteria to 
consider treatment discontinuation. In absence of evidence of radiological or clinical evidence 
of disease progression, patients with mCRPC should continue in the study despite an increment 
in PSA. Overall, therefore patients will not be taken off trial purely for rising PSA levels in the 
absence of worsening scans and symptoms since PARP inhibitors may impact tumor growth 
without impacting PSA secretion. PSA response and PSA progression will be defined 
according to the consensus guidelines of the PCWG3 criteria (refer to Appendix 6). 
8.3.6 Computed Tomography 
Tumor imaging is the same for Part A and Part B as per Table 3 and Table 5. 
Tumor imaging (CT or MRI, with preference for CT) will be performed within 28 days prior 
to enrollment, and while on study approximately every 9 ± 1 weeks in the first 12 months and 
approximately every 12 ± 1 weeks thereafter and at the Safety Follow-up. Positron emission 
tomography (PET) imaging scans for treatment response evaluation are not allowed in this 
study. 
A CT scan of the thorax, abdomen, and pelvis plus other relevant evaluations as appropriate, 
including bone scan for patients with bone metastasis, will be performed to assess all known 
disease. All known disease must be documented at baseline as target or non-target lesions using 
RECIST v1.1. The CT scan will be used for the evaluation of RECIST v1.1 by the investigator 
at each study center. 
A baseline brain MRI is required for all patients in the SCLC cohort.  Patients in other cohorts 
with a known history of brain metastases must have an MRI to document the status of existing, 
previously treated brain metastases.  Brain metastases should be evaluated throughout the study 

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as part of the assessment of anti-tumor activity from the combination of tislelizumab and 
pamiparib.  
Unless contraindicated, intravenous contrast product must be used to maximize visualization 
of all lesions. Five millimeter (mm) contiguous scans at baseline and subsequent scanning 
approximately every 9 ± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks 
thereafter until progression, as calculated by the date of the first administration of the 
investigational product) until progression, with mandatory imaging coverage from thoracic 
inlet to symphysis pubis should be performed. Patients who are at increased risk of allergic 
reaction to iodinated contrast media should not have enhanced CT, but should instead be 
provided magnetic resonance imaging (MRI) with gadolinium enhancement patient to local 
protocol, with mandatory imaging coverage from thoracic inlet to symphysis pubis plus 
unenhanced CT scanning with coverage from the thoracic inlet to the inferior costophrenic 
recess. Patients with bone pain or biochemical changes suggestive of bony disease without 
other clear explanation should have a bone scan at baseline and if bone metastases are 
documented should then have bone scans or other appropriate imaging examinations as 
clinically indicated. New lesions on a bone scan should be assessed with caution and, unless 
otherwise explained, should be imaged by CT or focal radiographs.  
The same imaging technique should be used in a patient throughout the study. After first 
documentation of response (CR or PR), imaging performed at the next regularly scheduled 
time point will be used for response confirmation. PD suspected as pseudo-progression needs 
to be confirmed in a subsequent imaging at least 4 weeks later or at the next regularly scheduled 
time point before discontinuation of study treatment as described in Section 8.8.1.  
Technetium bone scans will be used to assess bone lesions. In patients with prostate cancer 
baseline bone scans will be performed during the screening window, and repeat bone scans 
will be performed approximately every 9 ± 1 weeks in the first 12 months and approximately 
every 12 ± 1 weeks thereafter until progression to keep with the schedule of the CT scans. Bone 
scan results will be reported as either no lesions or lesions present along with the number of 
bone lesions. Disease progression by bone scan will be defined per the PCWG3 (refer to 
Appendix 6); progression is defined as 2 new bone lesions at the first ‘progression’ scan, 
confirmed by a subsequent scan at least 6 weeks later with the presence of 2 additional lesions. 
Patients who stop treatment prior to documentation of PD will undergo repeated imaging for 
tumor response assessments during the study approximately every 9 ± 1 weeks in the first 
12 months and approximately every 12 ± 1 weeks thereafter until unequivocal PD is 
documented or the patient starts new anticancer therapies or patient withdraws consent from 
the trial. This imaging schedule will be maintained and will never be adjusted regardless of 
any intermediate unscheduled scans. Patients who withdraw from the study for clinical or 
symptomatic deterioration before objective documentation of PD will be requested to undergo 

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appropriate imaging to confirm PD. Every effort will be made to confirm a clinical diagnosis 
of PD by imaging. 
8.3.7 Optional Tumor Biopsy 
PART A and B:  
For those patients who consent to fresh biopsy, an optional biopsy for biomarker analysis 
during the third week of the first cycle is recommended in order to assess pharmacodynamics 
effects and resistance mechanisms (Section 8.11). For the patients who have confirmed disease 
progression, an optional biopsy may be taken at the Safety Follow-up visit only if the lesion to 
be biopsied is at low risk for complications and the patient can safely undergo the procedure.  
The purpose of this biopsy sample is to evaluate mechanisms of resistance to study treatment 
(s). If feasible, any follow up biopsy should be ideally taken from the same anatomical location 
as the baseline biopsy. Additional written patient consent is required for optional fresh tumor 
biopsies. 
8.3.8 Adverse Events 
Adverse event collection is the same for Part A and Part B as per Table 3 and Table 5. 
All AEs and SAEs, regardless of the relationship to the investigational product, will be 
collected from signing the informed consent form (ICF) and throughout the study until 30 days 
after the last study treatment or initiation of new anticancer therapy. The exception are irAEs, 
which will be recorded up to 90 days after the last dose of tislelizumab, regardless of initiation 
of subsequent anticancer therapy. 
8.4 
Safety Assessments 
Overall safety assessment is the same for Part A and Part B as per Table 3 and Table 5. 
Vital signs, weight, physical examinations, ophthalmologic examinations, ECOG performance 
status, ECGs and laboratory safety tests (eg, PT/aPTT, urinalysis, CBC, serum chemistries, 
autoantibodies, thyroid function, viral antigen reactions) will be obtained and assessed at 
designated intervals throughout the study (see Table 3 and Table 5). Special attention will be 
given to irAEs (eg, gut, skin, lung, liver, kidney, endocrine organs, others). If irAE of the liver 
occurs, a biopsy of the liver is strongly encouraged. 
Adverse events will be graded and recorded throughout the study according to NCI-CTCAE, 
version 4.03. [86] Characterization of toxicities will include severity, duration, and time to 
onset. Safety endpoints will include all types of AEs, in addition to laboratory safety 
assessments, ECOG performance scale status, ECGs, and vital signs. 

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8.4.1 Safety Evaluation 
The continuous safety evaluation will be performed by the sponsor, the coordinating 
investigator, and investigators. In Part A, a SMC is established for the determination of DLs 
to be administered during dose escalation phase and dose regimens in this study. Details of the 
safety monitoring process will be specified in a dedicated study management plan. 
The SMC consists of the coordinating investigator, selected recruiting investigators, the 
sponsor’s medical monitor, and the contract research organization’s (CRO) medical monitor. 
Ad hoc members will be consulted as needed and may include, but are not restricted to the 
biostatistician and pharmacokinetic scientist. 
The SMC will decide on DLTs relevant for the treatment and will decide by consensus on dose 
escalation, dose de-escalation, or suspension of enrollment based on safety and/or on PK data.  
Before moving to the next dose level, the SMC will review all safety data available to 
determine whether recruitment to the next cohort should be initiated. The SMC will determine 
when no further dose escalation is appropriate and whether the MTD will be defined as a 
preceding dose or an intermediate dose. 
The SMC will meet for cohort safety reviews after all patients in a dosing cohort have 
completed the first treatment cycle. All available safety data will also be provided for patients 
who discontinue prior to this time. Safety data from prior cohorts may also be presented. The 
decision to escalate dose and the determination of the MTD will be based on the cohort safety 
reviews. The SMC will review any protocol violations that may have impacted evaluation of 
potential DLT. The SMC may weigh collective evidence and may determine a DLT for reasons 
in addition to those explicitly stated in the final protocol. 
Response from all SMC members, or their designees, shall be required for each 
escalation/review. 
Adequate time for review of results will be given to SMC members (approximately 1 to 
2 business days). Enrollment in subsequent DLs will be put “on hold” during each review 
period, pending the decision of the SMC. 
The SMC decision points may fall into one of the categories detailed below: 
 Escalate to a higher dose 
 Recruit additional patients into existing dose level or expansion cohort 
 Explore any other DLs; ie, an intermediate, not pre-defined, previously evaluated or 
not previously evaluated dose level below MTD 
 Stop escalation and investigate lower dose(s) 

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 End part of the study 
 End the overall study 
Decisions will be made using the criteria defined within the protocol (see Section 5.1.1). The 
SMC will make the dose escalation decisions. 
The SMC may decide to evaluate an intermediate, not pre-defined, previously evaluated or not 
previously-evaluated dose or a less frequent dosing schedule that will not exceed the MTD 
level, if evaluation of toxicity at such a dose or schedule is desired. If this approach is taken, 
up to 6 new patients should be enrolled at that dose or schedule. 
In Part B of the study, the sponsor and its designees will review the safety (eg, related 
procedure adverse events and serious adverse events; disease related events do not need to be 
reported) on a routine basis and will discuss any significant safety findings with the 
investigators immediately. If necessary, an SMC including investigators treating patients in 
each disease-specific cohort may be convened for review of safety data and/or assessment of 
benefit/risk. 
8.5 
Follow-up Assessments 
Generally, the overall follow-up strategy is the same for Part A and Part B as per Table 3 and 
Table 5. 
All patients must be followed for at least 30 days after their last dose of study drug or until 
initiation of a new anticancer treatment, whichever occurs first. 
Patients who are discontinued from the study due to an unacceptable drug-related AE will be 
followed until the resolution of the AE to ≤ Grade 1 or stabilization or non-laboratory toxicities 
to allow for re-treatment agreed by investigators and medical monitor or until beginning of a 
new therapy for their cancer, whichever occurs first.  
In Part A, a mandatory Safety Follow-up Visit should be conducted 30 days (± 7 days) after 
the last dose of study drug administration or initiation of new anticancer therapy, whichever 
occurs first. Following completion or discontinuation of the treatment and/or Safety Follow-
up phases of the study, every effort should be made to follow up all patients for their survival 
status until patient death. 
In Part B, a mandatory Safety Follow-up Visit should be conducted 30 days (± 7 days) after 
the last dose of pamiparib administration and 90 days (± 14 days) after the last dose of 
tislelizumab or initiation of new anticancer therapy, whichever occurs first. With the exception 
of all irAEs, which will be recorded up to 90 days after the last dose of tislelizumab, regardless 
of initiation of subsequent anticancer therapy. Patients who have not demonstrated disease 
progression will have contrast CT of chest, abdomen (or MRI for patients who are allergic to 

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contrast) and pelvis conducted approximately every 9 ± 1 weeks in the first 12 months and 
approximately every 12 ± 1 weeks thereafter until unequivocal PD is documented or the patient 
starts new anticancer therapies or patient withdraws consent from the trial. The same 
methodology should be used throughout the study.  
Patients who stop treatment prior to documentation of PD will undergo repeated imaging for 
tumor response assessments during the study approximately every 9 ± 1 weeks in the first 
12 months and approximately every 12 ± 1 weeks thereafter until unequivocal PD is 
documented or the patient starts new anticancer therapies or patient withdraws consent from 
the trial. This imaging schedule will be maintained and will never be adjusted regardless of 
any intermediate unscheduled scans. Patients who withdraw from the study for clinical or 
symptomatic deterioration before objective documentation of PD will be requested to undergo 
appropriate imaging to confirm PD. Every effort will be made to confirm a clinical diagnosis 
of PD by imaging. 
Following completion of the treatment and safety follow-up periods, all patients will be 
followed for survival and subsequent anticancer therapy information after the treatment 
termination. Survival follow-up and subsequent anticancer therapy information will be 
collected during telephone calls, through patients’ medical records, and/or at clinic visit every 
3 months until death, loss to follow-up or study termination by the sponsor. No other data (eg, 
subsequent therapies, performance status, etc.) beyond survival will be collected during these 
calls/visits. The study staff may use a public information source (eg, county records) to obtain 
information about survival status only. 
8.6 
Visit Windows 
All visits must occur within the windows specified in Table 3 and Table 5.  All assessments 
will be performed on the day of the specified visit unless an acceptable visit window is 
specified.  Assessments scheduled on the day of study treatment administration (Day 1) of each 
cycle should be performed prior to study treatment infusion/dose unless otherwise noted.  
Laboratory results are required to be reviewed prior to dosing. 
If the timing of a protocol-mandated study visit coincides with a holiday, weekend, or other 
events, the visit should be scheduled on the nearest feasible date (the visit window is provided 
in Table 3 and Table 5), with subsequent dosing continued on the 21-day intervals accordingly, 
with a minimum of 14 days between tislelizumab dosing. 
8.7 
Unscheduled Visits 
Unscheduled visits may be performed at any time at the patient’s or investigator’s request and 
may include vital signs/focused physical examination; ECOG performance status; AE review; 
concomitant medications and procedures review; radiographic assessments; physical 

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examination of liver, spleen, and lymph nodes; disease-related constitutional symptoms; and 
hematology and chemistry laboratory assessments.  The date and reason for the unscheduled 
visit must be recorded in the source documentation.   
If an unscheduled visit is necessary to assess toxicity or for suspected disease progression, then 
diagnostic tests may be performed based on investigator assessment as appropriate, and the 
results of these tests should be entered on the unscheduled visit eCRF. 
8.8 
Efficacy Assessment 
This study includes preliminary assessments of efficacy (anti-tumor activity) as outlined in the 
sections below for both Part A and Part B. 
Disease assessment by radiographic imaging (CT or MRI, with a preference for CT) will be 
performed and recorded at screening within 28 days before enrollment and while on study 
approximately every 9± 1 weeks in the first 12 months and approximately every 12 ± 1 weeks 
thereafter according to the RECIST v1.1 Guidelines as shown in Appendix 8. The same 
imaging technique as used at baseline must be used throughout the study. If any study patient 
discontinues study treatment for clinical progression, every attempt should be made to confirm 
PD using standard radiologic methods. 
After first documentation of CR or PR, imaging performed at the next regularly scheduled time 
point will be used for response confirmation. 
For patients with ovarian, fallopian tube, or primary peritoneal cancer, investigators may also 
incorporate GCIG CA-125 response criteria with RECIST Version 1.1 response criteria in 
assessing tumor response (refer to Appendix 4).  
For patients with prostate cancer, PCWG3 criteria will also be used to evaluate PSA and 
modified RECIST responses.  
8.8.1 Disease Progression and Treatment beyond Disease Progression 
There is evidence that some patients treated with anti-PD-1 therapies such as tislelizumab may 
derive clinical benefit despite initial documentation of PD by RECIST Version 1.1. Pseudo-
progression may occur due to immune cell infiltration and other mechanisms as manifested by 
apparent increase of existing tumor masses or appearance of new tumor lesions. [87] For PD 
suspected by the Investigator as pseudo-progression, treatment may continue until 
confirmation of PD with repeat imaging at least 4 weeks later or at the next regularly scheduled 
imaging time point, but not more than 12 weeks from the initial documentation of pseudo-
progression.  The criteria for pseudo-progression will not be satisfied if the only disease-
specific finding is a change in tumor markers (eg, CA-125, PSA increases). It is the 
responsibility of the Investigator to determine if the patient should be considered for treatment 

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beyond progression due to clinical benefit. This decision should be considered carefully so as 
to permit patients who are likely to be benefiting to continue treatment while at the same time 
preventing prolonged exposure of a futile therapy in patients who may not be benefiting. The 
assessment of clinical benefit should take into account whether the patient is clinically 
deteriorating and unlikely to receive further benefit from continued treatment. All decisions to 
continue treatment beyond initial progression must be documented in the medical record, and 
agreed to by the sponsor medical monitor.   
Patients will be permitted to continue study treatment beyond initial RECIST v1.1 defined PD 
for the time periods below and if they meet the following criteria: 
 Investigator-assessed clinical benefit  
 Patient is tolerating study drug and agrees to continued study treatment. 
 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 
 Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (eg, cord compression) that necessitates urgent alternative medical intervention 
 Patient agrees to continued treatment and is re-consented to continue study treatment 
For mCRPC patients with only bone lesion(s), if there is ambiguity about the appearance of 
the bony lesions such as traumatic in nature or concern about the possibility of healing bone 
having the appearance of sclerosis (flare reaction), and the investigators assess that those 
patients could receive further clinical benefit from the treatment and should also meet the 
criteria listed above for treatment beyond PD defined by initial RECIST v1.1. Those patients 
will be permitted to continue study treatment beyond second confirmed PD by bone scan. 
These cases should be discussed with the sponsor or its designee.  
8.9 
Pharmacokinetics 
Blood will be collected to characterize the PK of tislelizumab and pamiparib. In Part A of the 
study, PK parameters such as Cmax, Ctrough and Tmax for pamiparib may be derived for each 
cycle at which pharmacokinetics are to be measured; Ctrough may be derived for tislelizumab. 
In Part B of the study, PK parameters such as Ctrough may be derived for both pamiparib and 
tislelizumab for each cycle at which pharmacokinetics are to be measured. Additional PK 
analyses will be conducted as appropriate in all patients for whom valid tislelizumab and 
pamiparib PK parameters can be estimated. 
Blood taken for the PK analysis will be collected at the time points presented in Table 4 and 
Table 6. In addition, tislelizumab PK samples at pre-dose will be collected at the same time 
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Details concerning handling of the PK serum and plasma samples, including labeling and 
shipping instructions will be provided in the Laboratory Manual. The actual time each sample 
was collected will be captured to the nearest minute in the eCRF and recorded in the database. 
Samples will be shipped to the central laboratory where all samples will be analyzed for serum 
tislelizumab and plasma pamiparib concentrations using a validated method. 
8.9.1 Blood Sample Collection and Handling 
Cannulation for blood sampling for PK will be performed. PK samples should not be drawn 
from the infusion line or from the same arm of infusion. Blood will be collected via the 
intravenous cannula pre-dose and at the time points specified in Table 4 and Table 6. The actual 
time each sample was collected will be captured to the nearest minute in the eCRF. 
Blood samples for PK analysis will be collected according to the Laboratory Manual. Plasma 
(for pamiparib) and serum (for tislelizumab) will be separated and immediately frozen. 
Samples must remain frozen. Temperatures and tissue handling during shipment are specified 
in the Laboratory Manual. 
Samples will be shipped to a central laboratory where they will be analyzed for serum 
tislelizumab and plasma pamiparib concentrations using a validated method. 
Other Blood Samples  
Blood samples should be obtained, when possible, for analysis of serum tislelizumab and 
plasma pamiparib per time-point, in the event of a DLT. The investigator must record the time 
points the blood samples obtained and the time of the previous administration in the eCRF. 
Should a DDI between tislelizumab and/or pamiparib, and a concomitant medication be 
suspected, further blood samples for PK analyses may be taken to characterize the extent of 
the potential interaction. 
8.10 Anti-Drug Antibody 
Immunogenic responses to tislelizumab will be assessed to determine occurrence of anti-
tislelizumab antibody. For Part A, as specified in Table 4, blood for anti-tislelizumab 
antibodies should be collected within 24 hours before the start of infusion on Day 1 and one 
sample between Day 7 through 10 of Cycle 1, and before the start of infusion on Day 1 of 
Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 9 in the first 6 months, approximately every 8 cycles 
thereafter (Cycle 17). For Part B, as specified in Table 6, blood for anti-tislelizumab antibodies 
should be collected within 24 hours before the start of infusion on Day 1 and one sample 
between Day 7 through 10 of Cycle 1, and before the start of infusion on Day 1 of Cycle 2, 

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Cycle 3, Cycle 4, Cycle 5, Cycle 9 in the first 6 months, approximately every 8 cycles thereafter 
(Cycle 17).  
In patients who discontinue study therapy before 6 months, every effort should be made to 
analyze anti-tislelizumab antibodies approximately 6 months after the first dose. tislelizumab 
PK samples at pre-dose will be collected at the same time points as the ADA samples to assess 
the neutralizing capacity of ADA. Samples will be processed according to the Laboratory 
Manual and shipped to a central laboratory for analysis using a validated method. 
8.11 Biomarker Assessments 
A blood sample at screening stage will be collected for ovarian, fallopian tube, primary 
peritoneal, and breast cancer patients enrolled in Part A and in all patients in Part B for 
germline BRCA and/or other mutations analysis, even if it has been tested previously. Blood 
samples will be prepared as indicated in the Laboratory Manual.  

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8.12 Appropriateness of Measurements 
All safety and PK assessments used in this study are standard, ie, widely used and generally 
recognized as reliable, accurate, and relevant.  

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9.0 QUALITY CONTROL AND QUALITY ASSURANCE 
According to the Good Clinical Practice (GCP) guidelines [88], the sponsor is responsible for 
implementing and maintaining quality assurance and quality control systems with written 
Standard Operating Procedures (SOPs). 
Quality control will be applied to each stage of data handling. 
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data: 
 
Investigator meeting(s) 
 
Certified local laboratories for laboratory measurements and ECGs 
 
Study center initiation visit 
 
Early study center visits post-enrollment 
 
Routine study center monitoring 
 
Ongoing study center communication and training 
 
Data management quality control checks 
 
Continuous data acquisition and cleaning 
 
Internal review of data 
 
Quality control check of the final clinical study report 
In addition, the sponsor and/or the CRO’s clinical quality assurance department may conduct 
periodic audits of the study processes, including, but not limited to the study center, study 
center visits, PK laboratories, local laboratories, vendors, clinical database, and the final 
clinical study reports. When audits are conducted, access must be authorized for all 
study-related 
documents 
including 
medical 
history 
and 
concomitant 
medication 
documentation to authorized sponsor’s representatives and regulatory authorities. 
9.1 
Monitoring 
In accordance with applicable regulations, GCP, and sponsor procedures, the sponsor has 
engaged the services of a CRO to perform all monitoring functions within this clinical study. 
Monitors will work in accordance with the sponsor or CRO SOPs and have the same rights 
and responsibilities as monitors from the sponsor’s organization. Monitors will establish and 
maintain regular contact between the investigator and the sponsor. 
During these contacts, the monitor will: 
 Check the progress of the study. 

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 Review study data collected. 
 Conduct source document verification. 
 Identify any issues and address their resolution. 
This will be done to verify that the: 
 Data are authentic, accurate, and complete. 
 Safety and rights of patients are being protected. 
 Study is conducted in accordance with the currently approved protocol (and any 
amendments), GCP, and all applicable regulatory requirements. 
The investigator agrees to allow the monitor direct access to all relevant documents and to 
allocate his/her time and the time of his/her personnel to the monitor to discuss findings and 
any relevant issues. 
At study closure, monitors will also conduct all activities described in Section 13.1. 
9.2 
Data Management/Coding 
Data generated within this clinical study will be handled according to the relevant SOPs of the 
data management and biostatistics departments of the sponsor or the delegated CRO. 
An electronic data capture (EDC) system will be used for this study, meaning that all eCRF 
data will be entered in electronic forms at the study center. Data collection will be completed 
by authorized study center personnel designated by the investigator. Appropriate training and 
security measures will be completed with the investigator and all authorized study center 
personnel prior to the study being initiated and any data being entered into the system for any 
patients. 
The eCRFs should always reflect the latest observations on the patients participating in the 
study. Therefore, the eCRFs are to be completed ASAP during or after the patient’s visit. To 
avoid inter-observer variability, every effort should be made to ensure that the same individual 
who made the initial baseline determinations completes all safety evaluations. The investigator 
must verify that all data entries in the eCRFs are accurate and correct. If some assessments are 
not done, or if certain information is not available or not applicable or unknown, the 
investigator should indicate this in the eCRF. The investigator will be required to electronically 
sign off on the clinical data. 
The monitor will review the eCRFs and evaluate them for completeness and consistency. The 
eCRF will be compared with the source documents to ensure that there are no discrepancies 
between critical data. All entries, corrections, and alterations are to be made by the responsible 

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investigator or his/her designee. The monitor cannot enter data in the eCRFs. Once clinical 
data of the eCRF have been submitted to the central server, corrections to the data fields will 
be audit trailed, meaning that the reason for change, the name of the person who performed the 
change, together with time and date will be logged. Roles and rights of the study center 
personnel responsible for entering the clinical data into the eCRF will be determined in 
advance. If additional corrections are needed, the responsible monitor or data manager will 
raise a query in the EDC application. The appropriate study center personnel will answer 
queries sent to the investigator. 
The eCRF is essentially considered a data entry form and should not constitute the original (or 
source) medical records unless otherwise specified. Source documents are all documents used 
by the investigator or hospital that relate to the patient’s medical history, that verify the 
existence of the patient, the inclusion and exclusion criteria and all records covering the 
patient’s participation in the study. They include laboratory notes, ECG results, memoranda, 
pharmacy dispensing records, patient files, etc. 
The investigator is responsible for maintaining source documents. These will be made 
available for inspection by the study monitor at each monitoring visit. The investigator must 
submit a completed eCRF for each patient who receives the investigational product, regardless 
of the duration. All supportive documentation submitted with the eCRF, such as laboratory or 
hospital records, should be clearly identified with the study and patient number. Any personal 
information, including patient name, should be removed or rendered illegible to preserve 
individual confidentiality. 
Electronic CRF records will be automatically appended with the identification of the creator, 
by means of their unique UserID. Specified records will be electronically signed by the 
investigator to document his/her review of the data and acknowledgement that the data are 
accurate. This will be facilitated by means of the investigator’s unique UserID and password; 
date and time stamps will be added automatically at the time of the electronic signature. If an 
entry on an eCRF requires change, the correction should be made in accordance with the 
relevant software procedures. All changes will be fully recorded in a protected audit trail, and 
a reason for the change will be required. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) Version 17.0 or higher versions. Concomitant medications will be coded using the 
World Health Organization Drug Dictionary Enhanced (WHO-DD). Concomitant 
diseases/medical history will be coded using the MedDRA Version 17.0 or higher versions. 
9.3 
Quality Assurance Audit 
To ensure compliance with GCP and all applicable regulatory requirements, the sponsor may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 

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inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution agree 
to allow the auditor/inspector direct access to all relevant documents and to allocate his/her 
time and the time of his/her personnel to the auditor/inspector to discuss findings and any 
relevant issues. 
 

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10.0 SAFETY MONITORING AND REPORTING 
The investigator is responsible for the monitoring and documentation of events that meet the 
criteria and definition of an AE or SAE as provided in this protocol. 
10.1 Risks Associated with Tislelizumab 
Tislelizumab is an investigational agent that is currently in clinical development. Limited 
safety data are available in patients and the full safety profile has not been characterized. The 
following information is based on results from nonclinical and clinical studies with 
tislelizumab and published data on other molecules within the same biologic class. 
The PD-L1/PD-1 pathway is involved in peripheral tolerance; therefore, such therapy may 
increase the risk of irAEs, specifically the induction or enhancement of autoimmune 
conditions. Immune-related AEs commonly associated with anti-PD-1 therapy are presented 
in Table 9.   
Although most irAEs observed with immunomodulatory agents have been mild and 
self-limiting, such events should be recognized early and treated promptly to avoid potential 
major complications. Guidance for evaluation and management for suspected irAEs are 
provided in Section 10.13.4 and Appendix 10. 
10.2 General Plan to Manage Safety Concerns 
10.2.1 Eligibility Criteria 
Eligibility criteria were selected to guard the safety of patients in this trial. Results from the 
nonclinical toxicology studies and clinical data with tislelizumab and pamiparib, as well as the 
nonclinical/clinical data from other PD-L1/PD-1/PARP inhibitors, were taken into account. 
Specifically, patients at risk for study-emergent active autoimmune diseases or history of 
autoimmune diseases that may relapse, and patients who have received a live viral vaccine 
within 28 days before study entry are excluded from the study.  
10.2.2 Safety Monitoring Plan 
Safety will be evaluated in this study through the monitoring of all serious and non-serious 
adverse events, defined and graded according to NCI-CTCAE v4.03. Patients will be assessed 
for safety (including laboratory values) according to the schedule in Table 3 and Table 5. 
Clinical laboratory results must be reviewed prior to the start of each cycle. 
In this study, all enrolled patients will be evaluated clinically and with standard laboratory tests 
before and at regular intervals during their participation in this study. Safety evaluations will 
consist of medical interviews, recording of AEs, physical examinations, laboratory 
measurements (eg, hematology, chemistry) and other assessments. In addition, patients will be 

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closely monitored for the development of any signs or symptoms of autoimmune conditions 
and infection. 
Serum samples will be drawn from patients for the determination of ADAs to tislelizumab. 
Administration of tislelizumab will be performed in a setting where emergency medical 
equipment and staff who are trained to respond to medical emergencies are available.  
All AEs will be recorded during the trial (AEs from the time of the first dose and SAEs from 
the time of signing of informed consent) and for up to 30 days after last dose of pamiparib and 
up to 90 days after tislelizumab study treatment or initiation of new anticancer therapy, 
whichever occurs first. At the end of treatment, ongoing AEs considered related to study 
treatment will be followed until the event has resolved to baseline or ≤ Grade 1, the event is 
assessed by the Investigator as stable, the patient is lost to follow-up, the patient withdraws 
consent. 
All irAEs will be recorded up to 90 days after the last dose of tislelizumab, regardless of 
initiation of subsequent anticancer therapy. All drug-related SAEs will be recorded by the 
Investigator after treatment discontinuation until patient death or loss to follow-up, whichever 
occurs first. 
Investigators are instructed to report all events (including AEs and pregnancy-related AEs). 
The potential safety issues anticipated in this trial, as well as measures intended to avoid or 
minimize such toxicities, are outlined in the following sections. 
10.3 Adverse Events 
10.3.1 Definition and Reporting of an Adverse Event 
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 
study drug, whether considered related to study drug or not.  
Examples of an AE include:  
 Worsening of a chronic or intermittent pre-existing condition including an increase in 
severity, frequency, duration, and/or has an association with a significantly worse 
outcome  
 New conditions detected or diagnosed after study drug administration even though it 
may have been present before the start of the study  
 Signs, symptoms, or the clinical sequelae of a suspected interaction  
 Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug 
or a concurrent medication (overdose per se should not be reported as an AE or SAE)  

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When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory results and diagnostics reports) relative 
to the AE or SAE. The investigator will then record all relevant information regarding an AE 
or SAE in the eCRF. However, there may be instances when copies of medical records for 
certain cases are requested by the sponsor. In this instance, all patient identifiers will be blinded 
on the copies of the medical records prior to submission to the sponsor.  
For the purposes of this study, all events of MDS and AML that occur while on study should 
be reported as an SAE because these events are clinically significant (see Section 0). 
10.3.1.1 Assessment of Severity 
The investigator will make an assessment of severity for each AE and SAE reported during the 
study. AEs and SAEs should be assessed and graded based upon the National Cancer Institute 
(NCI) CTCAE v4.03. 
Toxicities that are not specified in the NCI-CTCAE will be defined as follows: 
 Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated  
 Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)  
 Grade 3: severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL  
 Grade 4: life-threatening consequences; urgent intervention indicated  
 Grade 5: death related to AE  
NOTE: The terms “severe” and “serious” are not synonymous. Severity is a measure of 
intensity (for example, grade of a specific AE, mild [Grade 1], moderate [Grade 2], severe 
[Grade 3], or life-threatening [Grade 4]), whereas seriousness is classified by the criteria based 
on the regulatory definitions. Seriousness serves as the guide for defining regulatory reporting 
obligations from the sponsor to applicable regulatory authorities as described in Section 10.4. 
10.3.1.2 Assessment of Causality 
The investigator is obligated to assess the relationship between the study drug and the 
occurrence of each AE or SAE. The investigator will use clinical judgment to determine the 
relationship. Alternative causes, such as natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the AE or SAE to the study drug 
will be considered and investigated. The investigator will also consult the IB and/or Product 
Information, for marketed products, in the determination of his/her assessment. 

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There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that 
the investigator always makes assessment of causality for every SAE prior to transmission of 
the SAE report/eCRF to the sponsor since the causality assessment is one of the criteria used 
when determining regulatory reporting requirements. The investigator may change his/her 
opinion of causality in light of follow-up information, amending the SAE report/eCRF 
accordingly.  
The causality of each AE should be assessed and classified by the Investigator as “related” or 
“not related”. An AE is considered related if there is “a reasonable possibility” that the AE 
may have been caused by the study drug (ie, there are facts, evidence, or arguments to suggest 
possible causation). A number of factors should be considered in making this assessment, 
including: 
 Temporal relationship of the AE to the administration of study treatment/study 
procedure 
 Whether an alternative etiology has been identified  
 Mechanism of action of the study drug 
 Biological plausibility 
An AE should be considered ‘related’ to study drug if any of the following are met: 
 There is clear evidence to suggest a causal relationship, and other possible contributing 
factors can be ruled out. 
 There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely. 
 There is some evidence to suggest a causal relationship (eg, the AE occurred within a 
reasonable time after administration of the study drug). However, the influence of other 
factors may have contributed to the AE (eg, the patient’s clinical condition or other 
concomitant AEs). 
10.3.1.3 Follow-Up of Adverse Events 
After the initial AE or SAE report, the investigator is required to proactively follow each 
patient and provide further information to the sponsor on the patient’s condition. 
All AEs and SAEs documented at a previous visit/contact and designated as ongoing will be 
reviewed at subsequent visits/contacts. 
All AEs and SAEs will be followed until resolution, the condition stabilizes or is considered 
chronic, the AE or SAE is otherwise explained, the patient is lost to follow-up, the patient 
withdraws consent, or starts a new anticancer therapy. Once resolved, the appropriate AE or 
SAE eCRF page(s) will be updated. The investigator will ensure that follow-up includes any 
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AE or SAE. This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
The sponsor may request that the investigator perform or arrange for the conduct of 
supplemental measurements and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obligated to assist. If a patient dies 
during participation in the study or during a recognized follow-up period, the sponsor will be 
provided with a copy of any post-mortem findings, including histopathology. 
New or updated information will be recorded on the originally completed SAE report/eCRF, 
with all changes signed and dated by the investigator. The updated SAE report/eCRF should 
be resent to the sponsor within the time frames outlined in Section 10.8.1. 
10.3.1.4 Laboratory Test Abnormalities 
Abnormal laboratory findings (eg, clinical chemistry, CBC, coagulation, or urinalysis) or other 
abnormal assessments (eg, ECGs, X-rays, or vital signs) that are judged by the investigator as 
clinically significant will be recorded as AEs or SAEs if they meet the definition of an AE (as 
defined in Section 10.3.1) or an SAE (as defined in Section 10.4). Clinically significant 
abnormal laboratory findings or other abnormal assessments that are detected during the study 
or are present at baseline and significantly worsen following the start of the study will be 
reported as AEs or SAEs. However, clinically significant abnormal laboratory findings or other 
abnormal assessments that are associated with the disease being studied, unless judged by the 
investigator as more severe than expected for the patient’s condition, or that are present or 
detected at the start of the study and do not worsen, will not be reported as AEs or SAEs. They 
should be reported as AEs or SAEs if they induce clinical signs or symptoms, need active 
intervention, need dose interruption or discontinuation or are clinically significant in the 
opinion of the investigator. 
Abnormalities in liver function tests (ALT, AST, total bilirubin) that are Grade 3 or 
higher need to be reported to the sponsor with 24 hours of occurrence. Repeat LFT 
testing should be performed according to the schedule in Appendix 10. 
The investigator will exercise his/her medical and scientific judgment in deciding whether 
other abnormal laboratory finding or other abnormal assessment is clinically significant. 
10.4 Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence that, at any dose:  
 Results in death  
 Is life-threatening  
NOTE: The term “life-threatening” in the definition of “serious” refers to an AE in 
which the patient was at risk of death at the time of the AE. It does not refer to an AE, 
which hypothetically might have caused death, if it were more severe.  

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 Requires hospitalization or prolongation of existing hospitalization  
NOTE: In general, hospitalization signifies that the patient was admitted (usually 
involving at least an overnight stay) to the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the AE is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.  
 Results in disability/incapacity  
NOTE: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences of 
relatively minor medical significance, such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (eg, sprained ankle), which may 
interfere or prevent everyday life functions, but do not constitute a substantial 
disruption.  
 Is a congenital anomaly/birth defect  
 Is considered a significant medical AE by the investigator based on medical judgement 
(eg, may jeopardize the patient or may require medical/surgical intervention to prevent 
one of the outcomes listed above)  
The following are NOT considered SAEs: 
 Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline 
 Hospitalization for social/convenience considerations 
 Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience 
10.5 
Timing, Frequency, and Method of Capturing Adverse Events 
and Serious Adverse Events 
10.5.1 Adverse Event Reporting Period 
During the pre-screening stage, no adverse events will be reported. Only serious adverse events 
will be reported during the pre-screening stage if the serious adverse event is related to the 
pre-screening procedure. 
After informed consent has been signed but prior to the administration of the study drug, only 
SAEs should be reported. 

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After initiation of study drug, all AEs and SAEs, regardless of relationship to study drug, will 
be reported until 30 days after the last study treatment or initiation of new anticancer therapy. 
After this period, the investigator should report any SAEs that are believed to be related to 
prior study drug treatment. Immune-related adverse events should be reported if they occur 
within 90 days after the last dose of tislelizumab, regardless of initiation of subsequent 
anticancer therapy. 
10.5.2 Eliciting Adverse Events 
The investigator or designee will ask about AEs by asking the following standard questions: 
 How are you feeling?  
 Have you had any medical problems since your last visit?  
 Have you taken any new medicines since your last visit?  
10.6 
Specific Instructions for Recording Adverse Events and Serious 
Adverse Events 
10.6.1 Disease Progression 
Disease progression (including fatal disease progression), which is expected in this study 
population and measured as an efficacy endpoint, should not be reported as an AE term.  
Instead, the symptoms, signs or clinical sequelae that result from disease progression should 
be reported as the AE term(s).   
For instance, a patient presents with pleural effusion resulting from disease progression of 
metastasis to lungs. The event term should be reported as “pleural effusion” instead of disease 
progression. If a patient experienced a fatal multi-organ failure due to disease progression, the 
term “multi-organ failure” should be reported as the SAE with death as outcome instead of 
reporting “fatal disease progression” or “death due to disease progression”. 
10.6.2 Death 
Death is an outcome and not usually considered an event. If the only information available is 
death and the cause of death is unknown, then the death is reported as an event, eg, “death”, 
“death of unknow cause”, or “death unexplained”. 
10.7 Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is a serious adverse reaction that is 
both unexpected (ie, not present in the product’s Reference Safety Information [RSI]) and 
meets the definition of a serious adverse drug reaction (SADR), the specificity or severity of 
which is not consistent with those noted in the Investigator’s Brochure.  

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10.8 Prompt Reporting of Serious Adverse Events 
10.8.1 Timeframes for Submitting Serious Adverse Events 
As soon as the investigator determines that an AE meets the protocol definition of an SAE, the 
event must be reported promptly to the sponsor or designee as described in Table 7. 
Table 7: Time Frame for Reporting Serious Adverse Events to the Sponsor or Designee 
 
Timeframe for 
Making Initial 
Report 
Documentation 
Method 
Timeframe for 
Making Follow-
up Report 
Documentation 
Method 
Reporting 
Method 
All SAEs  
Within 24 hours of 
first knowledge of 
the SAE 
SAE Report 
As expeditiously 
as possible 
SAE Report 
Email or fax 
SAE form or 
Pregnancy 
form 
   Abbreviations: AE, adverse event; SAE, serious adverse event. 
 
Abnormalities in liver function tests (ALT, AST, total bilirubin) that are Grade 3 or higher 
need to be reported to the sponsor with 24 hours of occurrence. Repeat LFT testing should be 
performed according to the schedule in Appendix 10. 
10.8.2 Completion and Transmission of the Serious Adverse Event Report 
Once an investigator becomes aware that an SAE has occurred in a patient, he/she will report 
the information to the sponsor within 24 hours as outlined in Section 10.8.1. The SAE Report 
will always be completed as thoroughly as possible with all available details of the SAE, and 
forwarded to the sponsor or designee within the designated time frames.  
If the investigator does not have all information regarding an SAE, he/she will not wait to 
receive additional information before notifying the sponsor or designee of the SAE and 
completing the form. The form will be updated when additional information is received. 
The investigator will always provide an assessment of causality at the time of the initial report 
as described in Section 10.3.1.2. 
The sponsor will provide contact information for SAE receipt. 
10.8.3 Regulatory Reporting Requirements for Serious Adverse Events 
The investigator will promptly report all SAEs to the sponsor in accordance with the 
procedures detailed in Section 10.8.2. The sponsor has a legal responsibility to notify, as 
appropriate, both the local regulatory authority and other regulatory agencies about the safety 
of a product under clinical investigation.  
The investigator, or responsible person according to local requirements, will comply with the 
applicable local regulatory requirements related to the reporting of SAEs to regulatory 
authorities and the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 

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This protocol is being conducted under an Investigational New Drug (IND) with the US FDA.  
All IND safety reports submitted to the FDA will also be sent to all investigators conducting 
studies under this IND. 
When a study center receives an initial or follow-up safety report or other safety information 
(eg, revised Investigator’s Brochure) from the sponsor, the investigator or designated 
responsible person is required to promptly notify his/her IRB or IEC. 
10.9 Pregnancy Reporting 
If a female patient or the partner of a male patient becomes pregnant while receiving 
investigational therapy or within 6 months after the completion of the last dose of study drug, 
a pregnancy report form should be completed and expeditiously submitted to the sponsor to 
facilitate outcome follow-up. Information on the status of the mother and child will be 
forwarded to the sponsor. Generally, follow-up will be no longer than 6 to 8 weeks following 
the estimated delivery date. Any premature termination of the pregnancy will be reported. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be recorded as an AE or SAE. 
An abortion, whether accidental, therapeutic, or spontaneous should be always reported as an 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a patient exposed to the 
study drug should be recorded and reported as an SAE.  
10.10 Post-study Adverse Event 
A post-study AE or SAE is defined as any AE that occurs outside of the AE/SAE reporting 
period, defined in Section 10.5.1. 
Investigators are not obligated to actively seek AEs or SAEs in former patients. However, if 
the investigator learns of any SAE, including a death, at any time after a patient has been 
discharged from the study, and he/she considers the SAE related to the study drug, the 
investigator will notify the sponsor. 
10.11 Assessing and Recording Immune-Related Adverse Events 
Since treatment with anti-PD-1 therapy can cause autoimmune disorders, AEs considered by 
the investigator to be immune-related (see Section 10.13.4) should be classified as irAEs and 
identified as such in the eCRF AE page until up to 90 days after the last dose of tislelizumab, 
regardless of initiation of subsequent anticancer therapy. 
Investigators should consult the guidance on diagnostic evaluation and management of irAEs, 
which are commonly seen with immune checkpoint inhibitors, in Appendix 10. 

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An extensive list of potential irAEs appears in Section 10.13.4, Table 8.  All conditions similar 
to those listed should be evaluated to determine whether they are irAEs, based on a similar 
diagnostic process to those reactions that are presented in more detail in Appendix 10. 
10.12 Expedited Reporting to Health Authorities, Ethics Committees and 
Investigators 
The sponsor will promptly assess all SAEs against cumulative study drug experience to 
identify and expeditiously communicate new safety findings to regulatory authorities, 
investigators, IRBs and IECs based on applicable legislation.  
To determine the reporting requirements for individual SAEs, the sponsor will assess the 
expectedness of the SAEs using the following reference documents: 
 Pamiparib Investigator’s Brochure 
 Tislelizumab Investigator’s Brochure 
10.13 Special Precautions 
As a routine precaution, after infusion of tislelizumab on day 1 of cycle 1 and cycle 2, patients 
must be monitored for at least 1 hour afterwards in an area with resuscitation equipment and 
emergency agents.  From cycle 3 onward, a minimum of a 30-minute monitoring period is 
required in an area with resuscitation equipment and emergency agents.  
The management for tumor lysis syndrome, infusion-related reactions, severe hypersensitivity 
reactions, irAEs, and renal function abnormalities according to the NCI-CTCAE criteria are 
outlined in Sections 10.13.1, 10.13.2, 10.13.3, 10.13.4, and 10.13.5 respectively. 
10.13.1 
Tumor Lysis Syndrome 
A potential risk of tumor lysis syndrome (TLS) exists since tislelizumab can induce 
cytotoxicity. As recommended by Howard et al. [89], once TLS occurs, patients should be 
treated as per the local guidelines and the management algorithm (Figure 3). 
 

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Figure 3: Assessment and Initial Management of Tumor Lysis Syndrome 
 
 
 

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10.13.2 
Infusion-Related Reaction 
The symptoms of infusion-related reactions include fever, chills/rigor, nausea, pruritus, 
angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, 
dizziness or hypertension.  Severe reactions may include acute respiratory distress syndrome, 
myocardial infarction, ventricular fibrillation, and cardiogenic shock.  Patients should be 
closely monitored for such reactions. Immediate access to an Intensive Care Unit (ICU) or 
equivalent environment and appropriate medical therapy (including epinephrine, 
corticosteroids, IV antihistamines, bronchodilators, and oxygen) must be available to treat 
infusion-related reactions.   
Treatment modification for symptoms of infusion-related reactions due to study drug(s) is 
provided in Table 8.  
 
Table 8: Treatment Modification for Symptoms of Infusion-Related Reactions Due to 
Study Drug(s) 
NCI-CTCAE Grade 
Treatment Modification for Tislelizumab 
Grade 1 
Mild transient reaction; infusion interruption not 
indicated; intervention not indicated. 
Decrease infusion rate by 50%.  Any worsening is 
closely monitored.  Medical management as needed.  
Subsequent infusions should be given after 
premedication and at the reduced infusion rate.  
Grade 2 
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment (eg, 
antihistamines, NSAIDS, narcotics, IV fluids); 
prophylactic medications indicated for ≤ 24 hrs 
Stop infusion.  Infusion may be resumed at 50% of 
previous rate once infusion-related reactions has 
resolved or decreased to at least grade 1 in severity.  
Any worsening is closely monitored. Proper medical 
management should be instituted as described below.  
Subsequent infusions should be given after 
premedication and at the reduced infusion rate. 
Grade 3 – severe 
Prolonged (eg, not rapidly responsive to 
symptomatic medication and/or brief interruption of 
infusion); recurrence of symptoms following initial 
improvement; hospitalization indicated for clinical 
sequelae. 
Immediately stop the infusion.  Proper medical 
management should be instituted as described below. 
The patient should be withdrawn from study drug(s) 
treatment. 
Grade 4 – life threatening 
Life-threatening consequences; urgent intervention 
indicated. 
Immediately stop the infusion.  Proper medical 
management should be instituted as described below. 
The patient should be withdrawn from study drug(s) 
treatment. 
Hospitalization is recommended. 
Abbreviations: IV, intravenous; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for 
Adverse Event; NSAIDs, nonsteroidal anti-inflammatory drugs. 
 

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Once the tislelizumab infusion rate has been decreased by 50% or suspended due to an 
infusion-related reaction, it must remain decreased for all subsequent infusions with 
premedication.  If the patient has a second infusion-related reaction (≥ Grade 2) on the slower 
infusion rate, infusion should be discontinued and the patient should be withdrawn from 
tislelizumab treatment. 
CTCAE Grade 1 or 2 infusion reaction: Proper medical management should be instituted, 
as indicated per type of the reaction.  This includes but is not limited to an anti-histamine (eg, 
diphenhydramine or equivalent), anti-pyretic (eg, paracetamol or equivalent), and if considered 
indicated oral or IV glucocorticoids, epinephrine, bronchodilators, and oxygen.  In the next 
cycle, patients should receive oral premedication with an antihistamine (eg, diphenhydramine 
or equivalent) and an antipyretic (eg, paracetamol or equivalent), and they should be closely 
monitored for clinical signs and symptoms of an infusion reaction.  
CTCAE Grade 3 or 4 infusion reaction: Proper medical management should be instituted 
immediately, as indicated per type and severity of the reaction.  This includes but is not limited 
to oral or IV antihistamine, anti-pyretic, glucocorticoids, epinephrine, bronchodilators, and 
oxygen. 
10.13.3 
Severe Hypersensitivity Reactions and Flu-Like Symptoms 
If hypersensitivity reaction occurs, the patient must be treated according to the best available 
medical practice as described in the complete guideline for emergency treatment of 
anaphylactic reactions according to the Working Group of the Resuscitation Council (UK). 
[90, 91]  Patients should be instructed to report any delayed reactions to the investigator 
immediately. 
In the event of a systemic anaphylactic/anaphylactoid reaction (typically manifested within 
minutes following administration of the drug/antigen, and characterized by: respiratory 
distress; laryngeal edema; and/or intense bronchospasm; and often followed by vascular 
collapse or shock without antecedent respiratory difficulty; cutaneous manifestations such as 
pruritus and urticaria with/without edema; and gastrointestinal manifestations such as nausea, 
vomiting, crampy abdominal pain, and diarrhea), the infusion must be immediately stopped 
and the patient discontinued from the study. 
The patients will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed and then the patient should be placed on monitor 
immediately and ICU should be alerted for possible transfer if needed. 
For prophylaxis of flu-like symptoms, a dose of 25 mg indomethacin or a comparable dose of 
nonsteroidal anti-inflammatory drugs (ie, 600 mg ibuprofen, 500 mg naproxen sodium) may 
be administered 2 h before and 8 h after the start of each dose of study drugs(s) infusion.  

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Alternative treatments for fever (ie, paracetamol) may be given to patients at the discretion of 
the investigator. 
10.13.4 
Immune-Related Adverse Events (irAE) 
Immune-related AEs are of special interest in this study.  If the events listed below or similar 
events occur, the investigator should exclude alternative explanations (eg, combination drugs, 
infectious disease, metabolic, toxin, disease progression or other neoplastic causes) with 
appropriate diagnostic tests, which may include but is not limited to serologic, immunologic, 
and histologic (biopsy) data.  If alternative causes have been ruled out, the AE required the use 
of systemic steroids, other immunosuppressants, or endocrine therapy and is consistent with 
an immune mediated mechanism of action, the irAE indicator in the eCRF AE page should be 
checked. 
A list of potential irAEs is shown below in Table 9.  All conditions similar to those listed 
should be evaluated in patients receiving tislelizumab to determine whether they are immune-
related.  
Recommendation for diagnostic evaluation and management of irAEs is based on a recent 
ESMO guideline [92] and common immune-related toxicities are detailed in Appendix 10.  For 
any adverse events not included in Appendix 10, please refer to the recent ESMO guideline 
[92] for further guidance on diagnostic evaluation and management of immune-related 
toxicities.    
Table 9: Immune-Related Adverse Events 
Body System Affected 
Events 
Skin (mild-common) 
pruritus or maculopapular rash; vitiligo 
Skin (moderate) 
follicular or urticarial dermatitis; erythematous/lichenoid rash; Sweet’s 
syndrome 
Skin (severe-rare) 
full-thickness necrolysis/Stevens-Johnson syndrome 
Gastrointestinal 
colitis (includes diarrhea with abdominal pain or 
endoscopic/radiographic evidence of inflammation); pancreatitis; 
hepatitis; aminotransferase (ALT/AST) elevation; bowel perforation 
Endocrine 
thyroiditis, hypothyroidism, hyperthyroidism; hypophysitis with features 
of hypopituitarism, eg, fatigue, weakness, weight gain; insulin-
dependent diabetes mellitus; diabetic ketoacidosis; adrenal insufficiency 
Respiratory 
pneumonitis/diffuse alveolitis 
Eye 
episcleritis; conjunctivitis; iritis/uveitis 

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Neuromuscular 
arthritis; arthralgia; myalgia; neuropathy; Guillain-Barre syndrome; 
aseptic meningitis; myasthenic syndrome/myasthenia gravis, 
meningoencephalitis; myositis 
Blood 
anemia; leukopenia; thrombocytopenia 
Renal 
interstitial nephritis; glomerulonephritis; acute renal failure 
Cardiac 
pericarditis; myocarditis; heart failure 
 
If a toxicity does not resolve to ≤ Grade 1 within 12 weeks, study drug(s) should be 
discontinued after consultation with the Sponsor.  Patients who experience a recurrence of any 
event at the same or higher severity grade with rechallenge should permanently discontinue 
treatment unless the guidance in Appendices 10 and 11 allow continued treatment. 
For dose modifications of tislelizumab see Section 5.1.4. Please refer to Appendix 10 for 
guidance on managing immune-related adverse events.  For dose interruption and/or 
modification of pamiparib, please refer to Appendix 11.  
10.13.5 
Renal Function Abnormalities 
Patients with moderate renal dysfunction (estimated glomerular filtration rate > 30 mL/min 
and < 60 mL/min by Chronic Kidney Disease Epidemiology Collaboration equation) may be 
enrolled into the study.  The following algorithm is proposed for the use of steroid treatment 
in the management of irAEs: 
 If the serum creatinine is normal at baseline, please see Section 10.13.4 and refer to 
Appendix 10 for diagnosis and management of patients with abnormal renal 
laboratory values.  
 If the serum creatinine is Grade 1 at baseline and increase in serum creatinine meets 
criteria for serum creatinine increase ≥ Grade 2 after starting treatment with 
tislelizumab, refer to Appendix 10 for diagnosis and management of patients with 
abnormal renal laboratory values.  Check the estimated GFR using Appendix 18 and 
the eGFR calculator link.  In the setting of a Grade 2 serum creatinine increase only, 
study treatment can continue unless the serum creatinine increases by at least 50% 
from the baseline value OR the eGFR falls below 20 mL/min.  
 If the serum creatinine is Grade 2 at baseline and increase in serum creatinine meets 
criteria for serum creatinine increase ≥ Grade 3 after starting treatment with 
tislelizumab, refer to Appendix 10 for diagnosis and management of patients with 
abnormal renal laboratory values.  In the setting of a Grade 3 serum creatinine 
increase only, study treatment will be held until serum creatinine improves to baseline 
and treatment may resume only after discussion with the sponsor medical monitor.   
 

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11.0 
DATA ANALYSIS AND STATISTICAL 
CONSIDERATIONS 
11.1 Sample Size Considerations 
In Part A, the number of DLs examined and the emerging tislelizumab and pamiparib toxicities 
will determine the sample size. Five DLs are planned, and it is anticipated that up to 50 patients 
will be required to establish the RP2D of the combination.  
Part B will include expansion arms of specific tumor types. Up to approximately 200 patients 
may be enrolled.  The purpose of these expansion arms is to explore signals of clinical efficacy 
as well as to confirm the safety and tolerability of the combination in each selected tumor type. 
Anti-tumor activity will be evaluated in Part B. A decision can be made to stop an arm early 
due to suboptimal clinical anti-tumor activity.  All Arms will enroll approximately 20 patients.  
The sample size (n = 20) is determined such that the probability of observing at least one 
responder is approximately 88% in an expansion arm (n = 20) when the underlying ORR is as 
low as 10%. Each arm in Part B: 1a, 1b, 2, 3, 4, 5, 6, 7, 8, and 9 will be analyzed independently.  
All Arms will enroll approximately 20 patients with an option to increase each cohort to 40 
patients to confirm outcomes observed in the first 20 patients. 
Twenty additional patients may be enrolled in any disease cohort to evaluate further the anti-
tumor activity if evidence of activity is observed in the first 20 patients. Since a precise estimate 
of objective response rate is difficult to predict due to the heterogeneity of patients enrolled 
within each arm, a Bayesian predictive probability, which evaluates the statistical strength of 
the pamiparib plus tislelizumab combination regimen vs the standard chemotherapy, will be 
used to provide a guidance to decide whether to enroll additional 20 patients. For example, for 
an arm with historical response rate 10%, within the initial 20 patients, at least 2 responders 
should be observed to have a predictive probability of > 10% superiority over the 10% 
historical rate in a total of 50 patients; however, for an arm with higher response rate expected 
(eg, > 30% ORR in arm 1a), at least 6 responders are required to have a > 10% predictive 
probability in order to expand the arm beyond the initial 20 patients. 
11.2 General Considerations for Data Analysis 
Data will be listed and summarized using SAS® Version 9.3 or higher (SAS Institute, Inc., 
Cary, North Carolina) according to sponsor agreed reporting standards, where applicable. 
Complete details will be documented in the reporting and analysis plan. 
The following descriptive statistics will be used to summarize the trial data on the basis of their 
nature unless otherwise specified: 

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 Continuous variables: number of non-missing observations, mean, standard deviation, 
median, minimum, and maximum 
 Categorical variables: frequencies and percentages 
 Time-to-event variables: number of non-missing observations (N), median, minimum 
and maximum. Kaplan-Meier event rates may also be provided if applicable for specific 
time to event variables 
All data will be presented by part, then by dose level in Part A or by arm in Part B. Further 
description of the statistical methods and analyses will be provided in the statistical analysis 
plan. 
11.2.1 Analysis Populations 
All Patients Enrolled Set (ENR) 
The all patients (both parts) enrolled (ENR) set will include all patients who provide informed 
consent for this study. 
Safety Analysis Set (SAF) 
The safety analysis set (SAF) will include all patients (both parts) who received at least one 
dose of tislelizumab and/or pamiparib. The SAF analysis set will be used for all summaries 
(except DLTs). 
Efficacy Evaluable Set (EFF) 
The efficacy evaluable set (EFF) includes patients in the SAF who had measurable or evaluable 
disease at baseline including patients in the mCRPC aim whose disease progression can be 
evaluated by PSA and had at least one post baseline tumor assessment unless discontinued 
treatment due to clinical progression or death prior to tumor assessment. 
DLT Analysis Set (DLT) 
The DLT Analysis Set includes all patients who received at least 90% of tislelizumab and 75% 
of pamiparib or who experienced a DLT event during the DLT observation period (Cycle 1). 
PK Analysis Set (PKS) 
The PK Analysis Set will include patients in the Safety Analysis Set for whom at least one PK 
parameter can be derived for either pamiparib or tislelizumab. 
Exploratory Analyses 

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11.2.2 Data Analysis 
This study is a dose escalation and schedule expansion study. Safety, PK and 
pharmacodynamic, and efficacy data will be evaluated on an ongoing basis.  
11.2.3 Patient Disposition 
The number of patients enrolled, treated, discontinued from study drug and those with major 
protocol deviations will be counted. The primary reason for study drug discontinued will be 
summarized according to the categories in the eCRF. The end of study status (alive, dead, 
withdrew consent or lost to follow-up) at the data cutoff date will be summarized using the 
data from the eCRF. 
Major protocol deviations will be summarized and listed by each category (major or minor). 
11.2.4 Demographic and Other Baseline Characteristics 
Demographic and other baseline characteristics will be summarized in the safety analysis set 
using descriptive statistics. Continuous variables include age, weight, vital signs and time since 
initial and metastatic cancer diagnosis; categorical variables include, gender, ECOG, race, 
smoking status, TNM staging, metastatic site, and site of primary tumor. 
11.2.5 Prior and Concomitant Medication 
Concomitant medications will be assigned an 11-digit code using the WHO Drug Dictionary 
drug codes. Concomitant medications will be further coded to the appropriate Anatomical 
Therapeutic Chemical (ATC) code indicating therapeutic classification. Prior and concomitant 
medications will be summarized and listed by drug and drug class in the Clinical Study Report 
(CSR) for this protocol. Prior medications will be defined as medications that stopped before 
the first dose of study drug. Concomitant medications will be defined as medications that (1) 
started before the first dose of study drug and were continuing at the time of the first dose of 
study drug, or (2) started on or after the date of the first dose of study drug up to 30 days after 
the patient’s last dose. A listing of prior and concomitant medications will be included in the 
CSR of this protocol. 
11.3 Efficacy Analyses 
Response based on investigators’ judgment will be collected at screening and while on study 
approximately every 9 ± 1 weeks in the first 12 months and approximately 12 ± 1 weeks 

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thereafter in the simple form of four categories: PD, SD, CR, and PR (according to 
RECIST v1.1). 
For patients with ovarian, fallopian tube, or primary peritoneal cancer, investigators may also 
incorporate GCIG CA-125 response criteria [93], with RECIST Version 1.1 response criteria 
in assessing tumor response (refer to Appendix 4).  
For patients with prostate cancer, PCWG3 criteria [94] will also be used to evaluate PSA and 
modified RECIST responses (refer to Appendix 6). 
Anti-tumor activity of the combination therapy will be evaluated separately in each part in the 
safety analysis set. In Part B, efficacy variables (ie, ORR, DCR, CBR, PFS, DOR and OS) will 
be summarized by expansion arm using RECIST v1.1 when applicable. ORR, along with its 
95% confidence interval using exact method will be summarized. PFS will be summarized 
using Kaplan-Meier method. Kaplan-Meier curves will be shown by expansion arm. A 
waterfall plot of maximum tumor shrinkage from baseline will also be displayed. 
DCR, CBR, DOR and OS will be summarized using the methods as described above in the 
SAF. Efficacy endpoints will also be summarized in the efficacy evaluable set. 
To limit the number of patients who might be exposed to a less efficacious treatment, 
continuous monitoring of efficacy and safety will be implemented whenever possible during 
the trial. ORR in each arm will be calculated and compared to a historical rate. The enrollment 
of an expansion arm will be stopped early in case of low ORR such that any improvement over 
historical rate of single agent is unlikely. Due to the exploratory nature of the efficacy analysis, 
any early futility boundaries/criteria are advisory; and are to be used to aid the data 
interpretation only. Any decision made towards a particular arm during the Part B enrollment 
will be based on the totality of the data. 
11.4 Safety Analyses 
All patients who are exposed to (or started receiving) tislelizumab and/or pamiparib will be 
evaluated for safety. Safety data will be summarized by dose level. 
11.4.1 Dose Limited Toxicity 
For Part A, the number and proportion of patients experiencing DLTs will be reported by dose 
level, based on DLT observations during the first cycle. The DLT Analysis Set will be used 
for this analysis. There is no DLT analysis in Part B. 
11.4.2 Maximum Tolerated Dose 
The MTD is defined as the dose that produces an “acceptable” level of toxicity or that, if 
exceeded, would put patients at “unacceptable” risk for toxicity. The MTD for this study is 

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defined as the highest dose studied at which more than 2 in 3 to 6 patients has experienced a 
DLT in Cycle 1. If a MTD is identified, a dose level lower than MTD will be selected by SMC. 
11.4.3 Adverse Events 
In this protocol, a TEAE is defined as any AE or SAE with either an onset date or a date of 
worsening in severity from baseline (ie, pretreatment) occurring after first dose of study drug 
and up to either 30 days following discontinuation from study drugs or start of new anticancer 
therapy, whichever occurs first. The TEAE classification also applies to irAEs that are recorded 
up to 90 days after discontinuation from tislelizumab, regardless of initiation of subsequent 
anticancer therapy. Only those AEs that were treatment-emergent will be included in summary 
tables. All AEs, treatment-emergent or otherwise, will be presented in patient data listings. 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs 
by system organ class (SOC) and Preferred Term. A patient will be counted only once by the 
highest severity grade per NCI-CTCAE v4.03 [86] within an SOC and Preferred Term, even 
if the patient experienced more than 1 TEAE within a specific SOC and Preferred Term. The 
number (percentage) of patients with TEAEs will also be summarized by relationship to the 
study drug. 
Treatment-related AEs include those events considered by the Investigator to be related to 
study treatment or with missing assessment of the causal relationship. The SAEs, deaths, 
TEAEs with ≥ Grade 3 severity, irAEs, treatment-related TEAEs, and TEAEs that led to 
treatment discontinuation, dose interruption, dose reduction, or dose delay will be summarized. 
11.4.4 Laboratory Assessments 
Clinical laboratory (eg, hematology, serum chemistry) values will be evaluated for each 
laboratory parameter as appropriate. Abnormal laboratory values will be flagged as high or 
low relative to the normal range, where applicable. Descriptive summary statistics (eg, n, 
mean, standard deviation, median, minimum, maximum for continuous variables; n [%] for 
categorical variables) for laboratory parameters and their changes from baseline will be 
calculated. Laboratory values will be summarized by visit and by worst post-baseline visit. 
Laboratory parameters that are graded in CTCAE v.4.03 will be summarized by CTCAE grade. 
In the summary of laboratory parameters by CTCAE grade, parameters with CTCAE grading 
in both high and low directions (eg, calcium, glucose, magnesium, potassium, sodium) will be 
summarized separately. 
11.4.5 Electrocardiogram 
All ECG parameters including the QT interval corrected for heart rate (QTc) will be listed for 
each patient and summarized by dose level and assessment time. If sufficient data are available, 

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change from baseline will also be summarized. Relationship between dose level and QTc 
changes may be explored by graphs. QTc will be calculated using Fridericia’s formulae. 
11.4.6 Vital Signs 
Blood pressure, pulse, respiratory, temperature and weight will be summarized and listed. The 
change from baseline will also be displayed. 
11.4.7 Extent of Exposure 
Extent of exposure to each study drug will be summarized descriptively as the number of cycles 
received (number and percentage of patients), duration of exposure (days), cumulative total 
dose received per patient (mg), dose intensity, and relative dose intensity. 
The number (percentage) of patients requiring dose reduction, interruption, dose delay, and 
drug discontinuation due to AEs will be summarized for each study drug. Frequency of the 
above dose adjustments and discontinuation will be summarized by category.  
11.4.8 Physical Examination 
Physical examination results will be listed and summarized. 
11.4.9 Ophthalmologic Examination 
Ophthalmologic examination results will be listed and summarized. 
11.5 Pharmacokinetic Analyses 
In Part A of the study, PK parameters such as Cmax, Ctrough and Tmax for pamiparib may be 
derived for each cycle at which pharmacokinetics are to be measured; Ctrough may be derived 
for tislelizumab, where applicable (as specified in Table 4). In Part B of the study, PK 
parameters such as Ctrough may be derived for both pamiparib and tislelizumab for each cycle 
at which pharmacokinetics are to be measured, where applicable (as specified in Table 6). 
Additional PK analyses will be conducted as appropriate in all patients for whom valid 
tislelizumab and pamiparib PK parameters can be estimated. Nominal sampling times will be 
used for interim PK parameter calculations, while actual sampling times will be used in the 
final PK parameter calculations. 
Summary statistics of the calculated PK parameters will be provided. Graphical, non-
compartmental and 
 
 
 
  
 
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Possible DDIs between tislelizumab and pamiparib may be evaluated by comparison of the 
pharmacokinetic data generated in the present study and historical data. Significant differences 
in pharmacokinetic outcomes may be assessed for clinical relevance in consultation with the 
SMC (See Section 8.4.1) 
11.6 Biomarker Analyses 
 

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12.0 ETHICS 
12.1 Regulatory Authority Approval 
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency 
in accordance with any applicable country-specific regulatory requirements or file the protocol 
to the appropriate regulatory agency before the study is initiated at a study center in that 
country. 
12.2 Ethical Conduct of the Study and Ethics Approval 
This study will be conducted in full conformance with the ICH E6 guideline for Good Clinical 
Practice and the principles of the Declaration of Helsinki or the laws and regulations of the 
country in which the research is conducted, whichever affords the greater protection to the 
individual.  The study will comply with the requirements of the ICH E2A guideline (Clinical 
Safety Data Management: Definitions and Standards for Expedited Reporting). 
This protocol, the ICFs, any information to be given to the patient, and relevant supporting 
information must be submitted to the IRB/IEC by the principal investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.  In addition, any patient recruitment 
materials must be approved by the IRB/IEC.  
The principal investigator is responsible for providing written summaries of the status of the 
study to the IRB/IEC annually or more frequently in accordance with the requirements, 
policies, and procedures established by the IRB/IEC.  Investigators are also responsible for 
promptly informing the IRB/IEC of any protocol amendments.  In addition to the requirements 
for reporting all AEs to the sponsor, investigators must comply with requirements for reporting 
SAEs to the local health authority and IRB/IEC.  Investigators may receive written IND safety 
reports or other safety-related communications from the sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health authority 
requirements and the policies and procedures established by their IRB/IEC and archived in the 
site’s study file.  
12.3 Informed Consent 
The sponsor’s sample Informed consent(s) (ICF) will be provided to each site.  If applicable, 
it will be provided in a certified translation of the local language.  The final IRB/IEC-approved 
ICFs must be provided to the sponsor for health authority submission purposes according to 
local requirements.  
The ICFs must be signed and dated by the patient or the patient’s legally authorized 
representative before his or her participation in the study.  The case history or clinical records 

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for each patient shall document the informed consent process and that written informed consent 
was obtained prior to participation in the study.  
The ICFs will be revised whenever there are changes to study procedures or when new 
information becomes available that may affect the willingness of the patient to participate.  The 
final revised IRB-/IEC-approved Consent Forms must be provided to the sponsor for health 
authority submission purposes.  
Patients must be re-consented to the most current version of the ICFs (or to a significant new 
information/findings addendum in accordance with applicable laws and IRB/IEC policy) 
during their participation in the study.  For any updated or revised ICFs, the case history or 
clinical records for each patient shall document the informed consent process and that written 
informed consent was obtained using the updated/revised ICFs for continued participation in 
the study.  
A copy of each signed ICF must be provided to the patient or the patient’s legally authorized 
representative.  All signed and dated ICFs must remain in each patient’s study file or in the site 
file and must be available for verification by study monitors at any time.  
12.4 Handling of Clinically Significant Findings of Genomic Studies  
Any clinically significant results with familial implications (eg, a germline pathogenic 
mutation which confers an increased risk of developing disease) will be verified but the central 
laboratory and these results will be conveyed back to the treating investigator. The treating 
investigator will then contact the patient. The patient will not be informed of the result 
specifically but encouraged to contact the Familial Cancer Centre (FCC) for formal genetic 
counseling. The cancer genetics counseling service will facilitate a discussion regarding the 
potential implications of such genetic results to both participants and their families, allowing 
participants to make an informed choice to either (a) receive the results or (b) to opt not to 
receive any further information. The FCC will manage the participants with confirmed 
mutations and their families as per established clinical guidelines, or as deemed appropriate by 
the involved staff. If there are any areas which require additional clarification, the principle 
investigator, will approach the central Human Research Ethics Committee (HREC) to seek 
further guidance. 
Participants will be asked at the time of informed consent to nominate a next of kin to receive 
information regarding clinically meaningful results in the instance that the participant is no 
longer contactable, or deceased. Only germline research results that may be significant for 
family members will be returned to the next of kin. 

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12.5 Investigator Reporting Requirements 
As indicated in Section 10.12, the investigator (or sponsor, where applicable) is responsible 
for reporting SAEs to the IEC/IRB, in accordance with all applicable regulations. Furthermore, 
the investigator may be required to provide periodic safety updates on the conduct of the study 
at his/her study center and notification of study closure to the IEC/IRB. Such periodic safety 
updates and notifications are the responsibility of the investigator and not of the sponsor. 

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13.0 STUDY ADMINISTRATION 
13.1 Study and Study Center Closure 
Upon completion of the study, the monitor will conduct the following activities in conjunction 
with the investigator or study center personnel, as appropriate: 
 Return of all study data to the sponsor 
 Resolve and close all data queries 
 Accountability, reconciliation, and arrangements for unused investigational product(s) 
 Review of study records for completeness 
 Return of treatment codes to the sponsor 
 Shipment of PK and biomarker samples to assay laboratories 
In addition, the sponsor reserves the right to suspend or prematurely discontinue this study 
either at a single study center or at all study centers at any time for reasons including, but not 
limited to, safety or ethical issues or severe non-compliance. If the sponsor determines such 
action is needed, the sponsor will discuss this with the investigator (including the reasons for 
taking such action) at that time. When feasible, the sponsor will provide advance notification 
to the investigator of the impending action prior to it taking effect. 
The sponsor will promptly inform all other investigators and/or institutions conducting the 
study if the study is suspended or terminated for safety reasons, and will also inform the 
regulatory authorities of the suspension or termination of the study and the reason(s) for the 
action. If required by applicable regulations, the investigator must inform the IEC/IRB 
promptly and provide the reason for the suspension or termination. 
If the study is prematurely discontinued, all study data must be returned to the sponsor. In 
addition, arrangements will be made for all unused investigational product(s) in accordance 
with the applicable sponsor procedures for the study. 
Financial compensation to investigators and/or institutions will be in accordance with the 
agreement established between the investigator and the sponsor. 
13.2 Records Retention 
 
 
 
 

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13.3 Provision of Study Results and Information to Investigators 
 
 
 
 
 
 
 
13.4 Information Disclosure and Inventions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
13.4.1 Publication and Data Sharing Policy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  

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Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small cell 
lung cancer. N Engl J Med. 2015; 21;372(21):2018-28. 
82. 
Jiao S, Xia W, Yamaguchi H, et al. PARP inhibitor upregulates PD-L1 expression and 
enhances cancer-associated immunosuppression. Clin Cancer Res. 2017; Jul 
15;23(14):3711-3720. 
83. 
Marquard AM, Eklund AC, Joshi T, et al. Pan-cancer analysis of genomic scar 
signatures associated with homologous recombination deficiency suggests novel 
indications for existing cancer drugs. Biomark Res. 2015 May 1;3:9. 
84. 
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; Aug 14(9):882-92. 
85. 
FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and 
Inducers at 
http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/drugin
teractionslabeling/ucm093664.htm. 
86. 
Common Toxicity Criteria Version 4.03. Cancer Therapy Evaluation Program. June 
2010. 
87. 
Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy 
activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009; 
15(23): 7412-20. 
88. 
International Conference on Harmonisation. Note for Guidance on Good Clinical 
Practice E6 R2. November 2016. 
89. 
Howard, SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med. 2011; 
364(19): 1844-54. 

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90. 
Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--
guidelines for healthcare providers. Working Group of the Resuscitation Council (UK). 
Resuscitation. 2008;77(2):157-69. 
91. 
Resuscitation Council (UK). Emergency treatment of anaphylactic reactions.  Accessed 
from https://www.resus.org.uk/. 
92. 
Haanen J, Carbonnel F, Robert C, Kerr K, Peters S, Larkin J, Jordan K. Management 
of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, 
treatment and follow-up. Ann Oncol 2017; 28 (suppl 4): iv119–iv142. 
93. 
Rustin GJ, Vergote I, Eisenhauer E, et al., Definitions for response and progression in 
ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the 
Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011; 21(2): 419-23. 
94. 
Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-
Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer 
Clinical Trials Working Group 3. J ClinOncol. 2016 34:12, 1402-1418. 
95. 
International Committee of Medical Journal Editors. Recommendations for the 
Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. 
2016. Available online: http://www.icmje.org. Accessed 20 October 2017. 
96. 
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): 228-47. 

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15.0 APPENDICES 
APPENDIX 1: SIGNATURE OF INVESTIGATOR 
PROTOCOL TITLE: 
A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and 
Expansion Study to Investigate the Safety, Pharmacokinetics 
and Antitumor Activity of the anti-PD-1 Monoclonal Antibody 
BGB-A317 in combination with the PARP inhibitor BGB-290 
in Subjects with Advanced Solid Tumors 
PROTOCOL NO: 
 
BGB-A317/BGB-290_Study_001 
This protocol is a confidential communication of BeiGene Research and Development. I 
confirm that I have read this protocol, I understand it, and I will work according to this protocol. 
I will also work consistently with the ethical principles that have their origin in the Declaration 
of Helsinki and that are consistent with GCPs and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from BeiGene 
Research and Development. 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the 
name of the center in which the study will be conducted. Return the signed copy to BeiGene. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator: 
_______________________________ Date: _____________ 
Printed Name: 
_______________________________ 
Investigator Title: 
_______________________________ 
Name/Address of Center: 
_______________________________ 
 
_______________________________ 
 
_______________________________ 
 
_______________________________ 
 

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APPENDIX 2: CLINICAL LABORATORY ASSESSMENTS 
Clinical Chemistry 
Hematology 
Coagulation 
Urinalysis 
Alkaline phosphatase 
Hematocrit 
Prothrombin time 
Glucose 
Alanine aminotransferase 
Amylase 
Hemoglobin 
Activated Partial 
thromboplastin time 
Protein 
Aspartate aminotransferase 
Platelet counts 
International 
Normalized Ratio 
Ketones 
Albumin 
WBC 
count 
with 
differential 
 
Blood 
Total bilirubin 
Neutrophil count 
 
 
Blood urea nitrogen or urea 
Creatine 
Kinase 
(CK, 
including CK-MB)2 
Lymphocyte count 
 
 
Creatinine 
 
 
 
Glucose 
 
 
 
Lactate dehydrogenase 
Lipase 
 
 
 
Total protein 
 
 
 
Potassium 
 
 
 
Sodium 
 
 
 
Testosterone1 
 
 
 
Abbreviations: WBC: white blood cell. 
1  
Testosterone test is only applied for patients with mCRPC. However, the testosterone levels do not need to 
be checked if the patient has undergone surgical castration for > 4 months. Patients receiving chemical 
castration should have testosterone levels checked at baseline and confirmed to be in the castrate levels 
(< 0.5 ng/mL or 1.735 nM). 
2  
Include cardiac troponin I and T if CK-MB testing is not available 
 

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APPENDIX 3: EASTERN COOPERATIVE ONCOLOGY 
GROUP (ECOG) PERFORMANCE STATUS 
Grade Description 
0 
Fully active, able to carry on all pre-diseases performance without restriction. (Karnofsky 90-100) 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature (eg, light housework, office work). (Karnofsky 70-80) 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more 
than 50% of waking hours.  
(Karnofsky 50-60) 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
(Karnofsky 30-40) 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
(Karnofsky 10-20) 
5 
Dead (Karnofsky 0) 
 

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APPENDIX 4: EVALUATION OF RESPONSE ACCORDING 
TO CA-125 
The text below was obtained from the following reference: Rustin GJ, Vergote I, Eisenhauer 
E, et al. Definitions for Response and Progression in Ovarian Cancer Clinical Trials 
Incorporating RECIST 1.1 and CA 125 Agreed by the Gynecological Cancer Intergroup 
(GCIG). Int J Gynecology Cancer. 2011; 21(2): 419-423. [93] 
Definition of Response: 
A CA-125 response is defined as at least a 50% reduction in CA-125 levels from a pretreatment 
sample. The response must be confirmed and maintained for at least 28 days. Subjects can be 
evaluated according to CA-125 only if they have a pretreatment sample that is at least twice 
the upper limit of the reference range and within 2 weeks before starting the treatment. 
To calculate CA-125 responses accurately, the following rules apply: 
- 
Intervening samples and the 28-day confirmatory sample must be less than or equal to 
(within an assay variability of 10%) the previous sample. 
- 
Variations within the reference range of CA-125 levels will not interfere with the 
response definition. 
- 
For each subject, the same assay method must be used, and the assay must be tested in a 
quality control scheme. 
- 
Subjects are not evaluable by CA-125 if they have received mouse antibodies (unless the 
assay used has been shown not to be influenced by human anti-mouse antibody4, 5) or if 
there has been medical and/or surgical interference with their peritoneum or pleura during 
the previous 28 days (eg, paracentesis). If assessing therapy that includes 2 treatment 
modalities for relapse (eg, surgery and chemotherapy), any CA-125 response results from 
both treatment modalities. CA-125 cannot distinguish between the effects of the 2 
treatments. 
The date when the CA-125 level is first reduced by 50% is the date of the CA-125 response. 
To calculate response, an intent-to-treat analysis should be used that includes all subjects with 
an initial CA-125 level of at least twice the upper limit of the reference range as eligible and 
evaluable. In addition, as a separate analysis, those subjects who have a CA-125 response and 
whose CA-125 level falls to within the reference range can be classified as CA-125 complete 
responders. In Table 3, Table 4, Table 5, and Table 6 where CA-125 is stated as normalized or 
normal, this refers to being within the reference range. Subjects who have a decrease in CA-125 
to within the reference range, but whose initial CA-125 was less than twice the upper limit of 

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the reference range, are not considered to have had a CA-125 response and cannot therefore 
be classified as a CA-125 complete responder. 
Reporting of Response According to Both RECIST v1.1 and CA-125 Criteria 
Responses should be reported separately for both RECIST v1.1 and CA-125 response, as 
shown in the hypothetical example in below table: 
Example of Reporting RECIST, CA-125, and Combined Response 
RECIST 
CA-125 Response 
Yes 
No or PD 
N/E 
Total RECIST 
CR1 
4 
0 
0 
42 
PR 
3 
1 
1 
52 
SD 
3 
12 
1 
16 
PD 
0 
8 
2 
10 
NE 
3 
5 
2 
10 
Total CA-125 
13 
26 
6 
Total entered = 45 
1. *RECIST v1.1 includes normalization of CA-125 to achieve CR (Table 4 of this reference). 
2. In the above example, the RECIST v1.1 response rate is 9 (25.7%) of 35 RECIST v1.1 evaluable subjects, 
the CA-125 response rate is 13 (33%) of 39 CA125 evaluable subjects, and the combined overall response 
rate (either RECIST or CA-125 response) is 15 (35%) of 43. 
Note: Bolded numbers, CA-125 responders; bolded and italicized numbers, both RECIST and CA-125 
responders; italicized numbers, RECIST responders. 
 
 

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APPENDIX 5: EVIDENCE OF PROGRESSIVE DISEASE TO 
DETERMINE TRIAL ENTRY ELIGIBILITY IN 
PATIENTS WITH PROSTATE CANCER 
Patients being considered for trial entry should have evidence of disease progression by PSA, 
modified RECIST or bone scan to be eligible. 
PSA: PSA evidence of disease progression based on the prostate cancer working group 
(PCWG) 3 criteria consist of a minimum PSA level 2.0 ng/ml that has risen on at least 
2 successive occasions, at least 1 weeks apart. As shown in Figure below, the reference value 
# 1 is the last value before the rise in PSA was observed. If the confirmatory PSA value (# 3A) 
is greater than the screening value then progression by PSA is met and the patient is eligible 
for trial enrollment on the basis of PSA alone. If the confirmatory PSA (#3B) value is less 
than the screening PSA (#2) value, then an additional test for rising PSA (#4) will be required 
to document progression before the patient can be enrolled. 
 
 
Figure 1: Eligibility Based on PSA 
Target lesion/measurable disease: Patients are not required to have evidence of disease 
progression by measurable disease if they meet the criteria for disease progression on the basis 
of PSA or bone scan. Evidence of nodal or visceral disease progression however is sufficient 
for trial entry independent of PSA readings. Because lymph nodes may be enlarged due to 
benign pathology, only lymph nodes that are ≥ 2 cm should be used for disease evaluation. 
Bone scan: Evidence of disease progression based on bone scan appearance is sufficient for 
trial entry independent of PSA readings. If the appearance of the bone scan is the only 
indicator of progression then there must be ≥ 2 new bone lesions compared with the prior 

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bone scans. If there is ambiguity about the appearance of the bony lesions such as traumatic 
in nature or secondary to a flare reaction then it is recommended that an alternative imaging 
modality such as MRI or fine-cut CT be used to evaluate these lesions further. 
 

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APPENDIX 6: PROSTATE CANCER CLINICAL TRIALS 
WORKING GROUP 3 (PCWG3) CRITERIA TO GUIDE 
ASCRIBING DISEASE RESPONSE 
The table below is modified from the following reference: Scher HI, Morris MJ, Stadler WM, 
et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated 
Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J ClinOncol. 
2016 34:12, 1402-1418. [94] 
 
Variable 
PCWG3 (2016) 
PSA 
On this study serial PSA measurements will be done every 9 
weeks on day 1 of every 4th cycle. Increases and decreases will 
be tracked in order to assess disease response. The PSA 
readings on its own will not be used to define progression in 
this protocol. PSA response and PSA progression will be 
defined according to the consensus guidelines of the PCWG 3: 
 PSA partial response is defined as a ≥ 50% decline in PSA 
from Cycle1 Day1 (baseline) PSA value. This PSA decline 
much be confirmed to be sustained by a second PSA value 
obtained 4 or more weeks later. 
 PSA progression date is defined as the date that a ≥ 25% 
increase and an absolute increase of ≥ 2 ng/mL above the 
nadir is documented, which is confirmed by a second 
consecutive value obtained four or more weeks later. The 
first PSA reading will be obtained at week 12. 
Duration of PSA Response: 
Duration of PSA response is calculated from the time the PSA 
value first declines by at least 50% of the Cycle 1 Day 1 
(baseline) value that has been confirmed by a second value 
until the time there is an increase of 25% of PSA nadir, 
provided the absolute increase is at least 2 ng/mL. The increase 
must be confirmed by a second consecutive measurement that 
is at least 25% above the nadir. If the PSA never shows a 25% 
increase over the nadir value, then the subject will be assessed 
at the last PSA measurement. 

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Target Lesions 
Nodal or visceral progression sufficient for trial entry 
independent of PSA Measurable lesions not required for entry 
Use RECIST to record soft-tissue (nodal and visceral) lesions 
as target or non-target 
Only lymph nodes ≥ 2 cm in diameter should be used to assess 
for a change in size 
Record presence of nodal and/or visceral disease separately. 
Progression at any scheduled reassessment  12 weeks does not 
need to be confirmed 
Bone 
≥ 2 new lesions at the first scheduled reassessment from Cycle 1 
Day 1 compared with baseline must be confirmed by a second 
scan performed 6 or more weeks later.  
Confirmatory scans should show an additional 2 new lesions 
compared to the first post-treatment scan (ie, a total of ≥ 4 new 
lesions compared with the baseline bone scan).  
Confirm ambiguous results by other imaging modalities (eg, CT 
or MRI).  
Investigators are highly encouraged to maintain the subject’s 
treatment with study medication unless progression is 
confirmed. 
Abbreviations: PCWG3: Prostate Cancer Clinical Trials Working Group 3; PSA: prostate-
specific antigen; PSA-DT: PSA doubling-time; RECIST: Response Evaluation Criteria in 
Solid Tumors; CT: computed tomography; MRI: magnetic resonance imaging; PET: positron 
emission tomography 
 

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APPENDIX 8: THE RESPONSE EVALUATION CRITERIA IN 
SOLID TUMORS (RECIST) GUIDELINES 
The text below was obtained from the following reference: Eisenhauer EA, Therasse P, 
Bogaerts J, et al. New response evaluation criteria in solid tumors: revised RECIST guideline 
(Version 1.1). Eur J Cancer 2009;45: 228-247. [96]  
DEFINITIONS 
Response and progression will be evaluated in this trial using the international criteria proposed 
by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee (Version 1.1). 
Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are 
used in the RECIST criteria. Note: Lesions are either measurable or non-measurable using the 
criteria provided below. The term “evaluable” in reference to measurability will not be used 
because it does not provide additional meaning or accuracy. 
Measurable Disease 
Tumor lesions: Must be accurately measured in at least 1 dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
 10 mm by CT scan (irrespective of scanner type) and MRI (no less than double the slice 
thickness and a minimum of 10 mm). 
 10 mm caliper measurement by clinical exam (when superficial). 
 20 mm by chest X-ray (if clearly defined and surrounded by aerated lung). 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis 
will be measured and followed. 
Non-measurable Disease 
All other lesions (or sites of disease), including small lesions (longest diameter ≥ 10 to < 15 mm 
with conventional techniques or < 10 mm using spiral CT scan), are considered non-
measurable disease. Leptomeningeal disease, ascites, pleural, or pericardial effusion, 
inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical examination that is not measurable by 
reproducible imaging techniques are all non-measurable. 
Bone lesions: 

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 Bone scan, positron emission tomography (PET) scan, or plain films are not considered 
adequate imaging techniques to measure bone lesions. However, these techniques can 
be used to confirm the presence or disappearance of bone lesions. 
 Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as CT 
or MRI can be considered as measurable lesions if the soft tissue component meets the 
definition of measurability described above. 
 Blastic bone lesions are non-measurable. 
Cystic lesions: 
 Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they 
are, by definition, simple cysts. 
 Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if non-
cystic lesions are present in the same subject, these are preferred for selection as target 
lesions. 
Lesions with prior local treatment: 
 Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
locoregional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion. Trial protocols should detail the conditions 
under which such lesions would be considered measurable. 
Target Lesions 
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total should 
be identified as target lesions and recorded and measured at baseline. Target lesions should be 
selected on the basis of their size (lesions with the longest diameter), be representative of all 
involved organ, but in addition should be those that lend themselves to reproducible repeated 
measurements. 
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥ 15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as 2 dimensions in the plane in which 

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the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, saggital, or coronal). The smaller of these measures is the short axis. 
For example, an abdominal node which is reported as being 20 mm× 30 mm has a short axis 
of 20 mm and qualifies as a malignant, measurable node. In this example, 20 mm should be 
recorded as the node measurement. All other pathological nodes (those with short axis ≥ 10 mm 
but < 15 mm) should be considered non-target lesions. Nodes that have a short axis < 10 mm 
are considered non-pathological and should not be recorded or followed. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression 
in the measurable dimension of the disease. 
Non-target Lesions 
All other lesions (or sites of disease) including pathological lymph nodes should be identified 
as non-target lesions and should also be recorded at baseline. Measurements are not required 
and these lesions should be followed as “present”, “absent”, or in rare cases “unequivocal 
progression” (more details to follow). In addition, it is possible to record multiple non-target 
lesions involving the same organ as a single item on the case record form (eg, “multiple 
enlarged pelvic lymph node” or “multiple liver metastases”). 
GUIDELINES FOR EVALUATION OF MEASURABLE DISEASE 
All measurements should be recorded in metric notation, using calipers if clinically assessed. 
All baseline evaluations should be performed as close as possible to the treatment start and 
never more than 4 weeks before the beginning of the treatment. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging based evaluation 
should always be done rather than clinical examination unless the lesion(s) being followed 
cannot be imaged but are assessable by clinical examination. 
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial 
and P10 mm diameter as assessed using calipers (eg, skin nodules). For the case of skin lesions, 
documentation by color photography including a ruler to estimate the size of the lesion is 
suggested. As noted above, when lesions can be evaluated by both clinical examination and 
imaging, imaging evaluation should be undertaken since it is more objective and may also be 
reviewed at the end of the trial. 
Chest X-ray: Chest CT is preferred over chest X-ray, particularly when progression is an 
important endpoint, since CT is more sensitive than X-ray, particularly in identifying new 

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lesions. However, lesions on chest X-ray may be considered measurable if they are clearly 
defined and surrounded by aerated lung. 
CT, MRI: CT is the best currently available and reproducible method to measure lesions 
selected for response assessment. This guideline has defined measurability of lesions on CT 
scan based on the assumption that CT slice thickness is 5 mm or less. When CT scans have 
slice thickness greater than 5 mm, the minimum size for a measurable lesion should be twice 
the slice thickness. MRI is also acceptable in certain situations (eg, for body scans). 
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to 
the next. If new lesions are identified by ultrasound in the course of the study, confirmation by 
CT or MRI is advised. If there is concern about radiation exposure at CT, MRI may be used 
instead of CT in selected instances. 
Endoscopy, laparoscopy: The utilization of these techniques for objective tumor evaluation is 
not advised. However, they can be useful to confirm complete pathological response when 
biopsies are obtained or to determine relapse in trials where recurrence following CR or 
surgical resection is an endpoint. 
Tumor markers: Tumor markers alone cannot be used to assess objective tumor response. If 
markers are initially above the upper normal limit, however, they must normalize for a subject 
to be considered in CR. Because tumor markers are disease specific, instructions for their 
measurement should be incorporated into protocols on a disease specific basis. Specific 
guidelines for both CA-125 response (in recurrent ovarian cancer) and PSA response (in 
recurrent prostate cancer), have been published. In addition, the Gynecologic Cancer 
Intergroup has developed CA-125 progression criteria which are to be integrated with objective 
tumor assessment for use in first-line trials in ovarian cancer. 
Histology: These techniques can be used to differentiate between PR and CR in rare cases if 
required by protocol (for example, residual lesions in tumor types such as germ cell tumors, 
where known residual benign tumors can remain). When effusions are known to be a potential 
adverse effect of treatment (eg, with certain taxane compounds or angiogenesis inhibitors). 
RESPONSE CRITERIA 
Evaluation of Target Lesions 
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-
target) must have reduction in short axis to < 10 mm. 

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Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking 
as reference the baseline sum diameters. 
Progressive Disease (PD): At least a 20% increase in the sum of 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. 
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. 
Lymph nodes: Lymph nodes identified as target lesions should always have the actual short 
axis measurement recorded (measured in the same anatomical plane as the baseline 
examination), even if the nodes regress to below 10 mm on study. This means that when lymph 
nodes are included as target lesions, the “sum” of lesions may not be zero even if CR criteria 
are met, since a normal lymph node is defined as having a short axis of < 10 mm. Case report 
recorded in a separate section where, in order to qualify for CR, each node must achieve a short 
axis < 10 mm. For PR, SD and PD, the actual short axis measurement of the nodes is to be 
included in the sum of target lesions. 
Target lesions that become “too small to measure”: While on study, all lesions (nodal and non-
nodal) recorded at baseline should have their actual measurements recorded at each subsequent 
evaluation, even when very small (eg, 2 mm). However, sometimes lesions or lymph nodes 
which are recorded as target lesions at baseline become so faint on CT scan that the radiologist 
may not feel comfortable assigning an exact measure and may report them as being “too small 
to measure”. When this occurs it is important that a value be recorded on the eCRF. If it is the 
opinion of the radiologist that the lesion has likely disappeared, the measurement should be 
recorded as 0 mm. If the lesion is believed to be present and is faintly seen but too small to 
measure, a default value of 5 mm should be assigned (Note: It is less likely that this rule will 
be used for lymph nodes since they usually have a definable size when normal and are 
frequently surrounded by fat such as in the retroperitoneum; however, if a lymph node is 
believed to be present and is faintly seen but too small to measure, a default value of 5 mm 
should be assigned in this circumstance as well). This default value is derived from the 5 mm 
CT slice thickness (but should not be changed with varying CT slice thickness). The 
measurement of these lesions is potentially non-reproducible; therefore providing this default 
value will prevent false responses or progressions based upon measurement error. To reiterate, 
however, if the radiologist is able to provide an actual measure, that should be recorded, even 
if it is below 5 mm. 
Lesions that split or coalesce on treatment: When non-nodal lesions “fragment”, the longest 
diameters of the fragmented portions should be added together to calculate the target lesion 

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sum. Similarly, as lesions coalesce, a plane between them may be maintained that would aid 
in obtaining maximal diameter measurements of each individual lesion. If the lesions have 
truly coalesced such that they are no longer separable, the vector of the longest diameter in this 
instance should be the maximal longest diameter for the “coalesced lesion”. 
Evaluation of Non-target Lesions 
While some non-target lesions may actually be measurable, they need not be measured and 
instead should be assessed only qualitatively at the time points specified in the protocol. 
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD): Unequivocal progression (see comments below) of existing non-
target lesions. 
When the subject also has measurable disease: In this setting, to achieve “unequivocal 
progression” on the basis of the non-target disease, there must be an overall level of substantial 
worsening in non-target disease such that, even in presence of SD or PR in target disease, the 
overall tumor burden has increased sufficiently to merit discontinuation of therapy. A modest 
“increase” in the size of one or more non-target lesions is usually not sufficient to qualify for 
unequivocal progression status. The designation of overall progression solely on the basis of 
change in non-target disease in the face of SD or PR of target disease will therefore be 
extremely rare. 
When the subject has only non-measurable disease: This circumstance arises in some Phase 3 
trials when it is not a criterion of trial entry to have measurable disease. The same general 
concept apply here as noted above, however, in this instance there is no measurable disease 
assessment to factor into the interpretation of an increase in non-measurable disease burden. 
Because worsening in non-target disease cannot be easily quantified (by definition: if all 
lesions are truly non-measurable) a useful test that can be applied when assessing subjects for 
unequivocal progression is to consider if the increase in overall disease burden based on the 
change in non-measurable disease is comparable in magnitude to the increase that would be 
required to declare PD for measurable disease: ie, an increase in tumor burden representing an 
additional 73% increase in “volume” (which is equivalent to a 20% increase diameter in a 
measurable lesion). Examples include an increase in a pleural effusion from “trace” to “large”, 
an increase in lymphangitic disease from localized to widespread, or may be described in 
protocols as “sufficient to require a change in therapy”. If “unequivocal progression” is seen, 
the subject should be considered to have had overall PD at that point. While it would be ideal 

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to have objective criteria to apply to non-measurable disease, the very nature of that disease 
makes it impossible to do so, therefore the increase must be substantial. 
New Lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal: ie, not attributable to differences in scanning technique, change in imaging 
modality or findings thought to represent something other than tumor (for example, some 
“new” bone lesions may be simply healing or flare of pre-existing lesions). This is particularly 
important when the subject’s baseline lesions show PR or CR. For example, necrosis of a liver 
lesion may be reported on a CT scan report as a “new” cystic lesion, which it is not. 
A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. An example of this 
is the subject who has visceral disease at baseline and while on study has a CT or MRI brain 
ordered which reveals metastases. The subject’s brain metastases are considered to be evidence 
of PD even if he/she did not have brain imaging at baseline. 
If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm there 
is definitely a new lesion, then progression should be declared using the date of the initial scan. 
While FDG-PET (PET scanning with the tracer fluorine-18 [F-18]fluorodeoxyglucose [FDG]) 
response assessments need additional study, it is sometimes reasonable to incorporate the use 
of FDG-PET scanning to complement CT scanning in assessment of progression (particularly 
possible “new” disease). New lesions on the basis of FDG-PET imaging can be identified 
according to the following algorithm: 
 Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion. No FDG-PET at baseline and a positive FDG-PET at follow-
up: If the positive FDG-PET at follow-up corresponds to a new site of disease 
confirmed by CT, this is PD. If the positive FDG-PET at follow-up is not confirmed as 
a new site of disease on CT, additional follow-up CT scans are needed to determine if 
there is truly progression occurring at that site (if so, the date of PD will be the date of 
the initial abnormal FDG-PET scan). If the positive FDG-PET at follow-up 
corresponds to a pre-existing site of disease on CT that is not progressing on the basis 
of the anatomic images, this is not PD. 
Evaluation of Best Overall Response 

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The best overall response is the best response recorded from the start of the study drug 
treatment until the end of treatment taking into account any requirement for confirmation. On 
occasion a response may not be documented until after the end of therapy so protocols should 
be clear if post-treatment assessments are to be considered in determination of best overall 
response. Protocols must specify how any new therapy introduced before progression will 
affect best response designation. The subject’s best overall response assignment will depend 
on the findings of both target and non-target disease and will also take into consideration the 
appearance of new lesions. Furthermore, depending on the nature of the study and the protocol 
requirements, it may also require confirmatory measurement. Specifically, in non-randomized 
trials where response is the primary endpoint, confirmation of PR or CR is needed to deem 
either one the “best overall response”. 
The best overall response is determined once all the data for the subject is known. Best 
response determination in trials where confirmation of complete or partial response IS NOT 
required: Best response in these trials is defined as the best response across all time points (for 
example, a subject who has SD at first assessment, PR at second assessment, and PD on last 
assessment has a best overall response of PR). When SD is believed to be best response, it 
must also meet the protocol specified minimum time from baseline. If the minimum time is 
not met when SD is otherwise the best time point response, the subject’s best response depends 
on the subsequent assessments. For example, a subject who has SD at first assessment, PD at 
second and does not meet minimum duration for SD, will have a best response of PD. The 
same subject lost to follow-up after the first SD assessment would be considered unevaluable. 
 
Target Lesions 
Non-target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; NE: not evaluable 
 

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Note: When nodal disease is included in the sum of target lesions and the nodes decrease to 
“normal” size (< 10 mm), they may still have a measurement reported on scans. This 
measurement should be recorded even though the nodes are normal in order not to overstate 
progression should it be based on increase in size of the nodes. As noted earlier, this means 
that subjects with CR may not have a total sum of “zero” on the eCRF. 
In trials where confirmation of response is required, repeated ‘NE’ time point assessments may 
complicate best response determination. The analysis plan for the trial must address how 
missing data/assessments will be addressed in determination of response and progression. For 
example, in most trials it is reasonable to consider a subject with time point responses of PR-
NE-PR as a confirmed response. 
Subjects 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 objective progression 
even after discontinuation of treatment. Symptomatic deterioration is not a descriptor of an 
objective response: it is a reason for stopping trial therapy. 
Conditions that define “early progression, early death, and inevaluability” are trial specific and 
should be clearly described in each protocol (depending on treatment duration, treatment 
periodicity). 
In some circumstances it may be difficult to distinguish residual disease from normal tissue. 
When the evaluation of CR depends upon this determination, it is recommended that the 
residual lesion be investigated (fine needle aspirate/biopsy) before assigning a status of CR. 
FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy in cases 
where a residual radiographic abnormality is thought to represent fibrosis or scarring. The use 
of FDG-PET in this circumstance should be prospectively described in the protocol and 
supported by disease specific medical literature for the indication. However, it must be 
acknowledged that both approaches may lead to false positive CR due to limitations of FDG-
PET and biopsy resolution/ sensitivity. 
For equivocal findings of progression (eg, very small and uncertain new lesions; cystic 
changes, or necrosis in existing lesions), treatment may continue until the next scheduled 
assessment. If at the next scheduled assessment, progression is confirmed, the date of 
progression should be the earlier date when progression was suspected. 
CONFIRMATORY MEASUREMENT/DURATION OF RESPONSE 
Confirmation 
In non-randomized trials where response is the primary endpoint, confirmation of PR and CR 
is required to ensure responses identified are not the result of measurement error. This will also 

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permit appropriate interpretation of results in the context of historical data where response has 
traditionally required confirmation in such trials. However, in all other circumstances, ie, in 
randomized trials (Phase 2 or 3) or trials where stable disease or progression are the primary 
endpoints, confirmation of response is not required since it will not add value to the 
interpretation of trial results. However, elimination of the requirement for response 
confirmation may increase the importance of central review to protect against bias, in particular 
in trials which are not blinded. 
In the case of SD, measurements must have met the SD criteria at least once after trial entry at 
a minimum interval (in general not less than 6 weeks). 
Duration of Overall Response 
The duration of overall response is measured from the time measurement criteria are first met 
for CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively 
documented (taking as reference for PD the smallest measurements recorded on study). 
The duration of overall CR is measured from the time measurement criteria are first met for 
CR until the first date that recurrent disease is objectively documented. 
Duration of Stable Disease 
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for progression are met, taking as reference the smallest sum 
on study (if the baseline sum is the smallest, this is the reference for calculation of PD). 
The clinical relevance of the duration of stable disease varies in different studies and diseases. 
If the proportion of subjects achieving stable disease for a minimum period of time is an 
endpoint of importance in a particular trial, the protocol should specify the minimal time 
interval required between two measurements for determination of stable disease. 
Note: The DOR and stable disease as well as the progression-free survival are influenced by 
the frequency of follow-up after baseline evaluation. It is not in the scope of this guideline to 
define a standard follow-up frequency. The frequency should take into account many 
parameters including disease types and stages, treatment periodicity, and standard practice. 
However, these limitations of the precision of the measured endpoint should be taken into 
account if comparisons between studies are to be made. 
 

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APPENDIX 9: GUIDELINES FOR SUPPORTIVE CARE 
Subjects should receive appropriate supportive care measures as deemed necessary by the 
treating investigator including but not limited to the items outlined below: 
 Diarrhea: Subjects should be monitored 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). In symptomatic subjects, 
infectious etiologies should be ruled out, and if symptoms are persistent and/or sever, 
endoscopic evaluation should be considered. 
o In subjects with severe enterocolitis, BGB-A317 will be permanently 
discontinued and treatment with systemic corticosteroids should be initiated 
at a dose of 1 to 2 mg/kg/day of prednisone or equivalent. When symptoms 
improve to Grade 1 or less, corticosteroid taper should be started and 
continued over at least 1 month. 
o In subjects with moderate enterocolitis, BGB-A317 should be withheld and 
antidiarrheal treatment should be started. If symptoms are persistent for more 
than one week, systemic corticosteroids should be initiated (eg, 
0.5 mg/kg/day of prednisone or equivalent). When symptoms improve to 
Grade 1 or less, corticosteroid taper should be started and continued over at 
least 1 month. Regarding guidelines for continuing treatment with 
BGB-A317 see Protocol Section 5.1.4. 
 All subjects who experience diarrhea 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. 
 Nausea/vomiting: Nausea and vomiting should be treated aggressively, and 
consideration should be given in subsequent cycles to the administration of 
prophylactic antiemetic therapy according to standard institutional practice. Subjects 
should be strongly encouraged to maintain liberal oral fluid intake. 
 Anemia: Transfusions and/or erythropoietin may be utilized as clinically indicated for 
the treatment of anemia, but should be clearly noted as concurrent medications. 
 Neutropenia: Prophylactic use of colony-stimulating factors including granulocyte 
colony-stimulating factor (G-CSF), pegylated G-CSF or Granulocyte Macrophage 
Colony-Stimulating Factor (GM-CSF) is not allowed in this study. Therapeutic use of 
G-CSF is allowed in subjects with Grade 3-4 febrile neutropenia. 

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 Thrombocytopenia: Transfusion of platelets may be used if clinically indicated. 
Idiopathic thrombocytopenic purpura (ITP) should be ruled out before initiation of 
platelet transfusion. 
 Anti-infective: Subjects with a documented infectious complication should receive oral 
or IV antibiotics or other anti-infective agents as considered appropriate by the treating 
investigator for a given infectious condition, according to standard institutional 
practice. 
 Immune-related AEs: Subjects who develop a Grade 2 or higher irAEs (eg, colitis, skin 
rash, hepatitis, uveitis, hypo- or hyperthyroidism, hypophysitis, or any other), should 
be discussed immediately with the sponsor. Depending on the type and severity of an 
irAE, oral or intravenous treatment with a corticosteroid should be considered, in 
addition to appropriate symptomatic treatment of a given condition. 
 Infusion reaction: Infusion reactions may consist of fever, chills/rigor, nausea, pruritus, 
angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, 
dizziness or hypertension. Severe reactions may include acute respiratory distress 
syndrome, myocardial infarction, ventricular fibrillation, and cardiogenic shock. 
Subjects should be closely monitored for an infusion reaction during and immediately 
following drug infusion. 
o In the event of a Grade 1 or 2 infusion reaction, reduce the infusion rate by 
50% for the entire remaining duration of that infusion. Proper medical 
management should be instituted, as indicated per type of the reaction. This 
includes but is not limited to an anti-histamine (eg, diphenhydramine or 
equivalent), anti-pyretic (eg, paracetamol or equivalent), and if considered 
indicated oral or IV glucocorticoids, epinephrine, brochodilators, and 
oxygen. 
o In the event of a Grade 3 or 4 infusion reaction, immediately stop the 
infusion. Proper medical management should be instituted immediately, as 
indicated per type and severity of the reaction. This includes but is not 
limited to oral or IV antihistamine, anti-pyretic, glucocorticoids, 
epinephrine, bronchodilators, and oxygen. 
o Regarding continuation of study therapy after an infusion reaction has 
occurred; see the guidelines in Protocol Section 10.13.2. 

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APPENDIX 10: IMMUNE-RELATED ADVERSE EVENTS 
MANAGEMENT GUIDANCE FOR INVESTIGATORS 
The recommendations below for the diagnosis and management of any irAE are intended as a 
guidance.  This document should be used in conjunction with expert clinical judgement (by 
specialist physicians experienced in the treatment of cancer using immunological agents), and 
individual institutional guidelines or policies. 
Criteria used to diagnose irAEs include blood tests, diagnostic imaging, histopathology, and 
microbiology assessments to exclude alternative causes such as infection, disease progression, 
and adverse effects of concomitant drugs.  In addition to the results of these tests, the following 
factors should be considered when making an irAE diagnosis:  
 What was the temporal relationship between initiation of BGB-A317 and the adverse 
event? 
 How did the patient respond to withdrawal of BGB-A317? 
 Did the event recur when BGB-A317 was reintroduced? 
 Was there a clinical response to corticosteroids? 
 Is the event an autoimmune endocrinopathy? 
 Is disease progression or an alternative diagnosis a more likely explanation? 
When alternative explanations to autoimmune toxicity have been excluded, the irAE field, 
associated with the AE in the eCRF should be checked.  
Recommended Diagnostic Tests in the Management of Possible Immune-related 
Adverse Events 
Immune-related 
Toxicity 
Diagnostic Evaluation Guideline 
Thyroid Disorders 
Scheduled and repeat thyroid function tests (TSH and T4).  
Hypophysitis 
Check visual fields and consider pituitary endocrine axis blood profile.  
Perform pituitary and whole brain MRI in patients with headache, 
visual disturbance, unexplained fatigue, asthenia, weight loss and 
unexplained constitutional symptoms. 
Consider consultation with an endocrinologist if an abnormality is 
detected. 
Pneumonitis 
All patients presenting with new or worsened pulmonary symptoms or 
signs, such as an upper respiratory infection, new cough, shortness of 
breath or hypoxia should be assessed by high-resolution CT.  Consider 
pulmonary function test including DLCO.  

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Immune-related 
Toxicity 
Diagnostic Evaluation Guideline 
Radiographic appearance is often nonspecific.  Depending on the 
location of the abnormality, bronchoscopy and bronchoalveolar lavage 
or lung biopsy may be considered.  Consult with a respiratory 
medicine physician for cases of uncertain cause.  
Neurological Toxicity 
Perform a comprehensive neurological examination and brain MRI for 
all CNS symptoms; review alcohol history and other medications.  
Conduct a diabetic screen, and assess blood B12/folate, HIV status, 
TFTs, and consider autoimmune serology.  Consider the need for 
brain/spine MRI/MRA and nerve conduction study for peripheral 
neuropathy.  Consult with a neurologist if there are abnormal findings. 
Colitis 
Review dietary intake and exclude steatorrhea.  Consider 
comprehensive testing, including the following: FBC, UEC, LFTs, 
CRP, TFTs, stool microscopy and culture, viral PCR, Clostridium 
difficile toxin, cryptosporidia (drug-resistant organism).  
In case of abdominal discomfort, consider imaging, eg, X-ray, CT 
scan.  If a patient experiences bleeding, pain or distension, consider 
colonoscopy with biopsy and surgical intervention, as appropriate.  
Eye Disorders 
If patients experience new onset, acute or worsening eye 
inflammation, blurred vision or other visual disturbance, refer the 
patient urgently to an ophthalmologist for evaluation and management.  
Hepatitis 
Check ALT/AST/total bilirubin, INR/albumin; the frequency will 
depend on severity of the AE (eg, daily if Grade 3-4; every 2-3 days if 
Grade 2, until recovering).  Review medications (eg, statins, 
antibiotics) and alcohol and drug history.  Perform liver screen 
including Hepatitis A/B/C serology, Hepatitis E PCR and assess anti-
ANA/SMA/LKM/SLA/LP/LCI, iron studies.  Consider imaging, eg, 
ultrasound scan for metastases or thromboembolism.  Consult with a 
hepatologist. A liver biopsy is strongly encouraged for patient with 
Grade 3 or higher events.  
Renal toxicity 
Review hydration status, and medication history.  Test and culture 
urine.  Consider renal ultrasound scan, protein assessment 
(dipstick/24-hour urine collection), or phase-contrast microscopy.  
Refer to nephrology for further management assistance.  
Dermatology 
Consider other causes by conducting a physical examination, consider 
dermatology referral for skin biopsy. 
Rheumatology 
Conduct musculoskeletal history and perform complete rheumatology 
examination. Consider joint X-ray and other imaging as required to 
exclude metastatic disease. Perform autoimmune serology and refer to 
rheumatology for further management assistance.  

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Immune-related 
Toxicity 
Diagnostic Evaluation Guideline 
Joint or muscle 
inflammation 
Conduct musculoskeletal history and perform complete 
musculoskeletal examination. Consider joint X-ray and other imaging 
as required to exclude metastatic disease. Perform autoimmune 
serology and refer to rheumatology for further management assistance.  
For suspected myositis/rhabdomyolysis/myasthenia include: CK, ESR, 
CRP, troponin and consider a muscle biopsy. 
Myocarditis 
Perform ECG, echocardiogram, CK, CK-MB, troponin I and T 
analysis, and refer to a cardiologist. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate 
aminotransferase; CNS, central nervous system; CRP, C-reactive protein; CT, computed tomography; DLCO, 
diffusing capacity for carbon monoxide; FBC, full blood count; HIV, human immunodeficiency virus; INR, 
international normalized ratio; LCI, liver cytosolic antigen; LFT, liver function test; LKM, liver kidney 
microsomal antibody; LP, liver pancreas antigen; MRA, magnetic resonance angiogram; MRI, magnetic 
resonance imaging; PCR, polymerase chain reaction; SLA, soluble liver antigen; SMA, smooth muscle 
antibody; T4, thyroxine; TFT, thyroid function tests; TSH, thyroid-stimulating hormone; UEC,  urea 
electrolytes and creatinine. 
 
 

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Treatment of Immune-related Adverse Events 
 Immune-related AEs can escalate quickly; study treatment interruption, close 
monitoring, timely diagnostic work-up and treatment intervention, as appropriate, 
with patients is required 
 Immune-related AEs should improve promptly after introduction of 
immunosuppressive therapy.  If this does not occur, review the diagnosis, seek further 
specialist advice and contact the study medical monitor 
 For some Grade 3 toxicities that resolve quickly, rechallenge with study drug may be 
considered if there is evidence of a clinical response to study treatment, after 
consultation with the study medical monitor 
 Steroid dosages in the table below are for oral or intravenous (methyl)prednisolone.  
Equivalent dosages of other corticosteroids can be substituted.  For steroid-refractory 
irAEs, consider use of steroid-sparing agents (eg, mycophenolate mofetil [MMF]) 
 Budesonide may be substituted for prednisolone if considered standard of care.  
Prednisolone is preferred over prednisone, in the event that hepatic metabolic activity 
may be affected by the adverse event. 
 Consider prophylactic antibiotics for opportunistic infections if the patient is 
receiving long-term immunosuppressive therapy 
Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
Thyroid 
Disorders 
1-2 
Asymptomatic TFT 
abnormality or mild 
symptoms 
 
Replace thyroxine if hypothyroid, until 
TSH/T4 levels return to normal range. 
Thyrotoxic patients should be referred to 
an endocrinologist.  In cases with 
systemic symptoms: withhold study 
treatment, treat with a beta blocker and 
consider oral prednisolone 
0.5 mg/kg/day for thyroid pain.  Taper 
corticosteroids over 2-4 weeks. Monitor 
thyroid function regarding the need for 
hormone replacement. 
Continue study 
treatment or withhold 
treatment in cases with 
systemic symptoms. 
3-4 
Severe symptoms, 
hospitalization 
required 
Refer patient to an endocrinologist.   
If hypothyroid, replace with thyroxine 
0.5-1.6 µg/kg/day (for the elderly or 
those with co-morbidities, the suggested 
starting dose is 0.5 µg/kg/day).  Add oral 
prednisolone 0.5 mg/kg/day for thyroid 
pain.  Thyrotoxic patients require 
treatment with a beta blocker and may 
Hold study treatment; 
resume when 
resolved/improved to 
Grade 0-1. 

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
require carbimazole until thyroiditis 
resolves. 
Hypophysitis 
1-2 
Mild symptoms 
Refer patient to an endocrinologist for 
hormone replacement.  Add oral 
prednisolone 0.5-1 mg/kg/day for 
patients with pituitary inflammation. 
Taper corticosteroids over at least 
1 month.  If there is no improvement in 
48 hours, treat as Grade 3-4.  Taper 
corticosteroids over at least 1 month. 
Continue study 
treatment. 
3-4 
Moderate-severe 
symptoms 
Refer patient to an endocrinologist for 
assessment and treatment.  Initiate pulse 
IV methylprednisolone 1 mg/kg for 
patients with headache/visual 
disturbance due to pituitary 
inflammation.  Convert to oral 
prednisolone and taper over at least 1 
month.  Maintain hormone replacement 
according to endocrinology advice. 
Maintain hormone replacement 
according to endocrinology advice. 
Hold study treatment for 
patients with 
headache/visual 
disturbance due to 
pituitary inflammation 
until resolved/improved 
to Grade 2 or less. 
Discontinuation is 
usually not necessary. 
For France only, 
discontinue study 
treatment for Grade 4 
hypophysitis. 
Pneumonitis 
1 
Radiographic changes 
only 
Monitor symptoms every 2-3 days.  
If appearance worsens, treat as Grade 2. 
Consider holding study 
treatment until 
appearance improves 
and cause is determined. 
2 
Symptomatic: 
exertional 
breathlessness 
Commence antibiotics if infection 
suspected.  Add oral prednisolone 1 
mg/kg/day if symptoms/appearance 
persist for 48 hours or worsen.  Consider 
Pneumocystis infection prophylaxis.  
Taper corticosteroids over at least 
6 weeks. 
Consider prophylaxis for adverse steroid 
effects: eg, blood glucose monitoring, 
vitamin D/calcium supplement. 
Hold study treatment. 
Retreatment is 
acceptable if symptoms 
resolve completely or 
are controlled on 
prednisolone 
≤ 10 mg/day.  
Discontinue study 
treatment if symptoms 
persist with 
corticosteroid treatment. 

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
3-4 
Severe or 
life-threatening 
symptoms 
Breathless at rest 
Admit to hospital and initiate treatment 
with IV methylprednisolone 
2-4 mg/kg/day.  If there is no 
improvement, or worsening after 48 
hours, add infliximab 5 mg/kg (if no 
hepatic involvement).  Convert to oral 
prednisolone and taper over at least 2 
months.  Cover with empiric antibiotics 
and consider prophylaxis for 
Pneumocystis infection and other 
adverse steroid effects, eg, blood glucose 
monitoring, vitamin D/calcium 
supplement. 
Discontinue study 
treatment. 
Neurological 
Toxicity 
1 
Mild symptoms 
 
Continue study 
treatment. 
2 
Moderate symptoms 
Treat with oral prednisolone 0.5-1 
mg/kg/day.  Taper over at least 4 weeks. 
Obtain neurology consultation. 
Hold study treatment; 
resume when 
resolved/improved to 
Grade 0-1. 
3-4 
Severe/life-threatening 
Initiate treatment with oral prednisolone 
or IV methylprednisolone 1-2 
mg/kg/day, depending on symptoms.  
Taper corticosteroids over at least 1 
month.  
Consider azathioprine, MMF, 
cyclosporine if no response within 72-96 
hours 
Discontinue study 
treatment. 
Colitis / 
Diarrhea 
1 
Mild symptoms: 
< 3 liquid stool per 
day over baseline and 
feeling well 
Symptomatic management: fluids, 
loperamide, avoid high fiber/lactose diet. 
If Grade 1 persists for > 14 days manage 
as a Grade 2 event 
Continue study 
treatment. 
2 
Moderate symptoms: 
4-6 liquid stools per 
day over baseline, or 
abdominal pain, or 
blood in stool, or 
nausea, or nocturnal 
episodes 
Oral prednisolone 0.5 mg/kg/day (non-
enteric coated). 
Do not wait for any diagnostic tests to 
start treatment.  Taper steroids over 2-4 
weeks. Consider endoscopy if symptoms 
are recurring. 
Hold study treatment; 
resume when 
resolved/improved to 
baseline Grade.  

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
3 
Severe symptoms: 
> 6 liquid stools per 
day over baseline, or 
if episodic within 
1 hour of eating 
Initiate IV methylprednisolone 1-
2 mg/kg/day. 
Convert to oral prednisolone and taper 
over at least 4 weeks.  Consider 
prophylaxis for adverse steroid effects, 
eg, blood glucose monitoring, vitamin 
D/calcium supplement. 
If no improvement in 72 hours or 
symptoms worsen, consider infliximab 5 
mg/kg if no perforation, sepsis, TB, 
hepatitis, NYHA grade III/IV CHF or 
other immunosuppressive treatment: 
MMF or tacrolimus. 
Consult gastroenterologist to conduct 
colonoscopy/ sigmoidoscopy. 
Hold study treatment; 
retreatment may be 
considered when 
resolved/improved to 
baseline grade and after 
discussion with the 
study medical monitor. 
4 
Life-threatening 
symptoms 
Discontinue study 
treatment. 
Skin reactions 
1 
Skin rash, with or 
without symptoms, 
< 10% BSA 
Avoid skin irritants and sun exposure; 
topical emollients recommended. 
 
Continue study 
treatment. 
2 
Rash covers 10%-30% 
of BSA 
Avoid skin irritants and sun exposure; 
topical emollients recommended. 
Topical steroids (moderate strength 
cream once a day or potent cream twice 
daily) ± oral or topical antihistamines for 
itch. Consider a short course of oral 
steroids. 
Continue study 
treatment. 
3 
Rash covers > 30% 
BSA or Grade 2 with 
substantial symptoms 
Avoid skin irritants and sun exposure; 
topical emollients recommended. 
Initiate steroids as follows based on 
clinical judgement: 
 
For moderate symptoms: oral 
prednisolone 0.5-1 mg/kg/day for 
3 days then taper over 2-4 weeks. 
 
For severe symptoms: IV 
methylprednisolone 
0.5-1 mg/kg/day; convert to oral 
prednisolone and taper over at least 
4 weeks. 
Hold study treatment. 
Retreat when AE is 
resolved or improved to 
mild rash (Grade 1-2) 
after discussion with the 
study medical monitor. 
 
 

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
4 
Skin sloughing > 30% 
BSA with associated 
symptoms (eg, 
erythema, purpura, 
epidermal 
detachment) 
Initiate IV methylprednisolone 
1-2 mg/kg/day. Convert to oral 
prednisolone and taper over at least 4 
weeks. 
Admit to hospital and seek urgent 
dermatology consultation 
Discontinue study 
treatment. 
 
Hepatitis 
1 
ALT or AST > ULN 
to 3X ULN 
Check LFTs within 1 week; and before 
the next dose, check LFTs to verify that 
there has been no worsening. 
If LFTs are worsening, recheck every 
48-72 hours until improvement is seen. 
Continue study 
treatment if LFTs are 
unchanged or 
improving. 
Hold study treatment if 
LFTs are worsening 
until improvement is 
seen. 
2 
ALT or AST 3-5X 
ULN 
Recheck LFTs every 48-72 hours:   
For persistent ALT/AST elevation: 
consider oral prednisolone 0.5-1 
mg/kg/day for 3 days then taper over 2-4 
weeks. 
For rising ALT/AST: start oral 
prednisolone 1 mg/kg/day and taper over 
at least 4 weeks; re-escalate dose if LFTs 
worsen, depending on clinical 
judgement.  
Hold all study treatment 
and, treatment may be 
resumed when 
resolved/improved to 
baseline grade and 
prednisolone tapered to 
≤ 10 mg. 
Restart tislelizumab at 
200 mg IV Q3Weeks 
when transaminase 
levels return to baseline. 
Pamiparib may be 
started after 2 cycles of 
tislelizumab is tolerable. 
Restart pamiparib at 
20 mg orally twice daily. 
Dose increases to 40 mg 
orally twice daily may 
occur only if LFTs 
remain stable after 2 
cycles of treatment at 
20 mg dosing. 
 
3 
ALT or AST 5-20X 
ULN 
ALT/AST < 400 IU/L and normal 
bilirubin/INR/albumin: Initiate oral 
prednisolone 1 mg/kg and taper over at 
Permanently discontinue 
tislelizumab. Hold 
pamiparib until 
transaminase levels 

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
least 4 weeks. Recheck LFTs every 2 
days until improved. 
ALT/AST > 400 IU/L or raised 
bilirubin/INR/low albumin: Initiate IV 
(methyl)prednisolone 2 mg/kg/day.  
Check LFTs every day. When LFTs 
improve to Grade 2 or lower, convert to 
oral prednisolone and taper over at least 
4 weeks. 
return to baseline levels; 
reintroduce pamiparib 
only after discussion 
with the study medical 
monitor at a dose of 
20 mg orally twice daily. 
Dose escalation to 
40 mg orally twice daily 
may occur only if the 
LFTs remain stable after 
2 cycles of treatment at 
20 mg dosing. 
4 
ALT or AST > 20X 
ULN 
Initiate IV methylprednisolone 2 
mg/kg/day. Convert to oral prednisolone 
and taper over at least 6 weeks. 
Discontinue study 
treatment. 
Worsening LFTs despite steroids: 
· If on oral prednisolone, change to pulsed IV methylprednisolone 
· If on IV, add mycophenolate mofetil (MMF) 500-1000 mg twice daily 
· If worsens on MMF, consider addition of tacrolimus 
Duration and dose of steroid required will depend on severity of event 
Nephritis 
1 
Creatinine 1.5X 
baseline 
or > ULN to 1.5X 
ULN 
Repeat creatinine weekly. 
If symptoms worsen, manage as per 
criteria below. 
Continue study 
treatment. 
 
2 
Creatinine > 1.5-3X 
baseline or > 1.5-3X 
ULN 
Ensure hydration and review creatinine 
in 48-72 hours; if not improving, 
consider creatinine clearance 
measurement by 24-hour urine 
collection.  Discuss with nephrologist the 
need for kidney biopsy. 
If attributed to study drug, initiate oral 
prednisolone 0.5-1 mg/kg and taper over 
at least 2 weeks. 
Repeat creatinine/U&E every 48 hours. 
Hold study treatment. 
If not attributed to drug 
toxicity, restart 
treatment. 
If attributed to study 
drug and 
resolved/improved to 
Grade 0-1: Restart study 
drug if tapered to < 10 
mg prednisolone. 
3 
Creatinine > 3X 
baseline or > 3-6X 
ULN 
Hospitalize patient for monitoring and 
fluid balance; repeat creatinine every 24 
hours; refer to a nephrologist and discuss 
need for biopsy.  If worsening, initiate 
IV (methyl)prednisolone 1-2 mg/kg. 
Hold study treatment 
until the cause is 
investigated.  

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
Taper corticosteroids over at least 1 
month. 
If study drug suspected: 
Discontinue study 
treatment. 
4 
Creatinine > 6X ULN 
As per Grade 3, patient should be 
managed in a hospital where renal 
replacement therapy is available. 
Discontinue study 
treatment. 
Diabetes/ 
Hyperglycemia 
1 
Fasting glucose value 
ULN to 160 mg/dL; 
ULN to 8.9 mmol/L 
Monitor closely and treat according to local 
guideline. Checks for C-peptide and 
antibodies against glutamic acid 
decarboxylase and islet cells are 
recommended 
Continue Study Treatment. 
2 
Fasting glucose value 
160 - 250 mg/dL; 
8.9 - 13.9 mmol/L 
Obtain a repeat blood glucose level at least 
every week. Manage according to local 
guideline. 
Continue Study Treatment 
or hold treatment if 
hyperglycemia is 
worsening. Resume 
treatment when blood 
glucose is stabilized at 
baseline or Grade 0-1. 
3 
Fasting glucose value 
250 - 500 mg/dL; 
13.9 - 27.8 mmol/L 
Admit patient to hospital and refer to a 
diabetologist for hyperglycemia 
management. Corticosteroids may exacerbate 
hyperglycemia and should be avoided. 
Hold study treatment until 
patient is hyperglycemia 
symptom-free, and blood 
glucose has been stabilized 
at baseline or Grade 0-1. 
4 
Fasting glucose value 
> 500 mg/dL; 
> 27.8 mmol/L 
Admit patient to hospital and institute local 
emergency diabetes management. Refer the 
patient to a diabetologist for insulin 
maintenance and monitoring. 
Ocular Toxicity 
1 
Asymptomatic eye 
exam/test abnormality 
Consider alternative causes and prescribe 
topical treatment as required. 
Continue Study Treatment 
2 
Anterior uveitis or mild 
symptoms 
Refer patient to an ophthalmologist for 
assessment and topical corticosteroid 
treatment. Consider a course of oral steroids. 
Continue Study Treatment 
or hold treatment if 
symptoms worsen or if 
there are symptoms of 
visual disturbance 
3 
Posterior uveitis/ 
panuveitis or significant 
symptoms 
Refer patient urgently to an ophthalmologist. 
Initiate oral prednisolone 1-2 mg/kg and 
taper over at least 4 weeks. 
Hold study treatment until 
improved to Grade 0-1; 
reintroduce only after 
discussion with the study 
medical monitor. 
4 
Initiate IV (methyl)prednisolone 
2 mg/kg/day. Convert to oral prednisolone 
and taper over at least 4 weeks 
Discontinue study 
treatment 

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
Blindness (at least 
20/200) in the affected 
eyes 
Pancreatitis 
2 
Asymptomatic, blood 
test abnormalities 
Monitor pancreatic enzymes 
Continue study treatment  
3 
Abdominal pain, nausea 
and vomiting 
Admit to hospital for urgent management. 
Initiate IV (methyl)prednisolone 1-
2 mg/kg/day. Convert to oral prednisolone 
when amylase/lipase improved to Grade 2, 
and taper over at least 4 weeks 
Hold study treatment; 
reintroduce only after 
discussion with the study 
medical monitor. 
4 
Acute abdominal pain, 
surgical emergency 
Admit to hospital for emergency 
management and appropriate referral.  
Discontinue study 
treatment 
Arthritis 
1 
Mild pain with 
inflammation, swelling 
Management per local guideline.  
Continue study treatment 
2 
Moderate pain with 
inflammation, swelling, 
limited instrumental 
(fine motor) activities 
Management as per local guideline.  
Consider referring patient to a 
rheumatologist. If symptoms worsen on 
treatment, manage as a Grade 3 event. 
Continue treatment or, if 
symptoms continue 
worsens, hold study 
treatment until symptoms 
improve to baseline or 
Grade 0-1 
3 
Severe pain with 
inflammation or 
permanent joint damage, 
daily living activity 
limited 
Refer patient urgently to a rheumatologist for 
assessment and management. Initiate oral 
prednisolone 0.5-1 mg/kg and taper over at 
least 4 weeks. 
Hold study treatment 
unless improved to Grade 
0-1; reintroduce only after 
discussion with the study 
medical monitor. 
Mucositis/ 
stomatitis 
1 
Test findings only or 
minimal symptoms 
Consider topical treatment or analgesia as 
per local guideline 
Continue study treatment 
2 
Moderate pain, reduced 
oral intake, limited 
instrumental activities 
As per local guideline, treat with analgesics, 
topical treatments and oral hygiene care. 
Ensure adequate hydration. If symptoms 
worsen or there is sepsis or bleeding, manage 
as Grade 3. 
Continue study treatment 
3 
Severe pain, limited 
food and fluid intake, 
daily living activity 
limited  
Admit to hospital for appropriate 
management. Initiate IV 
(methyl)prednisolone 1-2 mg/kg/day. 
Convert to oral prednisolone when symptoms 
Hold study treatment until 
improved to Grade 0-1. 

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Autoimmune 
Toxicity 
Grade 
Treatment Guidelines (Subject to 
Clinical Judgement) 
Study Drug 
Management 
improved to Grade 2 and taper over at least 
4 weeks 
4 
Life-threatening 
complications or 
dehydration 
Admit to hospital for emergency care. 
Consider IV corticosteroids if not 
contraindicated by infection 
Discontinue study 
treatment 
Myositis/ 
Rhabdomyolysis 
1 
Mild weakness 
with/without pain 
Prescribe analgesics. 
If CK is significantly elevated and patient 
has symptoms, consider oral steroids and 
treat as Grade 2 
Continue study treatment. 
 
2 
Moderate weakness 
with/without pain 
If CK is 3 X ULN or worse initiate oral 
prednisolone 0.5-1 mg/kg and taper over at 
least 4 weeks 
Hold study treatment until 
improved to Grade 0-1 
 
3-4 
Severe weakness, 
limiting self-care 
Admit to hospital and initiate oral 
prednisolone 1 mg/kg. Consider bolus IV 
(methyl)prednisolone and 1-2 mg/kg/day 
maintenance for severe activity restriction or 
dysphagia. If symptoms do not improve add 
immunosuppressant therapy. Taper oral 
steroids over at least 4 weeks 
Hold study treatment until 
improved to Grade 0-1. 
Discontinue if any 
evidence of myocardial 
involvement 
Myocarditis 
1 
Asymptomatic but 
abnormal CK-MB, 
cardiac troponin or 
intraventricular 
conduction delay 
Admit to hospital and refer to a cardiologist. 
Transfer all patients with moderate/severe 
cardiac symptoms or any increase in cardiac 
serum markers to the coronary care unit. 
Initiate oral prednisolone or IV 
(methyl)prednisolone at 1-2 mg/kg/day. 
Manage symptoms of cardiac failure 
according to local guidelines. 
If no immediate response change to pulsed 
doses of (methyl)prednisolone 1 g/day and 
add MMF, infliximab or anti-thymocyte 
globulin 
Hold study treatment until 
completely resolved or 
myocarditis has been ruled 
out. 
 
2 
Symptoms on mild-
moderate exertion 
Discontinue study 
treatment unless cardiac 
involvement has been 
excluded and symptoms 
have completely resolved 
 
3-4 
Severe symptoms with 
exertion 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSA, body 
surface area; CHF, congestive heart failure; CK, creatine kinase; CK-MB, creatine kinase cardiac isoenzyme 
INR, international normalized ratio; IV, intravenous; LFT, liver function test; MMF, mycophenolate mofetil; 
NYHA, New York Heart Association; T4, thyroxine; TB, tuberculosis; TFT, thyroid function test; TSH, 
thyroid-stimulating hormone; U&E, urea and electrolytes; ULN, upper limit of normal. 
 

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APPENDIX 11: CRITERIA FOR INTERRUPTION AND RE-
INITIATION OF PAMIPARIB 
Criteria for treatment modifications and suggested guidelines for the management of some 
toxicities related to pamiparib are summarized below. These general guidelines may be 
modified at the discretion of the investigator based on best clinical judgment at that time. 
Any toxicities related to pamiparib should be managed according to standard medical 
practice. 
Dosing of pamiparib can be withheld for up to 28 days consecutively. If drug is planned to be 
held > 28 days, the medical monitor should be contacted before permanent patient 
discontinuation from the study drug. 
Criteria for treatment modifications and suggested guidelines for the management of some 
toxicities related to pamiparib are summarized below. These general guidelines may be 
modified at the discretion of the investigator based on discussions with the medical monitor 
and the best clinical judgment at that time; any decisions should be documented. Any 
toxicities related to pamiparib should be managed according to standard medical practice. 
A maximum of one dose reduction is allowed before the patient is permanently withdrawn 
from pamiparib administration. Dose levels for pamiparib are in 20 mg increments and are 
summarized in the Table below. 
Dose Levels for Pamiparib 
Dose Level 
Pamiparib 
1 
40 mg orally twice daily or  
60 mg orally twice daily 
-1 
20 mg orally twice daily 
40 mg orally twice daily 
After discussions with the medical monitor, pamiparib may be dose-reduced for a maximum of 2 dose reductions.  
 
A dose reduction will be made in a 20 mg increment.  For example, pamiparib 40 mg orally 
twice daily will be dose reduced to 20 mg orally twice daily for any NCI CTCAE Grade ≥2 
hematologic toxicity. If pamiparib 20 mg orally twice daily is not tolerable, then pamiparib 
should be discontinued. 
Specific guidance for the treatment of anemia includes: 
Adverse events of anemia with NCI CTCAE Grade 1 or 2 (Hb ≥ 8 g/dL) should be 
investigated and managed as deemed appropriate by the investigator with or without 
interruption of study drug or change in dose, taking into account previous history of anemia. 
Common treatable causes of anemia (eg, iron, vitamin B12, or folate deficiencies, and 

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hypothyroidism) should be investigated and appropriately managed. In some cases, 
management of anemia may require blood transfusions.  
If a patient develops anemia with CTCAE Grade 3 (Hb < 8g/dL) or worse, study treatment 
should be interrupted for up to maximum of 3 weeks.  
Study treatment can be restarted at the same dose if Hb has recovered to Grade 2 or better, ie, 
≥ 8 g/dL. Any subsequently required anemia-related interruptions, considered likely to be 
dose related, or coexistent with newly developed neutropenia, and or thrombocytopenia, will 
require pamiparib dose reductions to 20 mg orally twice daily. 
If a patient has been treated for anemia with multiple blood transfusions and becomes blood 
transfusion dependent as judged by investigator, pamiparib study treatment should be 
discontinued. 
Pamiparib will be dose-modified as outlined in the Table below. 
Recommended dose modifications for Pamiparib 
Toxicity 
Recommended Dose Modificationa 
Hematologic 
Anemia (Hgb) 
Grade 2 (Hgb < 10 - 8 g/dL) 
 
Only applies to patients with 
≤ Grade 1 at baseline 
First occurrence: continue dosing at current dose level 
Second and subsequent occurrences: hold pamiparib until resolved to ≤ Grade 1 
or baseline 
 If resolved ≤ 14 days, then maintain dose levels 
 If resolved > 14 days, then  pamiparib by 1 dose level 
Grade 3 (Hgb < 8 g/dL) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline 
 If resolved ≤ 14 days, then maintain dose levels 
 If resolved > 14 days, then  pamiparib by 1 dose level 
Grade 4 (life-threatening 
consequences; urgent intervention 
indicated) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
Neutropenia (ANC) 
Grade 3 (ANC < 1.0 - 0.5  109/L) 
Hold pamiparib until resolved to ≤ Grade 2 or baseline 
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 4 (ANC < 0.5  109/L) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
Febrile neutropenia (ANC < 1.0  
109/L with single temperature of 
> 38.3°C or sustained temperature 
of ≥ 38°C for > 1 hour) 
Hold pamiparib until resolved and 
 pamiparib by 1 dose level 

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Toxicity 
Recommended Dose Modificationa 
Thrombocytopenia (PLT) 
Grade 3 (PLT < 50 - 25  109/L) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline  
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 4 (PLT < 25  109/L) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
Renal 
Serum creatinine 
 
2-3  ULN 
Hold pamiparib until resolved to ≤ Grade 1 or baseline  
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 3 (> 3.0 - 6.0  ULN) 
and 
Grade 4 (> 6.0  ULN) 
Permanently discontinue pamiparib  
Hepatic 
Bilirubin 
 
Grade 2 (> 1.5 - 3.0  ULN) 
and 
Grade 3 (> 3.0 - 10.0  ULN) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline  
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 4 (> 10.0  ULN) 
Permanently discontinue pamiparib  
Note: If Grade 3 or 4 hyperbilirubinemia is due to the indirect (unconjugated) 
component only, and hemolysis as the etiology has been ruled out as per 
institutional guidelines (eg, review of peripheral blood smear and haptoglobin 
determination), then  pamiparib by 1 dose level and continue treatment at the 
discretion of the investigator in discussion with the medical monitor 
AST and/or ALT 
Grade 3 (> 5 and ≤ 20  ULN) 
 
 
 Hold pamiparib until transaminase levels have resolved and the 
prednisolone doses are consistent with replacement corticosteroid doses 
(< 10 mg). Restart pamiparib only after discussion with medical monitor at 
a dose of 20 mg orally twice daily.  
Grade 4 (> 20  ULN) 
Permanently discontinue pamiparib  
Pancreatic 
Pancreatitis 
Grade 3 or 4 
Permanently discontinue pamiparib  
Cardiac 
Cardiac - Prolonged QTc interval 

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Toxicity 
Recommended Dose Modificationa 
QTcF > 500 msec 
 Obtain triplicate ECGs (2 to 3 minutes apart) ~1 hour after initial ECG  
 If mean QTcF > 500 ms, hold pamiparib until evaluation of ECGs by 
cardiologist  
o Cardiology evaluation as soon as practical but within 7 days of initial 
abnormal ECG  
 If mean QTcF > 500 ms confirmed by cardiologist, permanently 
discontinue pamiparib  
Cardiac - General 
Grade 3 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib 1 dose level 
Grade 4 
Permanently discontinue pamiparib  
Other adverse events 
Grade 3 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
No dose reduction required for asymptomatic laboratory abnormalities 
Grade 4 
Permanently discontinue pamiparib  
Abbreviations: ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; 
ECG, electrocardiogram; Hgb, hemoglobin; PD, progressive disease; PLT, platelet (count); QTcF, QT interval 
corrected for heart rate using Fridericia’s formula; ULN, upper limit of normal. 
a. 
Dosing of pamiparib can be withheld for up to 28 days consecutively.  
 

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APPENDIX 12: PROHIBITED MEDICATIONS (STRONG 
AND MODERATE CYP3A INHIBITORS AND STRONG 
CYP3A INDUCERS  
 
Strong CYP3A Inhibitors 
Antibiotics: clarithromycin, telithromycin, troleandomycin 
Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole 
Antivirals: boceprevir, telaprevir 
Other: cobicistat, conivaptan, elvitegravir, mibefradil, nefazodone 
Protease inhibitors: indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir 
 
Strong CYP3A Inducers 
Avasimibe, carbamazepine, mitotane, phenobarbital, phenytoin, rifabutin, rifampin (rifampicin), St. John’s 
wort (Hypericum perforatum) 
 
Moderate CYP3A Inhibitors 
Antibiotics: ciprofloxacin, erythromycin 
Antifungals: fluconazole 
Protease inhibitors: amprenavir, atazanavir, darunavir, fosamprenavir 
Calcium channel blockers: diltiazem, verapamil 
Tyrosine kinase inhibitors (anticancer): imatinib 
Food products: grapefruit and juice (Citrus paradisi), Seville orange and juice (Citrus aurantium) 
Herbal medications: Schisandra sphenanthera 
Others: aprepitant, casopitant, cimetidine, cyclosporine, dronedarone, tofisopam 
Data compiled from the FDA’s “Guidance for Industry, Drug Interaction Studies;” 
http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm09
3664 htm  
 
from the Indiana University School of Medicine’s “Clinically Relevant” Table 
http://medicine.iupui.edu/flockhart/table.htm;  
 
from the University of Washington’s Drug Interaction Database  
www.druginteractioninfo.org 
 

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APPENDIX 13: MEDICATIONS TO BE USED WITH 
CAUTION (SENSITIVE CYP2C9 SUBSTRATES OR 
CYP2C9 SUBSTRATES WITH NARROW 
THERAPEUTIC INDEX) 
 
Celecoxib1 
Phenytoin2 
Warfarin2 
1 Sensitive substrates: Drugs that exhibit an AUC ratio (AUCi/AUC) of 5-fold or more when co-administered 
with a known potent inhibitor, where AUCi is the AUC of the substrate when coadministered with a known 
potent inhibitor and AUC is the AUC of substrate alone. 
2 Substrates with narrow therapeutic index (NTI): Drugs whose exposure-response indicates that increases in 
their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns (eg, 
Torsade de Pointes). 
 
 

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APPENDIX 14: MEDICATIONS TO BE USED WITH 
CAUTION (STRONG CYP2C8 INHIBITORS) 
 
Gemfibrozil 
 
 

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APPENDIX 15: PRE-EXISITING IMMUNE DEFICIENCIES 
OR AUTOIMMUNE DISEASES 
Prospective patients should be carefully questioned to determine whether they have any 
history of an acquired or congenital immune deficiency or autoimmune disease.  
Please contact the sponsor medical monitor regarding any uncertainty about immune 
deficiency/autoimmune disease exclusions.  
Acute disseminated encephalomyelitis 
Addison’s disease 
Ankylosing spondylitis 
Antiphospholipid antibody syndrome 
Aplastic anemia 
Autoimmune hemolytic anemia 
Autoimmune hepatitis 
Autoimmune hypoparathyroidism 
Autoimmune hypophysitis 
Autoimmune myocarditis 
Autoimmune oophoritis 
Autoimmune orchitis 
Autoimmune thrombocytopenic purpura 
Behcet’s disease 
Bullous pemphigoid 
Chronic inflammatory demyelinating 
polyneuropathy 
Chung-Strauss syndrome 
Crohn’s disease 
Dermatomyositis 
Dysautonomia  
Epidermolysis bullosa acquisita  
Gestational pemphigoid  
Giant cell arteritis  
Goodpasture’s syndrome  
Granulomatosis with polyangiitis  
Graves’ disease  
Guillain-Barré syndrome 
Hashimoto’s disease 
Immunoglobulin A (IgA) neuropathy 
Inflammatory bowel disease  
Interstitial cystitis  
Kawasaki’s disease  
Lambert-Eaton myasthenic syndrome 
Lupus erythematosus  
Lyme disease (chronic) 
Mooren’s ulcer  
Morphea  
Multiple sclerosis  
Myasthenia gravis 
Neuromyotonia  
Opsoclonus myoclonus syndrome  
Optic neuritis  
Ord’s thyroiditis  
Pemphigus  
Pernicious anemia  
Polyarteritis nodusa  
Polyarthritis  
Polyglandular autoimmune syndrome  
Primary biliary cirrhosis  
Psoriasis  
Reiter’s syndrome  
Rheumatoid arthritis  
Sarcoidosis  
Sjögren’s syndrome  
Stiff person syndrome 
Takayasu’s arteritis 
Ulcerative colitis 
Vogt-Kovangai-Harada disease 
 

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APPENDIX 16: NEW YORK HEART ASSOCIATION 
CLASSIFICATION 
 
NYHA 
Class 
Symptoms 
I 
Cardiac disease, but no symptoms and no limitation in ordinary physical activity, eg, no shortness 
of breath when walking, climbing stairs etc. 
II 
Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary 
activity. 
III 
Marked limitation in activity due to symptoms, even during less-than-ordinary activity, eg, 
walking short distances (20-100 m). Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. 
 

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APPENDIX 17: CONTRACEPTION GUIDELINES AND 
DEFINITIONS OF “WOMEN OF CHILDBEARING 
POTENTIAL”, “NO CHILDBEARING POTENTIAL” 
 
Contraception Guidelines 
The Clinical Trials Facilitation Group’s recommendations related to contraception and 
pregnancy testing in clinical trials include the use of highly effective forms of birth control. 
These methods include the following: 
 Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with the inhibition of ovulation (oral, intravaginal, or transdermal) 
o Progestogen-only hormonal contraception associated with the inhibition of ovulation 
(oral, injectable, or implantable) 
 Intrauterine device (IUD) 
 Intrauterine hormone-releasing system (IUS) 
 Bilateral tubal occlusion 
 Vasectomized male partner 
 Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of exposure associated with the study treatment). 
NOTE: Total sexual abstinence should only be used as a contraceptive method if it is in 
line with the patient’s usual and preferred lifestyle. Periodic abstinence (eg, calendar, 
ovulation, symptothermal, postovulation methods), declaration of abstinence for the 
duration of exposure to study drug, and withdrawal are not acceptable methods of 
contraception. 
Of note, barrier contraception (including male and female condoms with or without 
spermicide) is not considered a highly effective method of contraception and if used, this 
method must be combined with another acceptable method listed above. 
 
Definitions of “Women of Childbearing Potential,” “Women of No Childbearing Potential” 
As defined in this protocol, “women of childbearing potential” are female patients who are 
physiologically capable of becoming pregnant.  
Conversely, “women of no childbearing potential” are defined as female patients meeting 
any of the following criteria: 
 Surgically sterile (ie, through bilateral salpingectomy, bilateral oophorectomy, or 
hysterectomy) 
 Postmenopausal, defined as: 
o ≥ 55 years of age with no spontaneous menses for ≥ 12 months OR 
o < 55 years of age with no spontaneous menses for ≥ 12 months AND with 
postmenopausal follicle-stimulating hormone concentration > 30 IU/mL 
 

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Adapted from Clinical Trials Facilitation Group (CTFG).  Recommendations related to contraception and 
pregnancy testing in clinical trials.  September 15, 2014. 
http://www.hma.eu/fileadmin/dateien/Human Medicines/01-
About HMA/Working Groups/CTFG/2014 09 HMA CTFG Contraception.pdf 
 

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APPENDIX 18: CHRONIC KIDNEY DISEASE 
EPIDEMIOLOGY COLLABORATION EQUATION 
In adults, the most widely-used equations for estimating glomerular filtration rate (GFR) 
from serum creatinine are the Chronic Kidney Disease Epidemiology Collaboration (CKD-
EPI) equation and the Modification of Diet in Renal Disease (MDRD) Study equation. The 
National Kidney Disease Education Program (NKDEP) calculators rely on creatinine 
determinations which are isotope dilution mass spectrometry (IDMS) traceable.  All 
laboratories should be using creatinine methods calibrated to be IDMS traceable.  Read more 
about creatinine standardization. 
This CKD-EPI equation calculator should be used when SCr reported in mg/dL.  This 
equation is recommended when eGFR values above 60 mL/min/1.73 m2 are desired. 
The source of the equation shown below is as follows: 
 Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular 
filtration rate. Ann Intern Med. 2009;150(9):604-612. 
 
eGFR = 
141 × min(SCr/κ, 1)α × 
max(SCr /κ, 1)-1.209 × 
0.993Age × 
1.018 [if female] × 
1.159 [if Black] 
where: 
Scr is serum creatinine in mg/dL, 
κ is 0.7 for females and 0.9 for males, 
α is -0.329 for females and -0.411 for males, 
min indicates the minimum of SCr /κ or 1, and 
max indicates the maximum of SCr /κ or 1. 
Abbreviations: eGFR = estimated glomerular filtration rate; SCr = standardized serum creatinine; max 
= indicates the maximum of SCr/κ or 1min = indicates the minimum of SCr/κ or 1. 
 
The equation does not require weight because the results are reported normalized to 1.73 m2 
body surface area, which is an accepted average adult surface area. 
The online calculator for CKD-EPI can be found here:  
https://www.niddk.nih.gov/health-information/communication-programs/nkdep/laboratory-
evaluation/glomerular-filtration-rate-calculators