Clinical trial NCT02880371
Conditions: Advanced Solid Tumors
Keywords: Advanced Solid Tumors Pembrolizumab ARRY-382 CSF-1R CSF1R cfms
Sponsor: Pfizer
Start date: 2016-09-01; Completion date: 2019-10-24
Enrollment: 82 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is an open-label, multicenter Phase 1b/2 study to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ARRY-382 in combination with pembrolizumab in adult patients with selected advanced solid tumors (Part A/Phase 1b); and to estimate the efficacy of the combination in three separate cohorts: 1) patients with advanced solid tumors that have progressed on prior PD-1/PD-L1inhibitors, 2) patients with platinum-resistant ovarian cancer and 3) patients with pancreatic ductal adenocarcinoma (Phase 2).

Detailed description:
ARRY-382 is an inhibitor of CSF1R (colony-stimulating factor-1 receptor).

Each phase of the study consists of a 28-day screening period; 21-day treatment cycles with the combination of ARRY-382 and pembrolizumab until disease progression as determined by the Investigator, unacceptable toxicity, withdrawal of consent, or death (or other discontinuation criteria are met), and a 30-day safety follow-up period. Patients in all cohorts/phases will be monitored for overall survival (OS) until 1 year after the date of the last patient's first visit.

Arms: arm 1: Patients in Part A will receive escalating doses of single-agent ARRY-382 in combination with 2 mg/kg pembrolizumab. arm 2: Patients in Phase 2 will receive the MTD/RP2D dose of ARRY-382 determined during Part A in combination with 200mg pembrolizumab.
Interventions: intervention 1: ARRY-382 intervention 2: Pembrolizumab
Intervention descriptions: intervention 1: ARRAY-382 will be taken by mouth once daily at a fixed dose. intervention 2: Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.

Protocol documents:
Prot_000.pdf: 
ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
 
Version 4 
1 
Confidential 
24 July 2018 
 
 
Clinical Study ARRAY-382-201 
 
A Phase 1b/2 Study of ARRY-382 in Combination with Pembrolizumab,  
a Programmed Cell Death Receptor 1 (PD-1) Antibody, for the Treatment of  
Patients with Advanced Solid Tumors 
 
Protocol Version 1: 
Protocol Version 2: 
Protocol Version 3: 
Protocol Version 4:  
12 April 2016 
19 December 2016 
16 March 2018 
24 July 2018 
 
 
 
 
 
 
Array BioPharma Inc. 
 
3200 Walnut Street 
Boulder, CO 80301 
Phone: (303) 381-6600 
Fax: (303) 386-1240 
 
 
 
 
CONFIDENTIAL INFORMATION 
This document contains trade secrets and other confidential and proprietary information belonging to 
Array BioPharma Inc. Except as otherwise agreed to in writing, by accepting or reviewing this 
document you agree to hold this information in confidence and not to disclose it to others (except where 
required by applicable law) or to use it for unauthorized purposes. In the event of any actual or 
suspected breach of this obligation, Array BioPharma Inc. should be promptly notified. 


PPD


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
4 
Confidential 
24 July 2018 
PROTOCOL SYNOPSIS 
Title 
A Phase 1b/2 Study of ARRY-382 in Combination with 
Pembrolizumab, a Programmed Cell Death Receptor 1 (PD-1) 
Antibody, for the Treatment of Patients with Advanced Solid 
Tumors 
Protocol Number 
ARRAY-382-201 
Phase 
Phase 1b/2 
Study Center(s) 
Approximately 30 centers 
Objectives and 
Endpoints 
Phase 1b/Part A  
Primary objective: 
• To determine the maximum tolerated dose (MTD) and/or 
recommended Phase 2 dose (RP2D) of ARRY-382 in 
combination with pembrolizumab in patients with selected 
solid tumors 
Primary endpoint: 
• Incidence of dose-limiting toxicities (DLTs), as a function of 
the dose of ARRY-382 when administered in combination 
with pembrolizumab 
Secondary objectives: 
• To describe the preliminary antitumor activity of the 
combination based on the Response Criteria In Solid Tumors, 
version 1.1 (RECIST v1.1) 
• To describe the preliminary antitumor activity of the 
combination based on immune-related response criteria 
(irRC) 
• To characterize the safety and tolerability of the combination, 
including acute and chronic toxicities 
• To evaluate the pharmacokinetics (PK) of ARRY-382 in 
combination with pembrolizumab 
Secondary endpoints: 
• Objective response rate (ORR), as determined by the 
Investigator 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
12 
Confidential 
24 July 2018 
QD. If a Grade 3 immune-related adverse event (irAE) (first 
occurrence) is reported in a given cohort, enrollment in that cohort 
will continue at the same dose until the toxicity is evaluated. If a 
second Grade 3 irAE is reported or a first Grade 3 irAE is reported in 
addition to a previous DLT in a given cohort, enrollment of new 
patients in that cohort will be stopped until the Grade 3 irAE is 
evaluated. If the event is not a DLT (as determined by the 
Investigators in consultation with the Sponsor), then enrollment may 
be resumed, or the cohort may be expanded to include up to 
9 patients. If the Grade 3 irAE is deemed a DLT, the MTD has been 
achieved and additional patients will be enrolled at the previous dose 
level or at an intermediate dose level. 
Intermediate doses and doses higher than 400 mg QD may also be 
considered upon review of the safety and PK results from the planned 
dose cohorts. In the absence of identification of an MTD, a dose of 
400 mg or lower may be selected as the RP2D as long as the DLT 
rate is < 33% (e.g., fewer than 2 of 6 patients experience a DLT). 
Part A has been completed and the MTD/RP2D of ARRY-382 was 
determined to be 300 mg QD in combination with pembrolizumab.  
Phase 2 will consist of 3 separate cohorts of patients. The Phase 2 
PD-1/PD-L1 Inhibitor Refractory cohort will consist of patients with 
advanced solid tumors who progressed on a PD-1/PD-L1 
inhibitor-containing regimen as their most recent prior line of therapy 
are who are naïve to prior CSF-1R or CSF-1 inhibitors. The Phase 2 
prOVCA and PDA cohorts will consist of patients with prOVCA and 
patients with PDA, respectively, who have had at least one prior line 
of therapy and who are naïve to prior checkpoint inhibitor (CPI) 
therapy and to prior CSF-1R or CSF-1 inhibitors.  
In Phase 2, at baseline, submission of archived tumor tissue from the 
most recent sample collection available or a fresh biopsy will be 
required.  
All patients in Phase 2 will receive ARRY-382 at 300 mg QD, the 
MTD/RP2D determined during Part A, in combination with 
pembrolizumab 200 mg iv Q3W. 
Efficacy assessments include determination of objective response 
using RECIST v1.1. For patients who have initial evidence of 
radiological progressive disease (PD) by RECIST v1.1, it will be at 
the discretion of the Investigator to keep a patient on study treatment 
or to stop study treatment until repeat imaging is performed 
approximately 4 weeks later in order to confirm PD per irRC. 
Patients with confirmed irPD should discontinue treatment. Patients 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
14 
Confidential 
24 July 2018 
carcinoma (HNSCC), bladder cancer, metastatic colorectal cancer 
(CRC), PDA, or gastric cancer. Patients who had prior treatment with 
an immune CPI (e.g., programmed cell death receptor 1 [PD-1], PD-
L1, or cytotoxic T-lymphocyte antigen 4 [CTLA-4] inhibitor) will be 
excluded. Prior treatment with ipilimumab administered as adjuvant 
therapy in patients with melanoma is allowed. Prior treatment with a 
CSF-1R or CSF-1 (or macrophage colony-stimulating factor 
[MCSF]) inhibitor is allowed. 
The Phase 2 PD-1/PD-L1 Inhibitor Refractory cohort will consist of 
up to 20 patients with advanced solid tumors who progressed on a 
PD-1/PD-L1 inhibitor-containing regimen as their most recent prior 
line of therapy. If clinical activity is observed, enrollment may be 
focused to include up to 10 additional patients with particular tumor 
histologies of interest.   
The Phase 2 prOVCA cohort will consist of approximately 
23 patients with prOVCA who are naïve to prior CPI therapy. The 
Phase 2 PDA cohort will consist of approximately 29 patients with 
PDA who have had at least one prior therapy who are naïve to prior 
CPI therapy. 
Duration of Study 
Participation 
Each phase of the study consists of a 28-day screening period; 21-day 
treatment cycles with the combination of ARRY-382 and 
pembrolizumab until disease progression as determined by the 
Investigator, unacceptable toxicity, withdrawal of consent, or death 
(or other discontinuation criteria are met); and a 30-day safety 
follow-up period.  
Patients will be monitored for OS until 1 year after the date of the last 
patient’s first visit. 
Statistical 
Considerations 
For Part A, the sample size of approximately 18 evaluable patients 
(i.e., 6 to 9 patients in each dose cohort) is standard for purposes of 
determining the MTD and RP2D. Patients will be considered 
evaluable if they complete Cycle 1 or discontinue treatment due to 
DLT during Cycle 1. 
For the Phase 2 PD-1/PD-L1 Inhibitor Refractory cohort, the sample 
size of up to 20 patients will be evaluated for initial evidence of 
activity in this PD-1/PD-L1 inhibitor-refractory population.  
For the Phase 2 prOVCA cohort, a Simon’s 2-stage optimal design 
will be used in the MSS/MMR-proficient prOVCA population. The 
null hypothesis of the true response rate is 15%, versus alternative of 
35%. Accrual of patients in Stage 1 will continue until 9 evaluable 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
15 
Confidential 
24 July 2018 
MSS/MMR-proficient patients have been enrolled, with evaluable 
defined as having received at least one dose of study drug. The 
analysis for Stage 1 will not occur until all evaluable patients in Stage 
1 have had the opportunity to have at least 2 post-baseline tumor 
assessments (or have discontinued tumor assessments beforehand). If 
there are less than 2 responders in these 9 patients, enrollment into 
this cohort of the study will be stopped. Otherwise, 14 additional 
patients will be accrued during Stage 2, for a total of 23 patients 
enrolled in this cohort. The null hypothesis will be rejected if 6 or 
more responses are observed in 23 patients. With this sample size, the 
actual Type I error is 9.9%, and the power is 80%. If the null 
hypothesis is true, the expected sample size is 15 patients, and the 
probability of stopping enrollment into this cohort of the study early 
is 60%. Patients who are MSI-H/mismatch repair-deficient (dMMR) 
will not be included in the Simon’s 2-stage analyses and the study 
will ensure that the sample size requirements are met by enrolling the 
required number of MSS/MMR-proficient prOVCA patients. 
For the Phase 2 PDA cohort, a Simon’s 2-stage optimal design will 
be used in the MSS/MMR-proficient PDA population. The null 
hypothesis of the true response rate is 4%, versus alternative of 15%. 
Accrual of patients in Stage 1 will continue until 15 evaluable 
MSS/MMR-proficient patients have been enrolled, with evaluable 
defined as having received at least one dose of study drug. The 
analysis for Stage 1 will not occur until all evaluable patients in Stage 
1 have had the opportunity to have at least 2 post-baseline tumor 
assessments (or have discontinued tumor assessments beforehand). If 
there are no responders in these 15 patients, enrollment into this 
cohort of the study will be stopped. Otherwise, 14 additional 
MSS/MMR-proficient patients will be accrued during Stage 2, for a 
total of 29 patients enrolled in this cohort. The null hypothesis will be 
rejected if 3 or more responses are observed in 29 MSS/MMR-
proficient patients. With this sample size, the actual Type I error is 
9.9%, and the power is 80%. If the null hypothesis is true, the 
expected sample size is 21 patients, and the probability of stopping 
enrollment into this cohort of the study early is 54%. PDA patients 
who are MSI-H/dMMR will not be included in the Simon’s 2-stage 
analyses and the study will ensure that the sample size requirements 
are met by enrolling the required number of MSS/MMR-proficient 
PDA patients. 
Objective response rate and 95% confidence intervals (CIs) will be 
reported. For time-to-event variables (i.e., DOR, PFS, OS), the 
survival distribution functions will be estimated using the Kaplan-


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A R R Y -3 8 2  (C S F -1 R i n hi bit or)  
Arra y Bi o P har ma I nc.  
Cli nical St u d y A R R A Y -3 8 2 -2 0 1  
 
Versi o n 4  
1 7  
C o nfi de ntial  
2 4 J ul y  2 0 1 8  
T A B L E O F C O N T E N T S  
1. 0  I N V E S TI G A T O R S A N D S T U D Y A D MI NI S T R A TI V E ST R U C T U R E  .................. 4 8 
2. 0  I N T R O D U C TI O N ......................................................................................................... 4 9 
2. 1  
Bac k gr o u n d T hera p e utic I nf or mati o n  ....................................................................... 4 9 
2. 1. 1  
P D - 1 a n d P D - L 1 I n hi bit or Resista nce ............................................................... 5 0 
2. 1. 2  
Mali g na nt Mel a n o ma  ......................................................................................... 5 0 
2. 1. 3  
N o n -S mall Cell L u n g Car ci n o ma ...................................................................... 5 1  
2. 1. 4  
O varia n Ca n cer  .................................................................................................. 5 2 
2. 1. 5  
Pa ncreatic C a ncer  .............................................................................................. 5 2 
2. 2  
I n v esti gati o nal Me dici nal Pr o d uct ............................................................................ 5 3 
2. 2. 1  
N o ncli nical St u dies wit h A R R Y - 3 8 2 ................................................................. 5 3 
2. 2. 2  
Cli nical E x perie nce wit h A R R Y - 3 8 2 ( Cli nical St u d y A R R A Y- 3 8 2- 1 0 1) ......... 5 5 
2. 3  
Rati o nale f or t he C urr e nt St u d y ................................................................................ 5 9  
2. 3. 1  
P hase 1 b ( Part A)  ............................................................................................... 5 9 
2. 3. 2  
P hase 2  ............................................................................................................... 6 0 
2. 4  
D ose Selecti o n  .......................................................................................................... 6 1 
3. 0  S T U D Y O B J E C TI V E S A N D  E N D P OI N T S  ................................................................ 6 2 
3. 1  
P hase 1 b ( Part A)  ...................................................................................................... 6 2 
3. 2  
P hase 2  ...................................................................................................................... 6 3 
4. 0  S T U D Y D E SI G N  ........................................................................................................... 6 7 
4. 1  
St u d y Desi g n O ver vie w ............................................................................................ 6 7  
4. 2  
D ose -Li miti n g To xicities ( Part A)  ............................................................................. 6 9 
4. 3  
E n d of St u d y ............................................................................................................. 7 1  
5. 0  P A TI E N T P O P U L A TI O N  ............................................................................................. 7 2 
5. 1  
N u m ber of Patie nts ................................................................................................... 7 2  
5. 2  
Selecti o n of Patie nts  .................................................................................................. 7 2 
5. 2. 1  
I n cl usi o n Criteria ............................................................................................... 7 2 
5. 2. 2  
E x cl usi o n Criteria  .............................................................................................. 7 5 
5. 3  
C o ntrace pti o n ............................................................................................................ 7 7  
6. 0  S T U D Y T R E A T M E N T A N D C O N C O MI T A N T M E DI C A TI O N S  .......................... 7 9 
6. 1  
S t u d y Tr eat me nt S u p plies ......................................................................................... 7 9 
6. 1. 1  
Ma n ufact uri n g a n d F or m ulati o n ........................................................................ 7 9  
6. 1. 2  
Pac ka gi n g a n d La b eli n g  ..................................................................................... 7 9 
6. 1. 3  
S hi p pi n g, St ora ge a n d H a n dli n g ........................................................................ 8 0  
6. 1. 4  
Acc o u nta bilit y a n d Ret ur n of St u d y Dr u g S u p pl y............................................. 8 0  
6. 2  
St u d y Dr u g Dis pe nsi n g a n d A d mi nistrati o n  ............................................................. 8 0 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
20 
Confidential 
24 July 2018 
13.0 REGULATORY, ETHICAL AND LEGAL OBLIGATIONS .................................. 127 
13.1 
Good Clinical Practice ............................................................................................ 127 
13.2 
Ethics Committee Approval .................................................................................... 127 
13.3 
Regulatory Authority Approval ............................................................................... 127 
13.4 
Other Required Approvals ...................................................................................... 127 
13.5 
Informed Consent.................................................................................................... 127 
13.6 
Patient Confidentiality ............................................................................................ 128 
13.7 
Disclosure of Information ....................................................................................... 128 
13.8 
Publication of Study Data ....................................................................................... 128 
14.0 ADHERENCE TO THE PROTOCOL ...................................................................... 129 
14.1 
Amendments to the Protocol ................................................................................... 129 
15.0 REFERENCES ............................................................................................................ 130 
 
 


A R R Y -3 8 2  (C S F -1 R i n hi bit or)  
Arra y Bi o P har ma I nc.  
Cli nical St u d y A R R A Y -3 8 2 -2 0 1  
 
Versi o n 4  
2 1  
C o nfi de ntial  
2 4 J ul y  2 0 1 8  
LI S T O F T A B L E S  
Ta ble  1: 
All A d verse E v e nts Re p orte d i n ≥ 1 5 % of All Patie nts ( Cli nical 
St u d y A R R A Y - 3 8 2- 1 0 1) ...................................................................................... 5 6 
Ta ble  2: 
O bjecti ves a n d E n d p oi nts ( P hase 1 b/ Part A) ....................................................... 6 2  
Ta ble  3: 
O bjecti ves a n d E n d p oi nts ( P hase 2: P D - 1 or P D- L 1 I n hi bit or Refract or y) ......... 6 4 
Ta ble  4: 
O bjecti ves a n d E n d p oi nts ( P hase 2: pr O V C A) .................................................... 6 5  
Ta ble  5: 
O bjecti ves a n d E n d p oi nts ( P hase 2: P D A) ........................................................... 6 6  
Ta ble  6: 
Pla n ne d D ose C o h orts ( Part A) ............................................................................ 6 8  
Ta ble  7: 
D ose -Li miti n g T o xicities ( Part A)  ....................................................................... 7 0 
Ta ble  8: 
Rec o m me n de d D ose M o dificati o ns f or A R R Y- 3 8 2 Treat me nt -Relat e d A d v erse 
E ve nts ................................................................................................................... 8 3  
Ta ble  9: 
Cli nical La b or at or y Tests  ..................................................................................... 9 2 
Ta ble  1 0: 
Sc he d ule of E ve nts ( Part A/ P hase 1 b) ................................................................ 1 0 7  
Ta ble  1 1: 
Sc he d ule of E ve nts ( P has e 2) ............................................................................. 1 1 0  
Ta ble  1 2: 
Bi n o mial Pr o ba bilities of D ose -Li miti n g T o xicit y i n a C o h ort of 6 Patie nts  .... 1 2 0 
Ta ble  1 3: 
Bi n o mial Pr o ba bilities of D ose -Li miti n g T o xicit y i n a C o h ort of 9 Patie nts  .... 1 2 1 
 
L I S T O F A P P E N DI C E S 
A p pe n di x 1 Easter n C o o perati ve O n c ol o g y Gr o u p Perf or ma nce Stat us ............................... 1 3 5  
A p pe n di x 2 Dr u gs wit h Ris k of T D P/ P ote ntial t o Pr ol o n g Q T I nt er val a n d C Y P 3 A 
I n hi bit ors/I n d ucers .............................................................................................. 1 3 6 
A p pe n di x 3 C hil d P u g h Classificati o n  ................................................................................... 1 3 7 
A p pe n di x 4 C o nc o mita nt Me dicati o ns t o Be Us e d wit h Ca uti o n .......................................... 1 3 8  
A p pe n di x 5 Res p o nse Criteria i n S oli d T u m ors, Versi o n 1. 1................................................ 1 4 0  
A p pe n di x 6 I m m u ne - Rel ate d Res p o nse Criteria i n S oli d T u m ors ........................................ 1 4 6 
 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
22 
Confidential 
24 July 2018 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
The following abbreviations and special terms are used in this study protocol. 
Abbreviation or  
special term 
Explanation 
AE 
adverse event 
ALK 
anaplastic lymphoma kinase 
ALT  
alanine aminotransferase  
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST  
aspartate aminotransferase  
AUC 
area under the plasma concentration-time curve 
AUCτ 
area under the plasma concentration-time curve over the dosing interval 
BCE 
bone collagen equivalents 
BUN 
blood urea nitrogen 
CA-125 
cancer antigen 125 
CA 19-9 
cancer antigen 19-9 
cFMS 
cellular homolog of the V-FMS oncogene product of the Susan McDonough strain of feline 
sarcoma virus, also known as colony-stimulating factor 1 receptor (CSF-1R) 
CI 
confidence interval 
CK 
creatine kinase 
Cmax 
maximum observed plasma concentration 
CNS 
central nervous system 
CPI 
checkpoint inhibitor 
CR 
complete response 
CRC 
colorectal cancer 
CRO 
contract research organization 
CSF-1 
colony-stimulating factor 1 
CSF-1R 
colony-stimulating factor 1 receptor 
CT 
computed tomography 
CTC 
circulating tumor cell 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte antigen 4 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
24 
Confidential 
24 July 2018 
Abbreviation or  
special term 
Explanation 
IC50 
concentration required for 50% inhibition 
ICH 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use 
IL 
interleukin 
INR 
international normalized ratio 
irAE 
immune-related adverse event 
IRB 
Institutional Review Board 
irBOR 
immune-related best overall response 
irCR 
immune-related complete response 
irPD 
immune-related progressive disease 
irPFS 
immune-related progression-free survival 
irPR 
immune-related partial response 
irRC 
immune-related response criteria 
irRR 
immune-related response rate 
irSD 
immune-related stable disease 
ISH 
International Society of Hypertension 
iv 
intravenously 
k 
number of dose-limiting toxicities 
LLC-PK1 
pig kidney epithelial cell line 
mAb 
monoclonal antibody 
MCP-1 
monocyte chemoattractant protein 1 
MCSF 
macrophage colony-stimulating factor 
MDSC 
myeloid-derived suppressor cell 
MedDRA 
Medical Dictionary for Regulatory Affairs 
MIP-1b 
macrophage inflammatory protein 1 beta 
MMR 
mismatch repair 
Mo-MDSC 
monocytic myeloid-derived suppressor cell 
MRI 
magnetic resonance imaging 
MSI 
microsatellite instability 
MSI-H 
microsatellite instability-high  
MSS 
microsatellite stable 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
 
Version 4 
27 
Confidential 
24 July 2018 
SUMMARY OF CHANGES FOR PROTOCOL VERSION 4 
Rationale: 
At the time of this protocol amendment, the study had been initiated at 11 study centers, 
31 patients have been treated (19 in Part A, 1 melanoma patient in previous Part B, 2 NSCLC in 
previous Part C and 9 in Phase 2) and enrollment in Part A has been completed. 
The rationale for the key changes to the protocol includes: 
• Detailed information regarding dose modification and discontinuation of pembrolizumab 
was removed and, as the prescribing information for pembrolizumab varies across 
countries, sites are instructed to follow the most current local Prescribing Information for 
dose modification guidelines. In addition, information on a pembrolizumab formulation 
now available in the European Union (EU) was added. Furthermore, it was clarified that 
pembrolizumab will be administered at 200 mg in Phase 2. 
• Rationale: To account for the changes in pembrolizumab formulation and the 
rapidly evolving changes in pembrolizumab indication and administration and for 
clarity. 
• A correction was made to add mismatch repair (MMR) proficiency in places where 
microsatellite instability (MSI) status was noted.  
• Rationale: To be consistent with the study sample and the statistical 
considerations. 
Changes to the Protocol: 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strikethrough font for deletions and underlined font for insertions. 
Abbreviations have been updated throughout to account for changes to the protocol and are not 
otherwise noted in section changes below. 
Summary of Changes for Protocol Version 4:  
Section added to discuss this amendment. 
Protocol Synopsis:  
Section was updated to match the body of the protocol. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
28 
Confidential 
24 July 2018 
Section 2.4 Dose Selection 
Section was modified to remove “according to the Prescribing Information for Keytruda® 
(pembrolizumab)” in the Phase 2 instructions for pembrolizumab administration. 
Section 6.1.1 Manufacturing and Formulation 
Section was updated to provide information on the 2 currently available pembrolizumab 
formulations in the European Union. 
Section 6.1.2 Packaging and Labeling 
Section was updated to state that the Sponsor, or designee, will provide each site with the most 
current local pembrolizumab Prescribing Information and distribute any updates as they become 
available. 
Section 6.2.2 Pembrolizumab 
Section was modified to remove “as instructed on the local label” in the Phase 2 instructions for 
pembrolizumab administration. 
Section 6.3.3 Pembrolizumab 
Section was modified to remove details regarding dose modification and discontinuation of 
pembrolizumab and instead added instructions to follow the current locally approved Prescribing 
Information. 
Section 6.5.3 Prohibited Medications 
Section was updated to add instructions to consult the most current local pembrolizumab 
Prescribing Information for any additional prohibited medications.   
Section 7.1.1 Medical History/Disease History 
Section was updated with administrative changes/corrections regarding the study population.   
Section 7.1.5 Tumor and Blood Samples for Retrospective Testing of Tumor Genomic 
Alterations, Tumor Mutation Burden and/or Gene Expression Profiling (Phase 2 Only) 
Section was updated with administrative changes/corrections regarding the study population. 
Section 7.5.2 Clinical Laboratory Tests 
Section/Table 9 was updated to allow for urine myoglobin to only be collected if blood CK 
levels are elevated. 
Section 8.1 Screening Evaluations 
Section was updated with administrative changes/corrections regarding the study population. 
Section 9.3 Replacement of Patients 
Section was updated with administrative changes/corrections regarding the study population. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
29 
Confidential 
24 July 2018 
Section 11.1.1 Sample Size 
Section was updated with administrative changes/corrections regarding the study population. 
Section 15.0 References 
Section updated with new references to reflect changes to protocol content. 
Appendices 
Previous Appendix 4 (Immune-Related Adverse Reactions Associated with Pembrolizumab) was 
removed and previous Appendices 5, 6, 7 were renumbered to Appendices 4, 5, 6, respectively. 
 
 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
30 
Confidential 
24 July 2018 
SUMMARY OF CHANGES FOR PROTOCOL VERSION 3 
Rationale: 
At the time of this protocol amendment, the study had been initiated at 11 study centers, 
21 patients have been treated (19 in Part A, 1 melanoma patient in previous Part B and 1 NSCLC 
in previous Part C) and enrollment in Part A has been completed. 
The rationale for the key changes to the protocol includes: 
• The Phase 1b Expansion cohort in melanoma patients (Part B) and the Phase 2 cohort in non-
small cell lung cancer (NSCLC) patients (Part C) have been removed and replaced with 
3 new Phase 2 cohorts in programmed cell death receptor 1 (PD-1)/programmed cell death 
ligand 1 (PD-L1) inhibitor-refractory patients, platinum-resistant ovarian cancer (prOVCA) 
patients and pancreatic ductal adenocarcinoma (PDA) patients. As such, specific 
objectives/endpoints, background information and rationale, inclusion/exclusion criteria, 
assessments and statistical methods were added for each cohort in Phase 2 and sections and 
content pertaining specifically to previous Parts B and C have been removed. 
• Rationale: Preclinical data in the literature suggests that activated macrophages may 
represent one potential mechanism of PD-1/PD-L1 inhibitor resistance. Thus, there is 
the potential that the addition of a colony-stimulating factor 1 receptor (CSF-1R) 
inhibitor to a patient with progression on a prior PD-1/PD-L1 inhibitor-containing 
regimen may result in clinical activity. Phase 2 indications were modified as a result 
of clinical evidence of activity with combined PD-1 and CSF-1R inhibition in patients 
with advanced PDA and initial evidence of activity seen in Part A of this study in 
patients with PDA and ovarian cancer. Another consideration for changing the 
Phase 2 indications was the changing clinical landscape regarding the use of PD-1 
inhibitors in the treatment of patients with NSCLC.   
• To modify the dose of pembrolizumab to be used in combination with ARRY-382 in Phase 2 
from 2 mg/kg to a flat dose of 200 mg intravenously (iv) every 3 weeks (Q3W). 
• Rationale: To conform to the current pembrolizumab label. 
• To update the number of study centers from approximately 10 to approximately 30. 
• Rationale: To account for the additional patients planned to be enrolled in Phase 2. 
• To modify the overall sample size from approximately 71 patients to approximately 
90 patients. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
31 
Confidential 
24 July 2018 
• Rationale: To account for the additional patients planned to be enrolled in Phase 2. 
• To clarify that, with the exception of Cycle 1, the pembrolizumab dose does not have to 
occur on Day 1 of each cycle. 
• Rationale: To clarify that administration of either ARRY-382 or pembrolizumab will 
define the re-start of subsequent cycles following temporary dosing hold. 
• To clarify that patients may remain on study treatment until the confirmation of disease 
progression by the Investigator per immune-related response criteria (irRC). 
• Rationale: To allow study treatment beyond initial progressive disease (PD) per 
Response Criteria in Solid Tumors, version 1.1 (RECIST v1.1) criteria to align with 
irRC criteria for establishing disease progression.  
• To clarify that tumor assessments should be performed once every 6 weeks (± 7 days), 
regardless of treatment interruptions. 
• Rationale: To ensure that tumor assessments are performed at consistent time 
intervals in all patients and not based on treatment cycles which may be of varying 
durations due to patient tolerability. 
• To add that all data acquired for efficacy purposes obtained at Screening and while on study, 
including any off-schedule imaging studies performed, should be made available if requested 
by the Sponsor for central assessment by an independent reviewer. 
• Rationale: To allow for independent confirmation of the tumor assessment data if it is 
required to better understand the observed activity in the trial. 
• To clarify that the Treatment Discontinuation Visit and the 30-Day Safety Follow-up Visit 
should occur as specified or prior to the initiation of subsequent anticancer therapy, 
whichever occurs first. 
• Rationale: To conduct these visits prior to the initiation of subsequent anticancer 
therapy. 
• To add that any subsequent anticancer therapies should be recorded throughout the survival 
follow-up period. 
• Rationale: To collect this information as these treatments can impact overall survival 
(OS). 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
32 
Confidential 
24 July 2018 
• To add ARRY-382 dose modifications for hepatic enzyme elevations. 
• Rationale: To provide more specific dose modifications for elevations of hepatic 
enzyme based on time to resolution in order ensure that the patients receive the 
adequate dose that is safe. 
• To update the pembrolizumab dose modification information based on updated data and to 
clarify that modification should be based on the most recent, local pembrolizumab label. 
• Rationale: To provide the latest information on dose modification based on recent 
label updates and to note that the most current local label should be referenced in the 
future.   
• To modify predose blood collections for PK from within 60 minutes to within 120 minutes 
prior to administration of ARRY-382. 
• Rationale: Broadens the collection window for ease of sample collection without 
significantly impacting the quality of the PK data. 
• To modify hepatitis testing such that hepatitis C virus (HCV) ribonucleic acid (RNA) 
qualitative will be required only if HCV serology is positive. 
• Rationale: To avoid unnecessary additional testing in patients. 
• To clarify that direct bilirubin only needs to be collected when total bilirubin values are 
above normal. 
• Rationale: Any increase in direct bilirubin will be reflected in the total bilirubin 
levels. Thus, if the total bilirubin is not elevated, evaluation of the direct bilirubin 
levels is not necessary. 
• To clarify that creatine kinase (CK) isoenzymes only need to be collected when total CK is 
≥ Grade 2; unless there are cardiac signs and symptoms. 
• Rationale: To avoid unnecessary additional testing in patients with mild, 
asymptomatic CK elevations. 
• To permit the substitution of a telephone call for the Day 15 clinic visit of Cycles ≥ 5. 
• Rationale: To improve patient convenience while still requiring oversight by the site. 
• To update protocol instructions regarding documentation of adverse events (AEs). 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
33 
Confidential 
24 July 2018 
• Rationale: To align with current Sponsor language. 
• Other (clarifications and corrections). 
Changes to the Protocol: 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strikethrough font for deletions and underlined font for insertions. 
Abbreviations have been updated throughout to account for changes to the protocol and are not 
otherwise noted in section changes below. 
References have been modified from a numbered format to an alphabetical format and are not 
otherwise noted in section changes below. 
Summary of Changes for Protocol Version 3:  
Section added to discuss this amendment. 
Protocol Synopsis:  
Section has been updated to match the body of the protocol. 
Section 2.1.1 PD-1 and PD-L1 Inhibitor Resistance: 
Section added to provide background information for the PD-1/PD-L1 inhibitor refractory 
population. 
Section 2.1.3 Non-Small Cell Lung Carcinoma:  
Section modified to provide additional details of pembrolizumab treatment in patients with 
NSCLC. 
Section 2.1.4 Ovarian Cancer: 
Section added to include background information for the ovarian cancer population and literature 
results of treatment of these patients. 
Section 2.1.5 Pancreatic Cancer:  
Section added to provide background information for the pancreatic cancer population and 
literature results of treatment of these patients. 
Section 2.2.2 Clinical Experience with ARRY-382 (Clinical Study ARRAY-382-101): 
Section title updated with administrative changes/corrections. 
Section 2.2.2.1 Clinical Safety:  
Section modified to provide a mechanistic rationale for observed hepatic enzyme elevations and 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
34 
Confidential 
24 July 2018 
Table 1 (All Adverse Events Reported in ≥ 15% of All Patients [Clinical Study ARRAY-382-
101]) updated with administrative changes/corrections. 
Section 2.2.2.2 Clinical Pharmacokinetics:  
Section updated with administrative changes/corrections. 
Section 2.3 Rationale for the Current Study:  
Section updated with administrative changes/corrections. 
Section 2.3.1 Phase 1b (Part A):  
Section updated with results from Part A. 
Section updated with administrative changes. 
Previous Section 2.3.2 Phase 1b Expansion (Part B): 
Section deleted as it is no longer applicable.  
Section 2.3.2 Phase 2: 
Section title and section text modified to provide the rationale for the new patient populations in 
Phase 2 (PD-1/PD-L1 inhibitor refractory patients, prOVCA patients and PDA patients) and to 
remove information pertaining specifically to previous Part C. 
Section 2.4 Dose Selection:  
Section modified to clarify the dosing and administration information for ARRY-382 and 
pembrolizumab in Phase 2 and to include the MTD/RP2D for ARRY-382 of 300 mg QD, 
determined during Part A which will be used in the Phase 2 cohorts. 
Previous Section 3.2 Phase 1b Expansion (Part B): 
Section and previous Table 3 deleted as no longer applicable. 
Section 3.2 Phase 2:  
Section header modified, previous Table 4 deleted and Table 3 (Objectives and Endpoints 
[Phase 2: PD-1 or PD-L1 Inhibitor Refractory]), Table 4 (Objectives and Endpoints [Phase 2: 
prOVCA]) and Table 5 (Objectives and Endpoints [Phase 2: PDA]) added to account for the new 
objectives and endpoints for each of the 3 Phase 2 cohorts noted above.  
Section 4.1 Study Design Overview:  
Section modified to account for changes/additions to study design for each of the Phase 2 cohorts 
of the study.  
Section modified to include the MTD/RP2D for ARRY-382 of 300 mg QD, determined during 
Part A, which will be used in the Phase 2 cohorts. 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
36 
Confidential 
24 July 2018 
Exclusion criteria #9, pertaining to patients with symptomatic ascites or symptomatic pleural 
effusion, was modified for clarity and to add a consideration for the prOVCA patients. 
Exclusion criteria #18, pertaining to prior therapy, was modified for clarity. 
Exclusion criteria #19, pertaining to residual Common Terminology Criteria for Adverse Events 
(CTCAE) ≥ Grade 2 side effects of any prior therapy, was modified for clarity. 
Exclusion criteria #21, pertaining to hepatitis B and C testing, was modified such that HCV RNA 
qualitative will be required only if HCV serology is positive. 
Section 5.3 Contraception: 
Section added to define contraception requirements for patients. 
Section 6.1.1 Manufacturing and Formulation: 
Section updated to clarify the manufacturer of ARRY-382 capsules and added details about 
market authorization holder for pembrolizumab in the European Union (EU) and specified 
formulation that is available in the EU. 
Section 6.1.2 Packaging and Labeling: 
Section modified to update the packaging and labeling details for ARRY-382 and 
pembrolizumab. 
Section 6.1.3 Shipping, Storage and Handling: 
Section updated with administrative changes/corrections. 
Previous Section 6.2.1.2 Part B: 
Section deleted as no longer applicable. 
Section 6.2.1.2 Phase 2: 
Title and section updated to account for the changes to Phase 2. 
Section 6.2.2 Pembrolizumab: 
Section modified to modify/add pembrolizumab administration details for Phase 2. 
Section 6.3 Dose Modifications and Reductions: 
Section updated to clarify that Cycle 1 Day 1 is defined as the first day of study drug treatment 
with both ARRY-382 and pembrolizumab and administration of either ARRY-382 or 
pembrolizumab will define the re-start of subsequent cycles following temporary dosing hold. 
Section 6.3.1 General Guidelines: 
Section updated with administrative changes/corrections. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
37 
Confidential 
24 July 2018 
Section 6.3.2 ARRY-382: 
Table 8 (Recommended Dose Modifications for ARRY-382 
Treatment-Related Adverse Events) updated to add ARRY-382 dose 
modifications for hepatic enzyme elevations and to modify footnote “a” 
pertaining to increased CK.  
Section modified to account for the different phases of the study and to clarify that ARRY-382 
dose reductions should occur in 100 mg increments.  
Text pertaining to dose reductions in Parts B and C with a possible starting dose of ≥ 400 mg 
was removed as no longer applicable. 
Section 6.3.3 Pembrolizumab: 
Section updated to state that pembrolizumab should be withheld or discontinued for any of the 
specified toxicities listed in the most current, local label unless they are considered to be clearly 
attributable to ARRY-382, concurrent illness, or underlying disease. Additional toxicities were 
added for consideration of dose modification or discontinuation, per the most current label.  
Section updated with other administrative changes/corrections. 
Section 7.1.1 Medical History/Disease History: 
Section title and section text updated to include collection of disease history information. 
Section 7.1.3 Hepatitis Tests: 
Section title was changed for clarity and section text was modified such that HCV RNA 
qualitative will be required only if HCV serology is positive. 
Section 7.1.4. Local and Retrospective Testing for PD-L1 Expression (Part A Patients with 
Non-Small Cell Lung Carcinoma Only): 
Section updated to remove reference to Part C as no longer applicable. 
Section 7.1.5 Tumor and Blood Samples for Retrospective Testing of Tumor Genomic 
Alterations, Tumor Mutation Burden and/or Gene Expression Profiling (Phase 2 Only): 
Section added to state that in Phase 2, patients must have a fresh biopsy (preferred) or an archival 
tumor sample from the most recent sample available submitted to be eligible for participation in 
the study and to provide instructions for obtaining PD-L1 expression, tumor genomic alterations 
including microsatellite instability (MSI) status, tumor mutation burden and/or gene expression 
profiling status. 
Section 7.2 Efficacy Assessments: 
Section modified to clarify that patients may remain on study treatment until the confirmation of 
disease progression by the Investigator per irRC and to add that all data acquired for efficacy 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
38 
Confidential 
24 July 2018 
purposes should be made available if requested by the Sponsor for central assessment by an 
independent reviewer. 
Section 7.2.2 Immune-Related Response Criteria: 
Section updated with administrative changes/corrections. 
Previous Section 7.3.1 Macrophages, T Cells, and Other Immune Markers in Tumor 
Tissue: 
Section deleted as no longer applicable.  
Section 7.3.1.1 Markers of CSF-1R Inhibition: 
Section updated with administrative changes/corrections and to include the measurement of 
NCM in peripheral blood in Phase 2. 
Section 7.3.1.3 Tumor Markers (Phase 2 Only): 
Section added to include details regarding measurement of tumor markers. 
Section 7.4 Pharmacokinetic Assessments: 
Section modified to clarify that pembrolizumab concentrations are not planned to be measured 
but that remaining PK plasma samples may be used to assess pembrolizumab concentrations on 
an ad hoc basis.  
Section modified to move predose blood collections for PK from within 60 minutes to within 
120 minutes prior to administration of ARRY-382. 
Section updated with administrative changes/corrections. 
Section 7.5.1 Adverse Events: 
Section updated to include reference to Table 10 (Schedule of Events [Part A/Phase 1b]) and 
Table 11 (Schedule of Events [Phase 2]). 
Section 7.5.2 Clinical Laboratory Tests: 
Table 9 (Clinical Laboratory Tests) updated to clarify that direct bilirubin will only be collected 
when total bilirubin values are above normal. 
Table 9 (Clinical Laboratory Tests) updated to clarify that CK isoenzymes will only be collected 
when total CK is ≥ Grade 2, unless there are cardiac signs and symptoms. 
Table 9 (Clinical Laboratory Tests) was modified such that HCV RNA qualitative will be 
required only if HCV serology is positive. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
39 
Confidential 
24 July 2018 
Section 7.5.5 Electrocardiogram: 
Section updated to clarify that triplicate 12-lead electrocardiogram (ECG) collections should 
occur over a period of approximately 5 to 10 minutes. 
Section 8.0 Schedule of Procedures and Assesssments: 
Section updated to clarify that any patients enrolled in previous Part C/Phase 2 should follow the 
Phase 2 procedures and assessments and schedule of events. 
Section 8.1 Screening Evaluations: 
Section modified to remove text specific to Parts B and C as no longer applicable. 
Section updated to include collection of disease history information. 
Section modified to add information about obtaining a fresh biopsy or an archived tumor 
specimen plus a blood sample for patients in Phase 2. 
Section updated to clarify that triplicate 12-lead ECG collections should occur over a period of 
approximately 5 to 10 minutes. 
Section updated to clarify collection of blood samples for hepatitis testing. 
Section 8.2.1.1.1 Cycle 1 Day 1: 
Section updated to clarify that triplicate 12-lead ECG collections should occur over a period of 
approximately 5 to 10 minutes. 
Section modified to move predose blood collections for PK from within 60 minutes to within 
120 minutes prior to administration of ARRY-382. 
Section 8.2.1.1.3 Cycle 1 Day 15 (± 1 Day): 
Section modified to move predose blood collections for PK from within 60 minutes to within 
120 minutes prior to administration of ARRY-382. 
Section 8.2.1.2.1 Subsequent Cycles Day 1 (± 2 days): 
Section updated to clarify that triplicate 12-lead ECG collections should occur over a period of 
approximately 5 to 10 minutes. 
Section modified to move predose blood collections for PK from within 60 minutes to within 
120 minutes prior to administration of ARRY-382. 
Section modified to clarify that tumor assessments should be performed once every 6 weeks 
(± 7 days). 


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CCI


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
41 
Confidential 
24 July 2018 
Section 8.7 Collection of Data for Ongoing Patients Following Database Lock: 
Table 10 (Schedule of Events [Part A/Phase 1b]) footnotes updated to reflect the changes to the 
schedule of procedures and assessments for Part A described above. 
Previous Tables 10 and 11 deleted as no longer applicable.  
Table 11 (Schedule of Events [Phase 2]) added to include the schedule of procedures and 
assessments for Phase 2. 
Section 9.3 Replacement of Patients: 
Section updated with administrative changes/corrections. 
Section updated to add information about replacement of patients in the cohorts of Phase 2. 
Section 10.0 Safety Monitoring: Definitions and Reporting:  
Section heading updated to reflect updated Sponsor language. 
Section 10.1 Adverse Events: 
Section updated to reflect updated Sponsor terminology. 
Previous Section 10.1.2 Adverse Events Related to Subsequent Anticancer Therapy: 
Section removed to reflect updated Sponsor terminology. 
Section 10.2 Assessment of Severity: 
Section updated to clarify that severity of each AE will be determined by the Investigator and to 
reflect updated Sponsor terminology. 
Section 10.3 Assessment of Causality: 
Section updated with administrative changes/corrections. 
Section 10.4 Assessment of Seriousness: 
Section updated to reflect updated Sponsor terminology. 
Section 10.5 Reporting of Serious and Nonserious Adverse Events: 
Sponsor language regarding documentation of AEs updated. Section also updated with 
administrative changes/corrections. 
Section 10.6 Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs): 
Section heading and section updated to reflect updated Sponsor terminology. 
Section 10.7 Pregnancy or Drug Exposure During Pregnancy: 
Section updated to reflect updated Sponsor terminology. 


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CCI


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
43 
Confidential 
24 July 2018 
APPENDIX 7 IMMUNE-RELATED RESPONSE CRITERIA IN SOLID TUMORS:  
Section updated to correct the definition of confirmation of progression as representing an 
increase in tumor burden ≥ 25% compared with nadir at 2 consecutive time points at least 
4 weeks apart (was incorrectly noted as 2 weeks apart). 


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CCI


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
46 
Confidential 
24 July 2018 
higher PDL1 expression based on an FDA-approved test, and who do not express EGFR/ALK 
mutations. Additionally, the pembrolizumab label was expanded to include patients with lower 
PD-L1 expression (TPS ≥1%) who progressed on prior platinum therapy. 
Section 2.4 Dose Selection 
Clarified dosing for Pembrolizumab: In Parts A and B, pembrolizumab will be administered at 
the dose of 2 mg/kg intravenous infusion over 30 minutes every 3 weeks.  
In Part C, pembrolizumab will be administered at the approved dose of 200 mg intravenous 
infusion over 30 minutes every 3 weeks according to the Prescribing Information for Keytruda® 
(pembrolizumab). 
Section 4.1 Study Design Overview 
Table 5 was updated to remove ambiguity of cohort names and dose levels. The name of the first 
cohort is "Cohort 1", and the name of the second cohort is "Cohort 2". The dose of ARRY-382 in 
Cohort 2 will depend on the number of patients with DLTs. 
Section 4.2 Dose-limiting Toxicities (Part A) 
Table 6 was revised for consistency with the pembrolizumab label. 
Added: Patients who require a dose interruption or reduction during the initial 21-day treatment 
period (Cycle 1) will remain evaluable for tolerability decisions if the reason for the reduction 
and/or interruption represents a DLT. Patients will be replaced if they have received less than 
67% dose intensity [(administered dose in mg/planned dose in mg) x 100] of ARRY-382 or if 
they did not receive pembrolizumab for any reason other than an AE or abnormal laboratory 
value that is not related to disease, disease progression, intercurrent illness or concomitant 
medications/therapies before completing Cycle 1. 
Section 5.2.1 Inclusion Criteria 
Inclusion criterion #3 was revised for consistency with the pembrolizumab label. Language was 
added to allow patients on study who have front-line treatment with pembrolizumab in those 
with advanced NSCLC; TPS percentage of 50% is also stated for clarity. 
Section 5.2.2 Exclusion criteria 
Exclusion criterion #1 was revised due to change in treatment for patients which have adjuvant 
ipilimumab treatment. Language was added to clarify that prior treatment with ipilimumab is 
allowed under the conditions shown. 
Patients with ocular melanoma are excluded. 
Section 6.3.2 ARRY-382 Dose Modifications 
Language was added to allow decreasing doses from ≥ 400 mg QD to 300, 200 or 100 mg QD 
for Parts B and C. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
47 
Confidential 
24 July 2018 
Section 6.3.3 Pembrolizumab Dose Modifications 
Updated label reference from 2014 to OCT 2016 
Section 7.3.1 Macrophages, T Cells, and Other Immune Markers in Tumor Tissue 
Language was added to allow the option of punch biopsies or core needle biopsies. 
Section 7.4 PK Assessments 
Added the following to allow more flexibility with obtaining PK samples: Predose PK samples 
must be collected within 60 minutes prior to administration of ARRY-382. Postdose PK samples 
will be collected at 1hr (±5 min), 2hr (±10 min), 4hr (±20 min), and 8hr (±30 min) after 
administration of ARRY-382 on Cycle 1 Day 1 and Cycle 2 Day 1.  Trough PK blood samples 
will be collected predose on Cycle 1 Day 15 and Day 1 of Cycles 3 through 6. 
Section 8.7 Collection of Data for Ongoing Patients Following Database Lock 
Modified the text in order to allow more flexibility in procedures and data collection following 
database lock: If the primary objective of the study has been met or the Sponsor decides to stop 
the study early, the database may be locked for the purpose of analyzing and reporting data. 
Patients may continue to receive study treatment per protocol beyond database lock if the 
Investigator and the Sponsor agree that patients’ best interests are served by continuing to 
receive study treatment. In patients who continue on study treatment, the Sponsor may decide to 
only follow for safety (i.e., collect only SAE information, not require any study-specific 
procedures, and mandate that patients be followed according to standard-of-care), where 
allowable per local laws or jurisdictions. 
Section 9.3 Replacement of Patients 
Modified the text to indicate patients who do not receive a dose intensity of at least 67% of study 
drug will be replaced: For Part A, patients will be replaced if they have received less than 67% 
dose intensity [(administered dose in mg/planned dose in mg) x 100] of ARRY-382 or if they did 
not receive pembrolizumab for any reason other than an AE or abnormal laboratory value that is 
not related to disease, disease progression, intercurrent illness or concomitant 
medications/therapies before completing Cycle 1. 
Other minor changes/corrections in the protocol text, tables and footnotes were made for 
consistency and/or clarifications. 
Appendix 3 
Minor corrections made to align with reference publication. 
 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
48 
Confidential 
24 July 2018 
1.0 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
The Investigator at each investigational site is responsible for the conduct of the study. A 
subinvestigator is any member of the clinical study team designated and supervised by the 
Investigator to perform critical study-related procedures and/or to make important study-related 
decisions. 
Prior to study initiation, the Investigator at each site must provide to Array BioPharma Inc. 
(Array BioPharma/Sponsor) a signed protocol signature page, a fully executed and signed United 
States Food and Drug Administration (FDA) Form 1572, a current curriculum vitae (CV), 
medical license, and a financial disclosure form. Financial disclosure forms, current CVs and 
medical licenses must also be provided for all subinvestigators listed on Form 1572 who will be 
directly involved in the treatment or evaluation of patients in this study. 
The study will be administered and monitored by employees or representatives of Array 
BioPharma and/or a contract research organization (CRO) in accordance with all applicable 
regulations. Clinical research associates will monitor each site on a periodic basis and perform 
verification of source documentation for each patient. The Array BioPharma Drug Safety 
Department (and/or the CRO, if applicable) will be responsible for ensuring timely reporting of 
expedited serious adverse event (SAE) reports to regulatory authorities and Investigators. 


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2.0 
INTRODUCTION 
2.1 
Background Therapeutic Information 
Recent advances in immunobiology have resulted in novel agents with potent antitumor activity 
in patients with solid tumors. The tumor microenvironment, comprised of the tumor cells, 
fibroblasts, immune inflammatory cells, and endothelial cells, plays an important role in 
suppressing the immune system, leading to decreased antitumor effects. Increasing evidence 
suggests that interactions between cancer cells, stromal cells, macrophages, and the extracellular 
matrix are pivotal to the processes of tumorigenesis, metastasis, and neovascularization. 
Colony-stimulating factor 1 receptor (CSF-1R, also known as the cellular homolog of the 
V-FMS oncogene product of the Susan McDonough strain of feline sarcoma virus [cFMS]), is 
the primary receptor for colony-stimulating factor 1 (CSF-1), a regulator of the survival and 
proliferation of mononuclear phagocytes from undifferentiated precursors to fully differentiated 
nondividing macrophages (Stanley et al 1997). Binding of CSF-1 to the CSF-1R extracellular 
domain induces receptor dimerization and trans-autophosphorylation of the intracellular kinase 
domain. Expression of CSF-1R is robust on monocytes, tissue macrophages, and osteoclasts. 
Therefore, CSF-1 inhibitors may be useful in treating diseases in which osteoclasts and 
macrophages play a pathogenic role, such as cancer, autoimmune/inflammatory disease, and 
bone-related diseases. 
Tumor-associated macrophages (TAMs) were once thought to play a beneficial role in 
controlling cancer, engulfing tumor cells and mounting an immune response to cancer by 
presenting tumor antigens to effector T-cells. More recently, however, emerging data suggest 
that subsets of tumor macrophages, particularly those with M2 polarization, promote tumor 
progression by suppressing immune response and promoting angiogenesis, tumor cell migration, 
and invasion (Qian and Pollard 2010; Mantovani et al 2002). Consistent with these findings, the 
presence of tumor macrophages (particularly M2-polarized TAMs) and increased levels of 
CSF-1 and CSF-1R, have been associated with poor prognosis and survival in a number of 
cancer types, including breast (Leek et al 1996; Kluger et al 2004; Tsutsui et al 2005), ovarian 
(Shah et al 2008; Huang et al 2002), prostate (Lissbrant et al 2000), and lung cancers (Takanami 
et al 1999; Chen et al 2005; Kaminska et al 2006). CSF-1 promotes the differentiation of 
myeloid progenitors into monocytes, macrophages, dendritic cells, and osteoclasts. In the 
periphery, CSF-1 regulates the migration, proliferation, function, and survival of macrophages 
(Hume and MacDonald 2012).  
Critical drivers of immune escape in the tumor microenvironment include TAMs, monocytic 
myeloid-derived suppressor cells (Mo-MDSCs) and granulocytic MDSCs (Zhu et al 2014). 
Tumor-associated macrophages and MDSCs are both regulated in part by CSF-1, which signals 
via its receptor (i.e., CSF-1R). Depleting or modifying these regulatory cells has been shown to 
reverse immunosuppression in nonclinical models (Devaud et al 2013). Based on the role of 


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CSF-1R in promoting tumor cell-induced osteolysis, angiogenesis, and macrophage-stimulated 
tumor invasion, selective inhibition of CSF-1R presents an attractive therapeutic approach for the 
treatment of patients with cancer.  
2.1.1 
PD-1 and PD-L1 Inhibitor Resistance 
Despite strategies aimed at harnessing the immune system to fight cancer, the majority of 
patients that are treated with immune checkpoint inhibitors (CPIs) fail to respond. One 
mechanism that is utilized for primary (or intrinsic) resistance to these treatments is the ability of 
the tumor to avoid recognition by the immune system, preventing infiltration of immune cells 
into the tumor microenvironment (TME) which therefore cannot elicit an immune response 
against the tumor (Kim and Chen 2016). Studies have shown that an intrinsic or primary 
resistance to anti-programmed cell death receptor 1 (PD-1) therapy arises from immune 
regulatory factors in the tumor microenvironment which suppress specific immune responses to 
the tumor or which allows the tumor to evade recognition all together (Restifo et al 2016; Jenkins 
et al 2018). Hugo et al 2016 revealed an innate PD-1 resistance signature (“IPRES”) at the heart 
of anti-PD-1 nonresponders, in which tumors displayed elevated immunosuppressive factors like 
interleukin (IL)-10 and other anti-inflammatory molecules which likely contribute to the overall 
evasion of the tumor from an immune response. Furthermore, they suggested that genetic data 
from The Cancer Genome Atlas database indicate that only a subset of tumors display the IPRES 
(lung renal cell, pancreatic and colon carcinomas). One strategy is to turn these “cold” tumors, 
which have minimal immune cell infiltrate, into “hot” tumors by reducing or inhibiting the 
immunosuppressive factors present in the TME. Zhu et al 2014 found that CSF-1R inhibition    
in preclinical models not only decreased the number of tumor infiltrative macrophages (e.g., 
TAMs) in the TME, but improved the response to PD-1 inhibitor treatments and converted 
macrophages to support T-cell activation and increase antigen presentation. Thus, these data 
suggest that CSF-1R inhibition may be able to contribute to the repopulation of infiltrative T-
cells and other pro-inflammatory cells in the TME resulting in the ability to respond to PD-
1/programmed cell death ligand 1 (PD-L1) inhibition.   
2.1.2 
Malignant Melanoma 
For more than 30 years, cytotoxic chemotherapies and biologic agents such as IL-2 and 
interferon (alone and in combinations) have been used to treat unresectable, metastatic or 
advanced melanoma. Progress has been made with the regulatory approval of ipilimumab in 
2011 and other immune CPIs. Programmed cell death receptor 1 is a well described immune 
checkpoint protein that is a negative regulator of T-cell activity, and when bound to its ligands, 
PD-L1 and programmed cell death ligand 2 (PD-L2), is a negative regulator of cytokine 
production and T-cell proliferation. Pembrolizumab and nivolumab are monoclonal antibodies 
(mAbs) targeted to PD-1 that act to block the interaction between PD-1 and its ligands, PD-L1 
and PD-L2. Both CPIs were approved by the FDA for the treatment of melanoma in 2014. The 


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combination of ipilimumab and nivolumab for the treatment of metastatic melanoma 
demonstrated impressive antitumor activity, including a median progression-free survival (PFS) 
of 11.5 months and an objective response rate (ORR) of approximately 58% (Larkin et al 2015), 
albeit with increased toxicity over single-agent therapy.  
2.1.3 
Non-Small Cell Lung Carcinoma 
Lung cancer is the most common cause of death from cancer with an estimated 264,800 and 
157,423 cancer deaths per year in Europe and the United States (US), respectively (Ferlay et al 
2013; U.S. Cancer Statistics Working Group 2015). For patients with advanced disease, first-line 
therapies, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) 
in patients with EGFR mutations, and platinum-based chemotherapy, have shown improved 
survival outcomes. However, most of these patients progress and require second-line therapy 
with a chemotherapy-based regimen. Until recently, docetaxel and pemetrexed have been 
standard second-line treatment regimens for non–small cell lung cancer (NSCLC) and have 
demonstrated a median PFS of 3 months (Hanna et al 2004). In early clinical trials, anti-PD-1 
and anti-PD-L1 antibodies produced durable responses in 20% of unselected patients with 
advanced NSCLC (Brahmer et al 2012; Topalian et al 2012). Pembrolizumab, a PD-1–blocking 
antibody, was initially approved for a NSCLC indication in 2015 on the basis of a subgroup 
analysis within a larger trial. Those patients who had received a prior platinum-based 
chemotherapy regimen and had tumors expressing PD-L1 with a tumor proportion score (TPS) 
of ≥ 50% achieved a median PFS of approximately 6.1 months and an ORR of approximately 
44% (Garon et al 2015). It was recently reported that in a study of patients with advanced 
NSCLC who had received a prior platinum-based chemotherapy regimen, pembrolizumab 
(2 mg/kg every 3 weeks [Q3W]) resulted in a median PFS of 5.0 months and an ORR of 30% in 
patients with TPS ≥ 50%, generally confirming the earlier study (Herbst et al 2016). Based on 
results from the KEYNOTE-024 study, a Phase 3 trial that evaluated the efficacy of 
pembrolizumab versus platinum-based chemotherapy as first-line treatment for metastatic 
NSCLC that expressed PD-L1, the FDA recently approved the use of single-agent 
pembrolizumab for the frontline treatment of metastatic NSCLC in patients who have 50% or 
higher PD-L1 expression based on an FDA-approved test, and who do not express 
EGFR/anaplastic lymphoma kinase (ALK) mutations. In patients treated with pembrolizumab, 
the median PFS was 10.3 months, and the ORR was 44.8%. The estimated rate of overall 
survival at 6 months was 80.2% (Reck et al 2016). Additionally, the pembrolizumab label was 
expanded to include patients with lower PD-L1 expression (TPS ≥ 1%) who progressed on prior 
platinum therapy (Keytruda® [pembrolizumab] summary of product characteristics). In the 
KEYNOTE-001 study, in the cohort of treatment-naïve NSCLC patients with tumor TPS of 1% 
to 49%, the ORR was 17%, the median PFS was 4.2 months, and the PFS rate at 12 months was 
25% (Hui et al 2017). In May 2017, pembrolizumab was also approved under accelerated 
approval in combination with pemetrexed and carboplatin as first-line treatment of patients with 


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metastatic nonsquamous NSCLC, irrespective of PD-L1 expression (Keytruda® 
[pembrolizumab] summary of product characteristics).  
2.1.4 
Ovarian Cancer  
Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any 
other cancer of the female reproductive system (American Cancer Society 2018). Despite 
surgery and platinum- and taxane-based chemotherapies, greater than 70% of patients with 
advanced ovarian cancer who achieve remission ultimately experience relapse. Because there are 
few effective treatments for these patients the development of new treatment strategies is 
urgently required (Hamanishi et al 2015). In platinum-resistant ovarian cancer (prOVCA), 
current standard-of-care includes single-agent chemotherapeutic agents which have ORRs of 
20% to 25% and median PFS of approximately 3 months (Herzog and Monk 2017). In a recent 
Phase 3 study, bevacizumab added to chemotherapy resulted in ORR of 27% and PFS of 
6.7 months (Pujade-Lorraine et al 2014). 
In recent years, there has been some progress made with achieving response with 
immunotherapy. In the KEYNOTE-028 trial of pembrolizumab in patients with advanced solid 
tumors, data were reviewed for the 26 patients enrolled with PD-L1-positive ovarian cancer. In 
this patient population, the ORR was 11.5% with 1 complete response (CR) and 2 partial 
responses (PRs) achieved. Median PFS and overall survival (OS) were 1.9 months and 
13.1 months, respectively (Varga et al 2017). Results are pending for a follow-up Phase 2 study 
(KEYNOTE-100; NCT02674061) in women with advanced ovarian cancer (ClinicalTrials.gov 
NCT02674061).  
2.1.5 
Pancreatic Cancer 
Pancreatic cancer is one of the most treatment-resistant human malignancies, due in part to its 
heterogenic tumor microenvironment. Patients with pancreatic ductal cancer have extremely 
poor prognoses with the 5-year survival rate of 5–20% of patients who undergo a potentially 
curative operation (Nakata et al 2002). The existing treatment modalities, including surgical 
resection and conventional chemotherapies, prolong survival but fail to cure the disease 
(Johansson et al 2016). A number of immunotherapeutic agents are currently being tested in 
patients with pancreatic cancer. In unselected patients, cytotoxic T-lymphocyte antigen 4 
(CTLA-4) inhibitors and PD-1/PD-L1 inhibitors appear to have limited activity with best 
response of stable disease (Johansson et al 2016). In patients with microsatellite instability high 
(MSI-H) pancreatic ductal cancer, partial responses were observed in 5/6 (83%) patients 
(Keytruda® [pembrolizumab] summary of product characteristics). Recently, the combination of 
the PD-1 inhibitor nivolumab and the antibody targeting CSF-1R, cabiralizumab, resulted in an 
overall ORR of 13% in 30 patients with microsatellite stable (MSS) pancreatic cancer. The 


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safety profile of the combination was generally tolerable and consistent with nivolumab and 
cabiralizumab monotherapy (Wainburg et al 2017).  
2.2 
Investigational Medicinal Product 
ARRY-382 is a potent, highly specific, orally available small-molecule inhibitor of CSF-1R (also 
known as cFMS) kinase activity. 
2.2.1 
Nonclinical Studies with ARRY-382 
Detailed information regarding nonclinical studies of ARRY-382 is presented in the 
Investigator’s Brochure. 
2.2.1.1 
Nonclinical Pharmacology 
The biological activity of ARRY-382 has been evaluated in a panel of cell culture and in vivo 
studies. In cellular studies, ARRY-382 was a potent inhibitor of CSF-1R (concentration required 
for 50% inhibition [IC50] = 9 nM). In cell culture experiments, ARRY-382 markedly inhibited 
the CSF-1R pathway both mechanistically and functionally. Using human osteoclast precursor 
cells, ARRY-382 was shown to significantly inhibit osteoclast differentiation and bone 
resorption in vitro. 
In vivo, ARRY-382 was evaluated for its ability to inhibit inflammatory processes and CSF-1R 
phosphorylation in human embryonic kidney cell line (HEK-293) cells. In a 
lipopolysaccharide-induced cytokine model in mice, single administrations of 3, 10, 30, and 
100 mg/kg significantly inhibited tumor necrosis factor-alpha (TNF-α) production. In a 
pharmacodynamics model (engineered HEK-293 cell line expressing doxycycline-induced 
CSF-1R), the dose required for 50% of the maximum effect (ED50) of ARRY-382 was 3 mg/kg. 
ARRY-382 was also efficacious in inhibiting osteolytic bone destruction and allodynia in a 
breast cancer bone metastasis model. 
Based on in vitro metabolism studies, ARRY-382 in humans is predicted to be eliminated by 
multiple metabolic pathways and enzymes including Phase 1 (cytochrome P450 [CYP] 3A4 and 
flavin-containing monooxygenase [FMO] 1, 3, and 5) and Phase 2 metabolism. Human 
recombinant CYPs responsible for the metabolism of ARRY-382 include primarily CYP3A4, but 
also included CYP2C9, CYP2C19, and CYP2D6. ARRY-382 was a substrate for permeability 
glycoprotein (P-gp) expressed in pig kidney epithelial cell line (LLC-PK1) cells and may be an 
inhibitor of P-gp at concentrations greater than 30 µM. 


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2.2.1.2 
Nonclinical Safety and Toxicity 
Safety pharmacology studies were conducted to assess the effects of ARRY-382 on 
cardiovascular function. In the in vitro human ether a-go-go gene (hERG) channel assay, 
ARRY-382 showed a free IC50 of 4.12 μg/mL. This is significantly higher than the expected 
unbound plasma concentration of ARRY-382 at a dose of 400 mg, which is approximately 
100 ng/mL. These results indicate a low risk of hERG channel-influenced conduction 
abnormalities.  
In vivo, cynomolgus monkeys received single oral doses of 0, 10, 30, or 100 mg/kg ARRY-382. 
The only cardiovascular change noted was a marked increase in QT interval corrected for heart 
rate (QTc) interval observed in 1 of the 6 animals treated at the highest dose level (i.e., 
100 mg/kg). Although values for QT interval and QTc for other animals treated at the high dose 
level were not affected, a potential effect of ARRY-382 on ventricular repolarization could not 
be fully excluded at the dose of 100 mg/kg. 
Two toxicity studies have been conducted in accordance with international regulatory guidelines 
for nonclinical toxicity studies and in adherence to current Good Laboratory Practice (GLP) 
guidelines. ARRY-382, administered orally at doses up to 300 mg/kg/day in rats and 
100 mg/kg/day in cynomolgus monkeys, demonstrated an acceptable safety profile in both 
studies.  
The no observed adverse effect level (NOAEL) for daily oral dosing of ARRY-382 in rats for 
28 days was 30 mg/kg/day (180 mg/m2). Findings in rats included dose-related elevations in 
alanine transaminase (ALT), aspartate transaminase (AST), sorbitol dehydrogenase, and 
amylase, with no adverse effects in associated organs. Increased kidney weights at 300 mg/kg 
and decreased spleen weights at all doses of ARRY-382 were noted, but the significance of these 
findings is unclear. Statistically significant increases in adrenal gland weights were noted in 
males and females given 100 and 300 mg/kg, correlating with minimal to slight cortical 
hypertrophy that was histologically evident. Study-related stress may have contributed to 
increased adrenal gland weight. Other changes relating to increases or changes in macrophages 
and bone changes were consistent with the pharmacologic activity of ARRY-382. 
The NOAEL for daily oral dosing of ARRY-382 in cynomolgus monkeys for 28 days was 
10 mg/kg (120 mg/m2). Findings in monkeys included elevations in ALT, AST, and creatine 
kinase (CK) in animals receiving 30 and 100 mg/kg. Lower levels of amino-terminal 
crosslinking telopeptides of type I collagen (NTX) were noted in animals receiving 30 and 
100 mg/kg compared with pretest. A slight increase in bioactive parathyroid hormone (PTH) was 
also noted, though these data were highly variable. The only test-article-related macroscopic 
finding or change in organ weight was a statistically significant lower thymus weight in both 
sexes at 100 mg/kg, which appeared to be partly due to individual variations. None of these 


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Table 1: 
All Adverse Events Reported in ≥ 15% of All Patients (Clinical 
Study ARRAY-382-101)  
MedDRA  
Preferred Term 
25 mg  
QD 
(n=1) 
50 mg  
QD 
(n=1) 
100 mg 
QD 
(n=1) 
200 mg 
QD 
(n=6) 
400 mg 
QD 
(n=11) 
500 mg 
QD 
(n=6) 
Total 
(N=26) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Total patients with any AE 
1 (100) 
1 (100) 
1 (100) 
6 (100) 
11 (100) 
5 (83) 
25 (96) 
Fatigue 
1 (100) 
1 (100) 
1 (100) 
3 (50) 
7 (64) 
3 (50) 
16 (62) 
Nausea 
1 (100) 
1 (100) 
0 
1 (17) 
2 (18) 
3 (50) 
8 (31) 
Vomiting 
1 (100) 
1 (100) 
0 
1 (17) 
3 (27) 
2 (33) 
8 (31) 
Oedema peripheral 
0 
0 
0 
1 (17) 
4 (36) 
2 (33) 
7 (27) 
Blood creatine phosphokinase 
increased 
0 
0 
0 
0 
4 (36) 
3 (50) 
7 (27) 
Decreased appetite 
1 (100) 
0 
1 (100) 
0 
2 (18) 
2 (33) 
6 (23) 
Constipation 
0 
0 
0 
0 
2 (18) 
3 (50) 
5 (19) 
Dyspnoea 
0 
0 
0 
1 (17) 
2 (18) 
2 (33) 
5 (19) 
Anaemia 
0 
0 
0 
2 (33) 
1 (9) 
2 (33) 
5 (19) 
Pyrexia 
1 (100) 
0 
0 
1 (17) 
0 
2 (33) 
4 (15) 
Dehydration 
0 
0 
0 
0 
3 (27) 
1 (17) 
4 (15) 
Pruritus 
0 
0 
0 
1 (17) 
3 (27) 
0 
4 (15) 
Cough 
1 (100) 
0 
0 
0 
1 (9) 
2 (33) 
4 (15) 
Pneumonia 
1 (100) 
0 
0 
0 
2 (18) 
1 (17) 
4 (15) 
AE=adverse event; MedDRA=Medical Dictionary for Regulatory Affairs; QD = once daily 
 
Grade 1 increases in QT interval corrected for heart rate using Fridericia’s formula (QTcF) 
(absolute values) were observed in 9 (35%) of 26 patients, all of whom were in the higher dose 
levels (i.e., 200 mg QD, 400 mg QD, or 500 mg QD cohorts). Grade 1 increases (31 to 60 msec) 
from baseline in QTcF intervals were observed in 6 (23%) patients, and did not appear to be 
dose-related. No patient had a QTcF interval that exceeded 480 msec or an increase from 
baseline that exceeded 60 msec. 
Dose-limiting toxicities (DLTs) were reported for 1 of 11 patients in the 400 mg QD cohort 
(Grade 3 increase in blood CK) and 2 of 6 patients in the 500 mg QD cohort (Grade 2/3 increase 
in AST and Grade 3 pyrexia in 1 patient). The maximum tolerated dose (MTD) was determined 
to be 400 mg QD. 
2.2.2.2 
Clinical Pharmacokinetics 
In Study 101 (n=26 patients), concentrations of ARRY-382 and 3 metabolites (AR00469099 [an 
N-oxide metabolite], AR00649100 [an N-desmethyl metabolite], and AR00470870 [a sulfate 


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metabolite]) were measured. Exposure (maximum observed plasma concentration [Cmax] and 
area under the plasma concentration-time curve over the dosing interval [AUCτ]) to ARRY-382 
increased with increasing doses over the 25 mg to 500 mg QD dose range on Cycle 1 Day 1 and 
Day 15, with median time of the maximum observed plasma concentration (Tmax) values of 
approximately 2 hours across all doses at both time points. The overall median apparent terminal 
half-life (t1/2) values were 18 and 19 hours on Cycle 1 Day 1 and Day 15, respectively.  
For the 3 metabolites (AR00469099, AR00649100, and AR00470870), exposure (Cmax and 
AUCτ) to ARRY-382 increased with increasing doses over the 25 mg to 500 mg QD dose range 
on Cycle 1 Day 1 and Day 15. The overall median Tmax values for the 3 metabolites on Cycle 1 
Day 1 and Day 15 were approximately 4 and 5.5 hours, 2 and 2 hours, and 4 and 3 hours, 
respectively. 
A preliminary assessment of food effect on the exposure of ARRY-382 was included in 
Study 101. Plasma concentrations in samples collected 24 hours after administration of 
ARRY-382 in the fasted state (Cycle 1 Day 15) were compared with those in the fed state (with 
full or light meal, Cycle 1 Day 14). Information related to food consumption was collected using 
food diaries for each patient. Although there was no significant variation in trough plasma 
concentrations of ARRY-382 when administered in the fasted or fed condition, there was a trend 
toward increased exposure to ARRY-382 when administered with a heavy meal. Limitations of 
these findings included the long median t1/2 values (approximately 19 hours across all doses at 
Cycle 1 Day 15) and high intrapatient variability. 
2.2.2.3 
Clinical Biomarker Analysis 
In Study 101, biomarkers included CSF-1 and circulating cytokines, nonclassical monocytes 
(NCMs), CSF-1–stimulated extracellular signal-regulated kinase (ERK) phosphorylation in 
monocytes, markers of bone turnover, and circulating tumor cells (CTCs). Twenty-six patients 
were included in the blood pharmacodynamic population, and 25 patients were included in the 
urine pharmacodynamic population. However, data for each marker were not available for all 
patients, as noted in the following sections. 
2.2.2.3.1 
Markers of CSF-1R Inhibition 
Serum concentrations of CSF-1, as well as macrophage inflammatory protein 1 beta [MIP-1b], 
monocyte chemoattractant protein 1 [MCP-1], interleukin [IL]-8, IL-10, IL-6, and other 
circulating cytokines that are produced by or affect macrophages, were evaluated as potential 
markers of CSF-1R inhibition. For CSF-1, mean (standard deviation [SD]) percentage increases 
from baseline following treatment with ARRY-382 ranged from 328% (325) to 1845% (2022) 
and were observed at all time points. Increases in CSF-1 trended in a dose- and time-dependent 
manner, with minimal (< 2-fold) increases being observed for the lowest dose levels (25, 50, and 


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100 mg QD) and increases being higher and generally similar for the 400 and 500 mg QD dose 
levels. The maximum effect for the 2 highest dose levels was observed on Cycle 1 Day 22. 
Another potential marker of CSF-1 inhibition was the abundance of an NCM subpopulation in 
blood. Assessment of NCM subpopulation was not performed for the 25, 50, and 100 mg QD 
dose levels, and available data are limited to 15 patients in the higher dose cohorts (200, 400, and 
500 mg QD). Review of individual patient data indicated no notable changes in the percentage of 
total monocytes following treatment with ARRY-382. When the abundance of NCM was 
evaluated as a percentage of baseline at Cycle 1 Day 15, decreases were observed in all cohorts 
tested. Overall, the mean (SD) percentage of the NCM subpopulation was reduced to 15.2% 
(27.2) of the baseline value. Intermediate reductions in NCM subpopulation compared with 
baseline were observed in the 200 mg QD cohort, with a mean (SD) percentage of 35.5% (42.2) 
of the baseline value present on Cycle 1 Day 15. The largest reductions were observed for the 
400 and 500 mg QD cohorts, when the NCM subpopulation was reduced to mean (SD) values of 
4.3% (4.4) and 5.9% (2.4) of the baseline values, respectively. 
Finally, ex vivo CSF-1-stimulated ERK phosphorylation in circulating monocytes was also 
evaluated as a potential marker of CSF-1R inhibition. Data are not available for the 25 and 
100 mg QD dose levels due to sample processing issues. Inhibition of ERK phosphorylation 
relative to baseline was observed at each time point in all cohorts tested. At the time point 
corresponding with steady-state trough plasma concentrations of ARRY-382 (Cycle 1 Day 15 
predose), decreases in phosphorylated ERK were observed in a dose-dependent manner, with 
complete inhibition observed at the 400 and 500 mg QD dose levels. At the 200 mg QD level, 
complete inhibition was observed at 4 hours postdose on Cycle 1 Day 15. 
2.2.2.3.2 
Markers of Bone Turnover 
Urine concentrations of NTX, serum concentrations of NTX, and serum tartrate-resistant acid 
phosphatase 5b (TRAP5b) were evaluated as markers of bone turnover. Values of NTX 
> 64 nmol bone collagen equivalents (BCE)/mmol creatinine at baseline were classified as being 
elevated. Of 7 patients with elevated urinary NTX levels at baseline, 5 had reductions in absolute 
values to within the normal range (≤ 64 nmol BCE/creatinine) on or before Cycle 2 Day 1, 
including 2 patients with known bone metastases. Another patient with elevated urinary NTX 
levels at baseline and known bone metastasis had a reduction in absolute values to within the 
normal range by Cycle 3 Day 1. Mean NTX levels were reduced relative to baseline at all time 
points for the 100, 200, 400, and 500 mg QD cohorts. 
Review of individual patient data indicated a trend in serum NTX concentrations similar to that 
of urinary NTX and no notable changes in TRAP5b levels.  


ARRY-382 (CSF-1R inhibitor) 
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Version 4 
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2.2.2.3.3 
Markers of Metastasis 
Circulating tumor cells were quantified as a marker of intravasation and/or metastasis. Changes 
in the number of CTCs relative to baseline levels following treatment were variable, and no 
conclusions regarding the effect of ARRY-382 on CTCs was drawn. 
2.2.2.4 
Clinical Efficacy 
In Study 101 (n=26 patients), no objective responses were observed. Four patients with heavily 
pretreated cancer experienced a best response of stable disease, which lasted > 3 months for 
2 patients.    
2.3 
Rationale for the Current Study 
ARRY-382 is a potent, highly specific, orally available small molecule inhibitor of CSF-1R. 
Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the 
interaction between PD-1 and its ligands, PD-L1 and PD-L2. PD-1 is a well described immune 
checkpoint protein that is upregulated on tumors and acts as a negative regulator of T-cell 
activity and cytokine production, thereby suppressing immune-mediated surveillance of tumor 
growth (Postow et al 2015). Pembrolizumab acts to release the PD-1 pathway-mediated 
inhibition of the immune response, including the antitumor immune response.  
The exploration of ARRY-382 in combination with pembrolizumab is a logical approach to treat 
certain cancers by affecting a double-blockade of cancer-induced immune suppression through 
inhibition of 2 pathways that negatively regulate immune-mediated tumor control. Nonclinical 
studies have demonstrated that the T-cell antitumor responses elicited by treatment with 
anti-PD-L1 can be limited by immunosuppressive myeloid cells such as M2 macrophages. 
Treatment with ARRY-382 in mice bearing MCF-7 or MD-MB-231 breast carcinoma xenografts 
markedly reduced TAM infiltration into these tumors (data on file). Combining anti-PD-L1 with 
CSF-1R inhibitors (antibodies or small molecules) reverses this immune suppression and leads to 
a stronger anti-tumor response than that seen with anti-PD-L1 alone (Zhu et al 2014). In 
addition, studies with nonclinical tumor xenografts show that inhibition of CSF-1R kinase can 
augment antitumor responses (e.g., with chemotherapy or immunotherapy) (DeNardo et al 2011). 
Agents targeting CSF-1R in combination with anti-PD-1 or anti-PD-L antibodies are under 
active clinical development (ClinicalTrials.gov NCT02323191; ClinicalTrials.gov 
NCT02452424; ClinicalTrials.gov NCT02526017). 
2.3.1 
Phase 1b (Part A) 
The Phase 1b portion (Part A) of the study has a standard dose-escalation design to determine the 
MTD and/or recommended Phase 2 dose (RP2D) of ARRY-382 in combination with 
pembrolizumab. The patient population for Part A of this study will consist of patients with 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
60 
Confidential 
24 July 2018 
advanced/metastatic melanoma, PD-L1–positive NSCLC, ovarian cancer, triple-negative breast 
cancer, head and neck squamous cell cancer (HNSCC), bladder cancer, metastatic colorectal 
cancer (CRC), pancreatic ductal adenocarcinoma (PDA), or gastric cancer.  
Selection of the tumor types included in this portion of the study is based on evidence that 
increased TAM or signaling through the CSF-1 receptor is associated with poor outcome in these 
indications. Increased levels of CSF-1 and CSF-1R, have been associated with poor prognosis 
and survival in a number of cancer types, including breast (Leek et al 1996; Kluger et al 2004; 
Tsutsui et al 2005), ovarian (Shah et al 2008; Huang et al 2002), prostate (Lissbrant et al 2000), 
and lung cancers (Takanami et al 1999; Chen et al 2005; Kaminska et al 2006).  
Part A (Phase 1b) has been completed and the MTD/RP2D of ARRY-382 was determined to be 
300 mg QD in combination with pembrolizumab. A total of 19 patients were treated in Part A at 
doses of 200 mg QD (n=6), 400 mg QD (n=7) and 300 mg QD (n=6). Dose-limiting toxicities 
were observed in 2 patients at 400 mg QD, including Grade 3 CK increase in 1 patient and 
Grade 3 AST/ALT and bilirubin increase in another patient. One patient treated at 300 mg QD 
experienced a DLT of Grade 3 pancreatitis. There were 2 confirmed responses including 
1 patient with PDA treated at the 200 mg dose level and 1 patient with ovarian cancer at the 
300 mg dose level. In addition to the patients with objective responses per the Response Criteria 
in Solid Tumors, version 1.1 (RECIST 1.1), tumor regressions were observed in 1 patient with 
melanoma and 2 patients with ovarian cancer (Harb et al 2017). 
2.3.2 
Phase 2  
The purpose of the Phase 2 cohorts of the study is to assess whether the efficacy of 
pembrolizumab can be enhanced with the addition of ARRY-382 at the RP2D in these patient 
populations.  
The Phase 2 PD-1/PD-L1 Inhibitor Refractory cohort is based on nonclinical data that suggests 
that CSF-1R inhibition can increase infiltrating T-cells and other pro-inflammatory markers that 
may enhance the effects of a PD-1 inhibitor (Section 2.1.1). All tumor types to be included are 
those in which PD-1/PD-L1 inhibitors are currently being used and are consistent with the 
indications selected in Part A of the study. 
The Phase 2 prOVCA and PDA cohorts are based on the preliminary activity that was observed 
in Part A suggesting that the addition of ARRY-382 to pembrolizumab may be effective in 
patients with ovarian cancer and in patients with PDA in whom effective therapies are not 
available. In Part A (dose-escalation) of this study, all 3 patients with ovarian cancer in the study 
achieved tumor regression with 1 patient experiencing a PR. The only other response in Part A 
was observed in a patient with PDA who had been treated with 2 prior lines of therapy who 
remained on study for greater than 17 cycles.  


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
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2.4 
Dose Selection 
ARRY-382: 
For Part A, the starting dosage of ARRY-382 is 200 mg QD by mouth (po), with planned 
escalation to 400 mg QD.  
The starting dosage of ARRY-382 in this study is 50% of the MTD identified in Study 101. In 
that study (see Section 2.2.2), evidence of biologic activity, including decreases in ex vivo 
CSF-1-stimulated phosphorylated ERK in monocytes and decreased numbers of NCM, was 
observed in patients treated at dose levels of 200 mg QD or higher. Maximal inhibition of these 
markers was observed at the 400 mg QD and 500 mg QD dose levels. Reductions in urinary 
levels of NTX were observed at dose levels of 50 mg QD and higher.  
In Phase 2, the dose of ARRY-382 will be 300 mg QD, the MTD/RP2D determined during 
Part A (see Section 2.3.1), in combination with pembrolizumab. 
Pembrolizumab: 
In Part A, pembrolizumab will be administered at the dose of 2 mg/kg intravenous (iv) infusion 
over 30 minutes Q3W.  
In Phase 2, pembrolizumab will be administered as 200 mg iv infusion over 30 minutes (within -
5 to +10 minutes) Q3W. 
 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
67 
Confidential 
24 July 2018 
4.0 
STUDY DESIGN 
4.1 
Study Design Overview 
This is an open-label, multicenter Phase 1b/2 study to determine the MTD and/or RP2D of 
ARRY-382 in combination with pembrolizumab in adult patients with selected advanced solid 
tumors (Part A/Phase 1b); and to estimate the efficacy of the combination in patients with 
advanced solid tumors that have progressed on prior PD-1/PD-L1 inhibitors, in patients with 
prOVCA and in patients with PDA (Phase 2). 
Each phase of the study consists of a 28-day screening period; 21-day treatment cycles with the 
combination of ARRY-382 and pembrolizumab until disease progression as determined by the 
Investigator, unacceptable toxicity, withdrawal of consent, or death (or other discontinuation 
criteria are met [see also Section 9.2]); and a 30-day safety follow-up period. Patients in all 
cohorts/phases will be monitored for OS until 1 year after the date of the last patient’s first visit. 
Part A (Phase 1b) includes a dose-escalation component with 2 planned dose cohorts (Table 6). 
Oral doses of ARRY-382 will be administered QD in combination with pembrolizumab 2 mg/kg 
iv Q3W. Patients in Cohort 1 will be enrolled on a rolling basis up to 6 evaluable patients or until 
DLTs (see Section 4.2) are observed in more than 1 patient during Cycle 1. If fewer than 2 of 
6 patients experience a DLT during Cycle 1, patients in Cohort 2 will receive ARRY-382 400 
mg QD. If 2 or more patients in Cohort 1 experience DLTs during Cycle 1, the dosage of 
ARRY-382 in Cohort 2 will be 100 mg QD. If a Grade 3 immune-related AE (irAE) (first 
occurrence) is reported in a given cohort, enrollment in that cohort will continue at the same dose 
until the toxicity is evaluated. If a second Grade 3 irAE is reported or a first Grade 3 irAE is 
reported in addition to a previous DLT in a given cohort, enrollment of new patients in that 
cohort will be stopped until the Grade 3 irAE is evaluated. If the event is not a DLT (as 
determined by the Investigators in consultation with the Sponsor), then enrollment may be 
resumed, or the cohort may be expanded to include up to 9 patients. If the Grade 3 irAE is 
deemed a DLT, the MTD has been achieved and additional patients will be enrolled at the 
previous dose level or at an intermediate dose level.  
Intermediate doses and doses higher than 400 mg QD may also be considered upon review of the 
safety and PK results from the planned dose cohorts.  


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
68 
Confidential 
24 July 2018 
Table 6: 
Planned Dose Cohorts (Part A) 
 
Planned dose regimen 
ARRY-382 
Pembrolizumab 
Cohort 1 
200 mg po QD 
2 mg/kg iv every 3 weeks 
Cohort 2 
If patients with DLTs ≥ 2 of 6 in Cycle 1: 
100 mg po QD 
2 mg/kg iv every 3 weeks 
If patients with DLTs ≤ 1 of 6 in Cycle 1: 
400 mg po QD 
2 mg/kg iv every 3 weeks 
DLT = dose limiting toxicity; iv = intravenously; kg = kilogram(s); mg = milligram(s); po = by mouth; Q3W = every 3 weeks; 
QD = once daily 
 
In the absence of identification of an MTD, a dose of 400 mg or lower may be selected as the 
RP2D as long as the DLT rate is < 33% (e.g., fewer than 2 of 6 patients experience a DLT).  
Part A has been completed and the MTD/RP2D of ARRY-382 was determined to be 300 mg QD 
in combination with pembrolizumab. Cohorts evaluating patients with metastatic melanoma 
(previous Part B) and PD-L1-positive NSCLC (previous Part C) were removed by protocol 
amendment after enrollment of 1 patient in each cohort due to changes in the respective 
treatment paradigms. 
Phase 2 will consist of 3 separate cohorts of patients. The Phase 2 PD-1/PD-L1 Inhibitor 
Refractory cohort will consist of patients with advanced solid tumors who progressed on a 
PD-1/PD-L1 inhibitor-containing regimen as their most recent prior line of therapy are who are 
naïve to prior CSF-1R or CSF-1 inhibitors. The Phase 2 prOVCA and PDA cohorts will consist 
of patients with prOVCA and patients with PDA, respectively, who have had at least one prior 
line of therapy and who are naïve to prior checkpoint inhibitor (CPI) therapy and to prior CSF-
1R or CSF-1 inhibitors.  
In Phase 2, at baseline, submission of archived tumor tissue from the most recent sample 
collection available or a fresh biopsy will be required.  
All patients in Phase 2 will receive ARRY-382 at 300 mg QD, the MTD/RP2D determined 
during Part A, in combination with pembrolizumab 200 mg iv Q3W. 
Efficacy assessments include determination of objective response using RECIST v1.1. For 
patients who have initial evidence of radiological progressive disease (PD) by RECIST v1.1, it 
will be at the discretion of the Investigator to keep a patient on study treatment or to stop study 
treatment until repeat imaging is performed approximately 4 weeks later in order to confirm PD 
per irRC. Patients with confirmed irPD should discontinue treatment. Patients with a declining 
Eastern Cooperative Oncology Group performance status (ECOG PS), deteriorating clinical 
symptoms or rapid progression of disease/progression at critical anatomical sites (i.e., central 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
70 
Confidential 
24 July 2018 
Table 7: 
Dose-Limiting Toxicities (Part A) 
Toxicity 
DLT Definition Criteria 
Nonhematologic AEs 
• 
Recurring Grade 2 pneumonitis 
• 
Grade 3 irAE that does not resolve or return to baseline with 
immunosuppressive therapy within 28 days of onset 
• 
Grade 3 QTcF prolongation or > 60 msec increase in QTcF over baseline 
• 
Grade 3 rash that does not resolve or return to baseline in <10 days with 
symptomatic management 
• 
Any other Grade 3 or 4 nonhematologic AE, with the following exceptions: 
o 
Alopecia  
o 
Grade 3 nausea, diarrhea, or vomiting lasting less than 72 hours with 
optimal medical management 
o 
Grade 3 AE of tumor flare or pseudoprogression (defined as local pain, 
irritation, or rash localized at sites of known or suspected tumor) 
o 
Grade 3 endocrinopathy that is adequately controlled by hormonal 
replacement 
Hematology AEs/ 
Laboratory abnormalities 
• 
Any Grade 4 hematologic AEs or Grade 4 laboratory abnormalities, with the 
following exceptions: 
o 
Grade 4 lymphopenia 
o 
Grade 4 neutropenia lasting ≤ 48 hours that is not associated with fever or 
other clinically significant symptoms 
o 
Isolated Grade 4 electrolyte imbalances/abnormalities that are not 
associated with clinical sequelae and are corrected with 
supplementation/appropriate management within72 hours of onset 
• 
Grade 3 thrombocytopenia with clinically significant bleeding that requires 
platelet transfusion 
• 
Febrile neutropenia defined as a fever with or without clinically or 
microbiologically documented infection with absolute neutrophil count 
(ANC) < 1.0 × 109/L, and a fever ≥ 38.5 °C  
• 
Any Grade 4 AST or ALT elevation unless clearly attributable to disease 
progression  
• 
Grade 3 AST or ALT elevation lasting > 7 days unless clearly attributable to 
disease progression 
• 
Grade 3 AST or ALT elevation associated with bilirubin levels ≥ 2 × ULN or 
an international normalized ratio (INR) > 1.5 unless clearly attributable to 
disease progression  
• 
Any Grade ≥ 3 bilirubin elevation unless clearly attributable to disease 
progression 
• 
CK elevation ≥ Grade 3 lasting > 7 days OR associated with an increase in 
creatinine ≥ 1.5 × the baseline value for creatinine 
Dose delay 
• 
Interruption of dosing for greater than 14 days, if due to AEs not related to 
the underlying disease or intercurrent illness 
Other 
• 
Inability to receive at least 67% of protocol-specified doses of ARRY-382 
during Cycle 1 due to AEs not related to the underlying disease or 
intercurrent illness 
AE = adverse event; ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; 
CK = creatine kinase; DLT = dose-limiting toxicity; INR = International Normalized Ratio; irAE = immune-related adverse 
event; QTcF = QT interval corrected for heart rate using Fridericia’s formula; ULN = upper limit of normal  


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
71 
Confidential 
24 July 2018 
For the purposes of dose escalation and determination of the MTD in Part A, only DLTs that 
occur during Cycle 1 will be necessarily considered for decisions regarding dose escalation. 
Other clinically significant toxicities or TEAEs that meet the definition of DLT occurring after 
Cycle 1 (i.e., dose-modifying events) may be considered when determining the RP2D.  
In Part A, patients who require a dose interruption or reduction during the initial 21-day 
treatment period (Cycle 1) will remain evaluable for tolerability decisions if the reason for the 
reduction and/or interruption represents a DLT. Patients will be replaced if they have received 
less than 67% dose intensity [(administered dose in mg/planned dose in mg) x 100] of 
ARRY-382 or if they did not receive pembrolizumab for any reason other than an AE or 
abnormal laboratory value that is not related to disease, disease progression, intercurrent illness 
or concomitant medications/therapies before completing Cycle 1. 
Dose modifications of study drug are described in Section 6.3. 
For Part A, after the last patient in a given cohort has completed 1 cycle of study treatment, the 
Sponsor Medical Monitor and Investigators will meet to review all safety data and decide 
whether to continue or halt dose escalation, expand individual dose levels to gain additional 
safety data, determine the MTD and/or RP2D, or explore other dose levels. In addition to end-of 
cohort meetings, safety meetings including the Sponsor Medical Monitor and Investigators will 
be scheduled periodically (e.g., every 4 weeks) during the conduct of Phase 2 to review safety 
data for ongoing patients and patients who are being monitored during the follow-up period. 
4.3 
End of Study 
End of study will be defined as the point when all patients have had the opportunity to be 
followed for at least 1 year after the date the last patient enrolled receives first treatment. Any 
patients still receiving study drugs at the end of the study will be allowed to continue at the 
discretion of the Investigator and as long as none of the treatment discontinuation criteria are met 
(see Section 9.2). The Sponsor will notify all applicable regulatory agencies in accordance with 
local requirements when the study has ended. After the end of the study, access to study drugs 
will be provided only in accordance with local regulations and requirements. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
72 
Confidential 
24 July 2018 
5.0 
PATIENT POPULATION 
This clinical study can fulfill its objectives only if appropriate patients are enrolled. The 
eligibility criteria described in this study protocol are designed to identify patients for whom 
treatment is considered appropriate. All relevant medical and nonmedical conditions should be 
considered when deciding whether a patient is suitable for enrollment in the study. 
5.1 
Number of Patients 
Overall, approximately 90 patients at approximately 30 study sites are planned for enrollment. 
Part A (Phase 1b) will consist of approximately 18 patients with selected solid tumors.  
The Phase 2 PD-1/PD-L1 Inhibitor Refractory cohort will consist of up to 20 patients with 
advanced solid tumors who progressed on a PD-1/PD-L1 inhibitor-containing regimen as their 
most recent prior line of therapy. If clinical activity is observed, enrollment may be focused to 
include up to 10 additional patients with particular tumor histologies of interest. 
The Phase 2 prOVCA cohort will consist of approximately 23 patients with prOVCA who are 
naïve to prior CPI therapy. The Phase 2 PDA cohort will consist of approximately 29 patients 
with PDA who have had at least one prior therapy who are naïve to prior CPI therapy.  
5.2 
Selection of Patients 
Questions regarding patient eligibility should be addressed with the Sponsor prior to enrollment 
of a particular patient. Patients must fulfill all of the following inclusion criteria and none of the 
exclusion criteria to be eligible for admission to the study. 
5.2.1 
Inclusion Criteria  
1. Personally signed and dated informed consent form 
2. Male or female ≥ 18 years of age 
3. Diagnosis of cancer that has been histologically or cytologically confirmed as follows: 
Part A (1 of the following): 
a. Ovarian cancer, triple-negative breast cancer, HNSCC, bladder cancer, metastatic 
CRC, PDA, or gastric cancer that is measurable or evaluable, nonmeasurable as 
defined by RECIST v1.1 and meets 1 of the following criteria:  
 is refractory to standard of care 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
73 
Confidential 
24 July 2018 
 no standard therapy available 
 patient refuses standard therapy  
b. Advanced, unresectable, or metastatic melanoma with or without prior treatment and 
measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1 
c. Advanced/metastatic PD-L1–positive NSCLC (defined as TPS ≥ 50%) with 
measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1 (1 of the 
following): 
 1) Patients with metastatic PD-L1 positive NSCLC with no EGFR or ALK 
genomic tumor aberrations and no prior systemic chemotherapy 
 2) Patients with advanced/metastatic PD-L1 positive NSCLC with disease 
progression on or after platinum-containing chemotherapy  
 3) Patients with advanced/metastatic PD-L1 positive NSCLC with EGFR or ALK 
genomic tumor aberrations, with disease progression on FDA-approved therapy 
for these aberrations 
All patients with NSCLC must provide documentation of positive PD-L1 
expression, defined as a TPS ≥ 50% on a fresh tumor biopsy (preferred) or the 
most recent archived tumor sample available. If test results documenting positive 
PD-L1 expression were not obtained using an FDA-approved test, then tumor 
tissue must be submitted to a central laboratory and it will be tested 
retrospectively using an FDA-approved test at a central laboratory (please see the 
laboratory manual for additional details). 
Phase 2 (1 of the following): 
a. Advanced/metastatic solid tumor with PD as defined by RECIST 1.1 or irRC on an 
anti-PD-1- or anti-PD-L1-containing regimen as their most recent prior therapy 
b. Advanced/metastatic epithelial ovarian cancer, peritoneal cancer or tubal cancer with 
measurable disease as defined by RECIST 1.1, that had progressed within 6 months 
of completing ≥ 4 cycles of platinum-based therapy 
c. Advanced/metastatic PDA that is locally advanced, unresectable or metastatic with 
measurable disease as defined by RECIST v1.1 in patients who have received at least 
one prior line of systemic therapy for their disease 
4. Eastern Cooperative Oncology Group Performance Status of 0 or 1 (see APPENDIX 1) 
5. Adequate bone marrow function at screening, characterized by the following: 
a. absolute neutrophil count (ANC) ≥ 1.0 × 109/L 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
74 
Confidential 
24 July 2018 
b. platelets ≥ 75 × 109/L 
c. hemoglobin ≥ 9.0 g/dL 
Note: Transfusions will be allowed to achieve the acceptable hemoglobin value. 
6. Adequate renal function characterized by serum creatinine ≤ 1.5 × upper limit of normal 
(ULN) or calculated or directly measured creatinine clearance ≥ 50 mL/min at screening 
7. Adequate hepatic function at screening, characterized by the following: 
a. serum total bilirubin ≤ 1.5 × ULN and < 2 mg/dL 
Note: Patients who have a total bilirubin level > 1.5 × ULN will be allowed if their 
indirect bilirubin level is ≤ 1.5 × ULN 
b. ALT and/or AST ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases 
8. For male patients and female patients of childbearing potential, agreement to use an 
acceptable method of contraception as defined in the protocol (see Section 5.3) from the 
start of study treatment until 7.5 months after the last dose of pembrolizumab for males 
and until 5.5 months after the last dose of pembrolizumab for females  
Note: Women are considered not of childbearing potential if they have had 12 months of 
natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age 
appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy 
with hysterectomy or tubal ligation at least 6 weeks prior to Screening. In the case of 
oophorectomy alone, only when the reproductive status of the woman has been 
confirmed by follow-up hormone level assessment is she considered not of childbearing 
potential. 
9. For females of childbearing potential only, negative serum human chorionic gonadotropin 
(hCG) pregnancy test result at baseline and nonlactating  
10. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, 
and other study procedures 
11. Phase 2 only: Availability of a fresh biopsy (preferred) or an archival tumor sample from 
the most recent sample available. Between 10 to 15 slides or an archival block are 
required. 
This requirement may be waived under certain circumstances (e.g., sufficient archived 
tissue is no longer available and fresh specimen collection is deemed medically unsafe or 
not feasible by the Investigator due to the location of the tumor) after discussion and 
agreement between the Sponsor and the Investigator. 


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5.2.2 
Exclusion Criteria 
Patients meeting any of the following criteria are ineligible for enrollment in the study. 
1. Prior treatment as follows: 
Part A:  
• An immune CPI (e.g., PD-1, PD-L1, or CTLA-4 inhibitor) 
NOTE: Prior treatment with a CSF-1R or CSF-1 (or macrophage colony-
stimulating factor [MCSF]) inhibitor is allowed. For patients with melanoma, 
prior treatment with ipilimumab is allowed if it was administered as adjuvant 
therapy and treatment was completed at least 3 months prior to enrollment. 
Phase 2:  
• A CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor   
• prOVCA and PDA patients only: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4 
inhibitor) 
2. Symptomatic brain metastasis at screening 
NOTE: Patients who are asymptomatic will be allowed, regardless of whether they 
received previous treatment for the metastases. Any brain metastases present at screening 
must be stable by imaging (e.g., magnetic resonance imaging [MRI] or computed 
tomography [CT]) demonstrating no evidence of progression at screening; patients must 
not be receiving anticonvulsant therapy and must have completed treatment with 
corticosteroids or be taking a decreasing dose of corticosteroids. 
3. Active autoimmune disease, documented history of autoimmune syndrome or disease, or 
a chronic medical condition that requires chronic steroid therapy or immunosuppressive 
medication 
NOTE: Exceptions include patients with vitiligo, resolved childhood asthma/atopy, 
patients who require intermittent use of bronchodilators or local steroid injections, and 
patients with a history of hypothyroidism taking a stable dose of replacement therapy. In 
addition, patients requiring physiological replacement doses of hydrocortisone or its 
equivalent (i.e., up to 20 mg hydrocortisone [or 5 mg prednisone] in the morning, and 
10 mg hydrocortisone [or 2.5 mg prednisone] in the evening) will be considered eligible 
for the study.  
4. Impaired gastrointestinal function or disease that may significantly alter the absorption of 
ARRY-382 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, 
malabsorption syndrome, small bowel resection) 


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5. Presence of risk factors for bowel obstruction or bowel perforation (e.g., history of acute 
diverticulitis, intra-abdominal abscesses, or abdominal carcinomatosis) 
6. History of severe hypersensitivity to mAb 
7. Active infection requiring therapy 
8. History of pneumonitis or interstitial lung disease 
9. Symptomatic ascites or symptomatic pleural effusion   
NOTE: For prOVCA patients, paracentesis or pleurocentesis to relieve symptoms prior to 
and during treatment will be permitted.   
10. Leptomeningeal disease 
11. Ocular melanoma 
12. Use of herbal medications/supplements or any medications or foods that are strong 
inhibitors or inducers of CYP3A4/5 within 2 weeks before the start of study treatment 
13. Clinically significant cardiac disease, including any of the following: 
a. congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2) 
b. uncontrolled hypertension per World Health Organization (WHO)/International 
Society of Hypertension (ISH) 2003 guidelines 
c. presence of clinically significant and uncontrolled atrial fibrillation 
d. unstable angina pectoris ≤ 3 months prior to enrollment 
e. acute myocardial infarction ≤ 3 months prior to enrollment 
14. QT abnormality or risk of QT abnormality, as follows:  
a. a prolonged QTcF ≥ 450 msec at screening (based on average of 3 readings) 
b. history or evidence of congenital long QT syndrome 
c. use of concomitant medications that may prolong QT/QTc interval or induce torsades 
de pointes (see APPENDIX 2) within 2 weeks before the start of study treatment 
15. Impaired hepatic function, defined as Child Pugh (Schwartz et al 2007) Class B or C 
(see APPENDIX 3) 


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16. Previous tumor malignancy within the last 3 years, or has a concurrent malignancy, with 
the exception of adequately treated basal cell or squamous cell carcinoma, in situ 
carcinoma of the cervix, in situ breast cancer, or in situ prostate cancer without evidence 
of active disease for 2 years before enrollment 
17. History of thromboembolic or cerebrovascular events, including transient ischemic 
attacks, cerebrovascular accidents, deep vein thrombosis, or pulmonary emboli within 
6 months before enrollment 
18. Prior therapy consisting of any of the following: 
a. cyclical chemotherapy within a period of time that was shorter than the cycle length 
used for that treatment (e.g., 6 weeks for nitrosourea, mitomycin-C)  
b. biologic therapy (e.g., antibodies), continuous or intermittent small-molecule 
therapeutics, or any other investigational agents within a period of time that is 
≤ 5 half-lives (t1/2) or ≤ 2 weeks (whichever is shorter)  
19. Residual Common Terminology Criteria for Adverse Events (CTCAE) ≥ Grade 2 side 
effects of any prior therapy, with the exception of residual Grade 2 alopecia 
20. Known history of human immunodeficiency virus (HIV) infection 
21. Active hepatitis B (hepatitis B surface antigen-[HBsAg-]reactive) or hepatitis C serology 
infection (hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] will be required if 
serology is positive) 
22. Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation or study drug administration or 
that may interfere with the interpretation of study results and, in the judgment of the 
Investigator, would make the patient an inappropriate candidate for the study 
5.3 
Contraception 
Female patients of childbearing potential must agree to use acceptable or highly effective 
methods of contraception to avoid pregnancy for the duration of study treatment through 
5.5 months after the last dose of pembrolizumab (i.e., 30 days [duration of ovulatory cycle] plus 
the time required for the investigational drug to undergo approximately 5 half-lives).  
Non-sterile male patients who are sexually active with female partners of childbearing potential 
must agree to use acceptable or highly effective methods of contraception to avoid fathering a 
child for the duration of study treatment and for 7.5 months after the last dose of pembrolizumab 


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(i.e., 90 days [duration of sperm turnover] plus the time required for the investigational drug to 
undergo approximately 5 half-lives). 
The permitted contraceptive methods listed below (CTFG Guidelines 2014) should be 
communicated to the patients and their understanding confirmed. 
The following methods have been determined to be highly effective (i.e., can achieve a failure 
rate < 1% per year when used consistently and correctly): 
• Complete abstinence from heterosexual intercourse during the entire period of risk 
associated with the study treatments; the reliability of sexual abstinence should be 
evaluated in relation to the duration of the clinical trial and the preferred and usual 
lifestyle of the patient 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o Oral 
o Intravaginal 
o Transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o Oral 
o Injectable 
o Implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomized partner (considered highly effective provided the vasectomized male has 
received medical assessment of surgical success and that the male is a female patient’s 
sole sexual partner) 
Acceptable birth control methods that result in a failure rate of more than 1% per year include: 
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 
• Male or female condom with or without spermicide 
• Cap, diaphragm or sponge with spermicide 


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6.0 
STUDY TREATMENT AND CONCOMITANT MEDICATIONS 
The term “study treatment” is defined as ARRY-382 or pembrolizumab. 
6.1 
Study Treatment Supplies 
6.1.1 
Manufacturing and Formulation 
ARRY-382 is manufactured by Avista Pharma Solutions and supplied by the Sponsor as powder 
in a capsule. Drug product will be provided in Swedish orange opaque size “00” (100 mg) 
gelatin capsules.  
Pembrolizumab is marketed in the United States by Merck, Sharp & Dohme Corp., a subsidiary 
of Merck & Co., Inc. (Whitehouse, NJ) in 2 formulations. Keytruda® (pembrolizumab) for 
injection, for iv use is supplied as 50 mg lyophilized powder in a single-use vial for 
reconstitution, and Keytruda® (pembrolizumab) injection, for iv use is supplied as 100 mg/4 mL 
(25 mg/mL) solution in a single-use vial.  
Pembrolizumab is marketed by Merck Sharp & Dohme Limited (Hoddesdon, UK) in the 
European Union in 2 formulations. Keytruda® (pembrolizumab) for injection, for iv use is 
supplied as 50 mg lyophilized powder for concentrate for solution for infusion in a single-use 
vial, and Keytruda® (pembrolizumab) injection, for iv use is supplied as 100 mg/4 mL 
(25 mg/mL) solution in a single-use vial. 
6.1.2 
Packaging and Labeling 
ARRY-382 capsules are packaged in high density polyethylene bottles with child-resistant 
plastic caps and safety-seal features and sent to the site in bulk. Label content will include, at a 
minimum, the lot number, storage information, and a statement that the contents are 
investigational in nature. Each bottle will be labeled in compliance with local regulations. 
Commercially available pembrolizumab will be used in this study according to local regulations 
in each participating country. Pembrolizumab for injection (lyophilized powder) and 
pembrolizumab injection (solution) is packaged in individual cartons containing single-use vials. 
Pembrolizumab will be supplied either locally or by the Sponsor. Pembrolizumab preparation 
must be in accordance with the label and with local institutional guidelines. The Sponsor, or 
designee, will provide each site with the most current local pembrolizumab Prescribing 
Information and distribute any updates as they become available (see also Section 6.3.3). 


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6.1.3 
Shipping, Storage and Handling 
Labeled, packaged study drug will be shipped to each study site by the Sponsor or designee 
following receipt of the necessary regulatory documents. The Investigator or an approved 
representative (e.g., registered pharmacist) will ensure that all study drug is stored as outlined in 
the Pharmacy Manual and in accordance with applicable regulatory requirements. The drug 
storage area at the site must be secure, with access limited to authorized personnel. 
Stability studies to support drug storage conditions have been conducted by the Manufacturer or 
an affiliate. The Manufacturer will continue to monitor the stability of the study drug and the 
Sponsor will alert the site if a lot is nearing the end of its anticipated shelf life. 
ARRY-382 capsules are to be stored at controlled room temperature (15°C to 30°C). Detailed 
instructions for storage and handling of investigational product will be provided in the Pharmacy 
Manual. 
Pembrolizumab for injection (lyophilized powder) is to be stored under refrigeration at 2°C to 
8°C (36°F to 46°F). Pembrolizumab injection (solution) is to be stored under refrigeration at 2°C 
to 8°C (36°F to 46°F) in the original carton to protect it from light.  
6.1.4 
Accountability and Return of Study Drug Supply 
The Investigator or an approved representative (e.g., pharmacist) must maintain accurate records 
of dates and quantities of study drug received, to whom study drug is dispensed 
(patient-by-patient accounting), and accounts of any study drug accidentally or deliberately 
destroyed. The Investigator must retain all unused or expired study drug supplies until the study 
monitor has confirmed the accountability data. If a study site’s policy prohibits holding study 
drug supplies for monitor review, then a copy of the standard operating procedure (SOP) for 
processing drug returns must be provided to the Sponsor. 
To ensure adequate records, all study drug will be accounted for on a drug accountability 
inventory form as instructed by the Sponsor. Instructions for processing all unused or expired 
study supplies will be included in the Pharmacy Manual. 
6.2 
Study Drug Dispensing and Administration 
6.2.1 
ARRY-382 
ARRY-382 oral capsules will be administered QD (approximately 24 ±2 hours) as a fixed dose 
either without food or after a light meal (e.g., breakfast) with approximately 240 mL of water. 
ARRY-382 should not be taken within 4 hours after a full meal because preliminary results 


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suggest a modest increase in exposure with larger meals (Section 2.2.2.2). Patients will be 
instructed not to crush study drug capsules.  
The pharmacist or study nurse will ensure that the appropriate dosage is dispensed and will 
provide the patient with at least the appropriate number of capsules for the number of doses to be 
taken prior to the next scheduled visit.  
Study site personnel will train the patient and/or the patient’s caregiver on dosing procedures for 
the study drug. Patients will receive a diary to document self-administered dosing of study drug 
in each cycle to include the dose of study drug taken, the date and timing of dosing, if any doses 
were missed and the reason for the missed dose, and timing and type of meals eaten in relation to 
dosing. One diary will be provided per cycle. Patients will be instructed to return unused study 
drug and the patient diary to the site at each visit. 
Complete dispensing instructions, dosing instructions (including the timing of study drug 
administration), dosing in relation to meals and instructions for missed doses will be provided in 
the Pharmacy Manual. 
6.2.1.1 
Part A 
Patients with selected solid tumors in Part A will receive oral doses of single-agent ARRY-382 
capsules in combination with pembrolizumab. Planned dose levels of ARRY-382 are 200 mg QD 
and 400 mg QD; the dose escalation scheme is described in Section 4.1. 
6.2.1.2 
Phase 2 
Patients in the Phase 2 cohorts (PD-1/PD-L1 Inhibitor Refractory, prOVCA and PDA) will 
receive oral doses of ARRY-382 capsules at 300 mg QD, the MTD/RP2D determined during 
Part A, in combination with pembrolizumab. 
6.2.2 
Pembrolizumab 
For Part A: Pembrolizumab 2 mg/kg will be administered by study site personnel as an iv 
infusion over 30 minutes Q3W. The initial patient dose will be based on baseline body weight 
determined by the pharmacist. Dosing will be updated throughout the study based on body 
weight on Day 1 of each cycle or at a frequency determined by local practices. 
For Phase 2: Pembrolizumab will be dosed at 200 mg and will be administered by study site 
personnel as an iv infusion over 30 minutes (within -5 to +10 minutes) Q3W. 


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6.3 
Dose Modifications and Reductions 
Doses of ARRY-382 and pembrolizumab may be modified throughout the study. 
Cycle 1 Day 1 is defined as the first day of study drug treatment with both ARRY-382 and 
pembrolizumab. Per the schedule of events, cycles are defined as 21 days and pembrolizumab 
should be administered Q3W. In the event of temporary dose interruptions, the re-start of 
subsequent cycles may correspond with administration of either ARRY-382 or pembrolizumab. 
Doses of ARRY-382 withheld during a cycle will not be made up. 
6.3.1 
General Guidelines  
If assessment of the toxicity can be clearly attributed to ARRY-382 or pembrolizumab, 
administration of the offending drug should be interrupted and the toxicity should be followed 
until resolution or return to baseline according to the respective dose modification guidelines 
described in Sections 6.3.2 and 6.3.3. Treatment with the other agent in the combination may 
continue without alterations. 
If attribution of the toxicity cannot be clearly ascribed to either ARRY-382 or pembrolizumab, 
then both agents should be stopped and the toxicity should be followed until resolution or return 
to baseline. For patients with melanoma, long-term single-agent treatment with ARRY-382 is not 
recommended; if pembrolizumab is permanently discontinued for these patients, ARRY-382 
may also be discontinued. In special circumstances, if a patient is benefitting from therapy, that 
patient may continue to receive single-agent ARRY-382 after discussion with the Sponsor. 
If the toxicity recurs after a dose reduction, the process outlined above should be followed once 
again to determine attribution to either study drug or both study drugs.  
6.3.2 
ARRY-382 
General guidelines for dose modifications of ARRY-382 are provided in Table 8. However, 
Investigators are to use their judgment when assessing the clinical significance of individual 
AEs. 


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Table 8: 
Recommended Dose Modifications for ARRY-382 Treatment-Related 
Adverse Events 
Severity of Event 
Action to be Taken 
Grade 0-1 
• Maintain ARRY-382 dose level and provide treatment to control symptoms, if applicable. 
Grade 2 
• Provide treatment to control symptoms, if applicable. If the symptoms cannot be controlled, 
withhold ARRY-382 until resolution or return to baseline. Then, resume at the original dose. 
• In the event of a persistent Grade 2 AE that is not responsive to treatment measures or that 
prevents the patient from resuming treatment, ARRY-382 treatment may be resumed at the 
next lower dose level. 
• In the event of irAEs: 
o 
At first occurrence, withhold ARRY-382 until resolution or return to baseline. Then, 
resume treatment with ARRY-382 at the same dose level. 
o 
At second occurrence, withhold ARRY-382 until resolution or return to baseline. Then 
resume treatment with ARRY-382 at the next lower dose level. 
o 
At third occurrence, discontinue ARRY-382. 
Grade 3 
• Withhold ARRY-382 until the AE recovers to resolution, or return to baseline. Then, resume 
treatment with ARRY-382 at the next lower dose level.a 
• In the event of a Grade 3 QTcF prolongation or > 60 msec increase in QTcF interval seen on  
≥ 2 ECGs (on at least 2 separate ECGs). 
o 
At first occurrence, interrupt ARRY-382 until QTcF decreases below 500 msec. Then 
resume treatment at next lower dose level 
o 
At second occurrence, discontinue ARRY-382. 
Grade 4 
• Discontinue administration of ARRY-382b 
Dose delay 
> 21 days due to 
AEs and not 
underlying disease 
progression, 
concomitant 
illness, or non-
medical issues 
• Discontinue administration of ARRY-382 (unless it is in the best interest of the patient to 
continue treatment, as judged by the Investigator) 
ALT or AST 
elevations  
• ALT or AST > 8 × ULN ≤ 20 × ULN (Grade 3) 
o 
Withhold ARRY-382. Resume treatment at the next lower dose level if ALT or AST 
resolves to Grade 1 or baseline (or ≤ 5 × ULN in presence of liver metastases) in  
≤ 7 days 
o 
Discontinue ARRY-382 if ALT or AST > 8 × ULN for > 7 days   
• ALT or AST ≥ 5 × ULN and ≤ 8 × ULN (Grade 3) 
o 
Withhold ARRY-382. Resume treatment at the next lower dose level if ALT or AST 
resolves to Grade 1 or baseline in ≤ 14 days 
o 
Discontinue ARRY-382 if ALT or AST > 5 × ULN for > 14 days 
• ALT or AST > 3 × ULN and bilirubin levels ≥ 2 × ULN or an INR > 1.5 unless clearly 
attributable to disease progression  
o 
Discontinue ARRY-382 
• ALT or AST >20 × ULN (Grade 4) 
o 
Discontinue ARRY-382 


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AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CK = creatine kinase; ECG = 
electrocardiogram; INR = international normalized ratio; irAE = immune-related adverse event; QTcF = QT interval corrected for heart 
rate using Fridericia’s formula; ULN = upper limit of normal 
a The following exceptions apply: 1) ARRY-382 should not be withheld for increased CK unless it is associated with an increase in 
creatinine ≥ 1.5 × the baseline value for creatinine OR until the CK increase remains ≥ Grade 3 for > 7 days. 2) In the event of 
Grade 3 nausea, vomiting or diarrhea, the patient can continue at the same dose of ARRY-382 if the patient is responsive to treatment 
measures. 
b A patient with a Grade 4 AE may resume treatment at the next lower dose level if the AE recovers to Grade 0 or 1 and, if in the 
opinion of the Investigator and Sponsor, the patient can be monitored for recurrence of AE. 
 
Patients should be evaluated weekly, at a minimum for nonlaboratory, ARRY-382-related 
toxicities until resolution or return to baseline, and then at least monthly until return to baseline, 
whichever comes first. For abnormal laboratory values that qualify as AEs, patients should be 
followed twice weekly until resolution or return to baseline.  
Doses of ARRY-382 withheld during a cycle will not be made up. When a dose reduction is 
required because of AEs, no dose re-escalation will be permitted for the duration of study 
treatment.  
For ARRY-382 dose modifications or reductions because of AEs in patients enrolled in Part A of 
the study, please refer to Table 6 in Section 4.1. Only 2 dose reductions (in 100 mg increments) 
are allowed in all patients in any study part/phase with 100 mg QD as the lowest possible dose. 
6.3.3 
Pembrolizumab 
Pembrolizumab belongs to a class of cancer therapies commonly referred to as immune 
checkpoint inhibitors. Despite important clinical benefits, checkpoint inhibition is associated 
with a unique spectrum of side effects termed immune-related adverse events (irAEs) or, 
occasionally, AEs of special interest (Naidoo et al 2015; Champiat et al 2016). IrAEs include 
dermatologic, gastrointestinal, hepatic, endocrine, and other less common inflammatory events. 
IrAEs are believed to arise from general immunologic enhancement, and temporary 
immunosuppression with corticosteroids, tumor necrosis factor-alpha antagonists, 
mycophenolate mofetil, or other agents can be an effective treatment in most cases.  
In general, treatment of moderate or severe requires interruption of the checkpoint inhibitor and 
the use of corticosteroid immunosuppression. Patients should be carefully monitored during 
treatment for initial evidence of Grade 1 AEs. Treatment is based upon the severity of the 
observed toxicity.  
Instructions for monitoring and treating irAEs associated with pembrolizumab are described 
fully in the most current local Prescribing Information for Keytruda® (pembrolizumab). The 
Sponsor, or designee, will ensure that each site will be provided with the most current local 


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Prescribing Information for pembrolizumab. The Sponsor will notify applicable sites and 
distribute updated information as it is approved and becomes available in each country. 
Investigators should apply the guidelines within this document to treat patients experiencing an 
irAE(s) suspected to be due to pembrolizumab. These instructions include when and for how 
long to withhold pembrolizumab, when to reduce the dose of pembrolizumab and when 
pembrolizumab must be discontinued. If the Investigator has any questions on how to proceed 
with patient treatment for a pembrolizumab-associated irAE following review of the most current 
local pembrolizumab Prescribing Information, the Investigator should consult with their local 
medical monitor and/or the Sponsor.  
6.4 
Treatment Compliance 
Compliance will be evaluated at each visit by a review of patient diary entries, an accounting of 
returned drug product, and patient interviews. 
6.5 
Prior and Concomitant Medications 
6.5.1 
Prior Treatments 
All prior cancer treatments are to be recorded in the electronic case report form (eCRF). Other 
prior treatments (i.e., other than cancer treatments) taken within 4 weeks of screening should also 
be recorded. 
6.5.2 
Concomitant Medications 
Unless specifically prohibited, concomitant medications can be administered at the Investigator’s 
discretion to conform to standard practice during the treatment period. All concomitant 
medications are to be recorded on the eCRF using generic drug names when possible. 
Antacids should be taken approximately 4 hours after administration of ARRY-382. The aqueous 
solubility of ARRY-382 is pH-dependent. Therefore, antacid medications (including proton 
pump inhibitors such as omeprazole, lansoprazole or esomeprazole) may decrease the absorption 
of ARRY-382. 
Moderate or weak CYP3A4 inhibitors and inducers, and P-gp inhibitors and substrates should be 
used with caution as they may affect the clearance of ARRY-382 (see APPENDIX 4). 
ARRY-382 is not a potent inhibitor or inducer of human CYP enzymes in isolated enzyme 
systems and its probability to interact with other medications that are substrates of CYP 
metabolism is expected to be low. However, Investigators should use normal caution when 
prescribing concomitant medications, as with any novel therapeutic for which there is limited 
clinical experience. 


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Investigators should contact the Sponsor when they are unsure whether a drug should be 
prescribed to a patient in the clinical study.  
6.5.3 
Prohibited Medications 
The following therapies are prohibited during the study (unless otherwise noted): 
• Chronic steroid therapy or immunosuppressive medication 
Note: Physiological replacement doses of hydrocortisone or its equivalent (i.e., up to 
20 mg hydrocortisone [or 5 mg prednisone] in the morning and 10 mg hydrocortisone [or 
2.5 mg prednisone] in the evening) will be allowed. 
• Medications that may prolong the QT/QTc interval or induce torsades de pointes (see 
APPENDIX 2). 
• Strong inhibitors or inducers of CYP3A  
In vitro drug metabolism studies suggest that ARRY-382 is a substrate of CYP3A and its 
systemic exposure may be affected by medications that are strong CYP3A inhibitors and 
inducers. Known strong inhibitors of CYP3A include, but are not limited to, 
ketoconazole, itraconazole, clarithromycin, erythromycin, grapefruit juice, 
troleandomycin, diltiazem, fluoxetine, and verapamil. Known inducers of CYP3A 
include, but are not limited to, rifampicin, phenytoin, carbamazepine, barbiturates, and 
St. John’s Wort. For a more complete list of strong CYP3A inhibitors and inducers, see 
APPENDIX 2.  
• Anticancer agents (e.g., cytotoxic chemotherapy, small-molecule targeted agents, 
biological agents, immune response modifiers or hormonal therapy)  
• Herbal remedies 
• Investigational drugs and devices 
• Consult the most current local pembrolizumab Prescribing Information for possible other 
prohibited medications  


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7.0 
STUDY PROCEDURES AND ASSESSMENTS 
The procedures and assessments that will be conducted during this study are described in this 
section in narrative form, described by study visit in Section 8.0, and summarized in Table 10 
and Table 11. 
Written informed consent must be granted by each patient prior to the initiation of any study 
procedure or assessment (other than those considered standard of care). 
7.1 
Screening and Continued Eligibility Tests 
7.1.1 
Medical History/Disease History 
Significant (at the Investigator’s discretion) past and present medical history, including alcohol 
and nicotine history over the 3 months before screening, will be recorded. Any ongoing 
condition observed prior to the initiation of study treatment will be recorded. 
Document cancer diagnosis, molecular alterations and extent of disease (i.e., stage at diagnosis 
and at study start and any previously determined biomarker data including germline or somatic 
mutation status, MSI status/MMR proficiency, tumor mutation burden level, PD-L1 status or any 
disease-specific gene expression subtype). 
7.1.2 
Pregnancy Tests 
All females of childbearing potential are required to have a serum pregnancy test at Screening; 
serum or urine pregnancy tests will be allowed at subsequent time points specified in Table 10 
and Table 11. Any positive test result will result in immediate cessation of study drug 
administration. 
Patients of nonchildbearing potential do not require pregnancy tests. Women are considered not 
of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with 
an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have 
had surgical bilateral oophorectomy with hysterectomy or tubal ligation at least 6 weeks prior to 
Screening. In the case of oophorectomy alone, only when the reproductive status of the woman 
has been confirmed by follow-up hormone level assessment is she considered not of childbearing 
potential. 
All blood or urine collections for pregnancy tests occurring on dosing days must be performed 
prior to study drug administration. 


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7.1.3 
Hepatitis Tests 
Blood samples for testing of hepatitis B virus (HBV; HBsAg-reactive) and HCV serology (HCV 
RNA [qualitative] will be required if serology is positive) will be collected at screening. 
7.1.4 
Local and Retrospective Testing for PD-L1 Expression (Part A Patients with 
Non-Small Cell Lung Carcinoma Only) 
Patients with NSCLC in Part A must have documentation of positive PD-L1 expression to be 
eligible for participation in the study. Testing should be performed locally on a fresh tumor 
biopsy (preferred) or the most recent archived tumor sample available. Instructions for obtaining 
the tissue sample will be provided in the Laboratory Manual. 
If tests results documenting positive PD-L1 expression were not obtained using an 
FDA-approved test, then tumor tissue will be tested retrospectively using an FDA-approved test 
at a central laboratory. 
7.1.5 
Tumor and Blood Samples for Retrospective Testing of Tumor Genomic 
Alterations, Tumor Mutation Burden and/or Gene Expression Profiling (Phase 2 
Only) 
Patients in Phase 2 must have a fresh biopsy (preferred) or an archival tumor sample from the 
most recent sample available submitted to be eligible for participation in the study. This 
requirement may be waived under certain circumstances (e.g., sufficient archived tissue is no 
longer available and fresh specimen collection is deemed medically unsafe or not feasible by the 
Investigator due to the location of the tumor) after discussion and agreement between the 
Sponsor and the Investigator. 
All patients in Phase 2 will have PD-L1 expression, tumor genomic alterations including 
microsatellite instability (MSI) status/MMR proficiency, tumor mutation burden and/or gene 
expression profiling obtained from patient records when available and will be confirmed by 
retrospective testing of the fresh or archived tumor specimen plus a blood sample at a central 
laboratory.  
Information regarding tissue specimen requirements, preparation and shipment of tumor blocks 
or slides, and sample handling will be provided in the Laboratory Manual. 
7.2 
Efficacy Assessments 
Tumor assessments will include imaging (e.g., CT, MRI, x-ray, fluorodeoxyglucose positron 
emission tomography [FDG-PET]) and caliper measurements, as applicable, and will be 
performed at the time points specified in Table 10 and Table 11.  


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
91 
Confidential 
24 July 2018 
If a patient experiences an AE that results in an unscheduled visit or meets SAE criteria, a blood 
sample for measurement of plasma concentrations of ARRY-382 and its metabolites 
(AR00469099, AR00469100, and AR00470870) should be collected if less than 24 hours has 
elapsed since the last dose of study drug, if possible. 
If vomiting occurs within 4 hours following study drug administration on the day of PK blood 
sampling, the time (using the 24-hour clock) of vomiting should be recorded on the transmittal 
forms that accompany the sample and that dose of study drug should not be re-administered. 
7.5 
Safety Assessments 
7.5.1 
Adverse Events 
Adverse events will be assessed by direct observation and patient interviews. Patients should be 
questioned using non-leading questions. Assessment and reporting of AEs is described in detail 
in Section 10.0 and will be completed at the time points specified in Table 10 and Table 11. 
7.5.2 
Clinical Laboratory Tests 
Clinical laboratory tests include hematology, coagulation, clinical chemistry, thyroid panel, and 
urinalysis (Table 9) and will be collected at the time points specified in Table 10 and Table 11. It 
is expected that local laboratories will be used for all protocol-specified and unscheduled 
laboratory tests related to safety. Depending on the availability of certain tests at local 
laboratories, some protocol-specified laboratory tests may be performed outside of local 
laboratories. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
92 
Confidential 
24 July 2018 
Table 9: 
Clinical Laboratory Tests 
Hematology 
Chemistry 
Urinalysis 
Others 
Hemoglobin 
Hematocrit 
RBC 
Platelets 
WBC 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
BUN 
Urea 
Uric acid  
Creatinine 
Creatinine clearancea 
Total protein 
Albumin 
Alkaline phosphatase 
AST 
ALT 
Lactate dehydrogenase 
Total bilirubin 
Indirect bilirubin 
Direct bilirubin (if total 
bilirubin values are above 
normal) 
Amylase 
Lipase 
Aldolase 
CK 
CK isoenzymesc 
Glucose 
Sodium 
Potassium 
Chloride 
Bicarbonate  
Calcium 
Magnesium 
Phosphorus 
Appearance 
Color 
Specific gravity 
pH 
Myoglobinc 
Protein 
Glucose 
Ketones 
Blood 
Nitrite 
Leukocyte esterase 
If urinalysis is abnormal, 
then microscopy: 
• WBC 
• RBC 
• Bacteria 
• Epithelial cells 
• Casts 
• HBsAg and HCV 
serology (RNA, 
qualitative if serology 
positive) (screening 
only) 
• Serum or urine 
pregnancy testb (females 
of childbearing potential 
only) 
Coagulation 
INR 
PT 
aPTT/PTT 
Thyroid Panel 
TSH 
T3, free 
T4, free 
ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; BUN = blood 
urea nitrogen; CK = creatine kinase; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; INR = International 
Normalized Ratio; PT = prothrombin time; PTT=partial thromboplastin time; RBC = red blood cells; RNA = ribonucleic acid; T3 
= triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; WBC = white blood cells 
a Creatinine clearance will be calculated using the Cockcroft-Gault formula [(140 – age)*body mass (kg) / creatinine 
(mg/dL)*72]*0.85 for females or 1.00 for males. 
b Serum pregnancy test required at screening only; serum or urine pregnancy tests will be allowed at subsequent time points. 
c Measurement of CK isoenzymes and urine myoglobin only necessary if total CK is ≥ Grade 2, unless there are cardiac signs 
and symptoms. If cardiac signs and symptoms are present, measure CK isoenzymes and urine myoglobin if total CK is any 
grade above normal. 
 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
93 
Confidential 
24 July 2018 
Site-specific handling instructions for hematology, coagulation, clinical chemistry, thyroid panel, 
and urinalysis samples should be followed. Screening results will be assessed by the Investigator 
to determine patient eligibility. Day 1 results (or assessments allowed within 96 hours prior to 
Day 1) will be assessed by the Investigator prior to first dose of study treatment; clinical 
chemistry and coagulation test results must be reviewed before the first dose of study drug is 
administered in each cycle. Additional clinical laboratory tests may be obtained at any time 
during the study at the Investigator’s discretion. Clinically significant findings should be 
followed to resolution or stabilization.  
Blood and urine sample collections on dosing days must be performed prior to study treatment 
administration. Laboratory test results required to make decisions regarding potential dose 
modifications (as specified in Section 6.3) should be reviewed prior to study treatment 
administration. 
7.5.3 
Physical Examination 
Physical examinations, including weight, will be performed by trained medical personnel at the 
time points specified in Table 10 and Table 11. Height will be measured only at screening. All 
physical examinations occurring on dosing days must be performed prior to study drug 
administration. 
7.5.4 
Vital Signs 
Vital signs (blood pressure, pulse, and temperature) will be measured per institutional standards 
at the time points specified in Table 10 and Table 11. Any treatment-emergent abnormal findings 
will be recorded as AEs. 
7.5.5 
Electrocardiogram 
Triplicate 12-lead ECGs will be performed at the time points specified in Table 10 and Table 11. 
At each measurement, 3 serial ECGs will be obtained over a period of approximately 5 to 
10 minutes. The mean of the triplicate ECG measurements performed at predose on Day 1 will 
serve as each patient’s baseline value for all postdose comparisons. 
In some cases, it may be appropriate to repeat an abnormal ECG. However, if the Investigator is 
able to interpret the ECG, then an abnormal ECG does not need to be repeated. When ECGs are 
to be performed at the same time point as a blood collection, ECGs should be performed first. 
QT interval values will be corrected using Fridericia’s formula (QTcF). 
All ECGs will be submitted for central assessment. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
94 
Confidential 
24 July 2018 
7.6 
Eastern Cooperative Oncology Group Performance Status 
Assessment of ECOG PS (APPENDIX 1) will be conducted at the time points specified in 
Table 10 and Table 11. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
95 
Confidential 
24 July 2018 
8.0 
SCHEDULE OF PROCEDURES AND ASSESSMENTS 
Before recruitment of patients into the study, written Ethics Committee (EC) approval of the 
protocol, informed consent, and any additional patient information must be obtained. 
During screening, the Sponsor will assign a unique number to each patient who provides written 
informed consent. Once a patient is in screening or is enrolled in the study, that patient will be 
identified only by the assigned patient number. 
The Investigator or designee is responsible for verifying that the patient is eligible before 
requesting registration.  
At the site, the Investigator will maintain a log for all screened patients (including patients who 
fail screening after providing written informed consent) and all enrolled patients. 
Patients should be treated within 5 working days of the registration/enrollment date. The 
registration/enrollment date is the date that the Sponsor assigns a patient to a given dose level. 
The procedures and assessments that will be conducted during this study are described in this 
section by study visit, described in narrative form in Section 7.0 and summarized in Table 10 and 
Table 11.  
Any patients enrolled in previous Part C/Phase 2 should follow the Phase 2 procedures and 
assessments (Section 8.2.2) and schedule of events (Table 11). 
8.1 
Screening Evaluations 
All screening procedures to determine eligibility must be performed within 28 days prior to the 
first dose of study treatment. Eligibility is determined by results of screening assessments 
performed prior to the first dose of study treatment and up to and including Cycle 1 Day 1. If a 
particular assessment is repeated, the results obtained closest to the first dose of study treatment 
should be used to assess eligibility. 
Within 28 days of Day 1 dosing: 
• Administration of written informed consent (must be obtained prior to performance of 
any study-specific tests or evaluations that are not considered standard of care) 
• Demographics 
• Medical history, including alcohol and nicotine use for the 3 months before screening, 
and disease history 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
96 
Confidential 
24 July 2018 
• Verification of eligibility criteria 
• Prior treatments, including all cancer treatments, and any other prior treatments (i.e., 
other than cancer treatments) taken within 4 weeks before screening 
• Confirmation of positive PD-L1 expression for patients with NSCLC in Part A. Prior 
documentation of TPS ≥ 50%, or fresh tumor biopsy or most recent archived tumor tissue 
sample for local testing for PD-L1 expression.  
Note: If test results documenting positive PD-L1 expression for purposes of determining 
eligibility were not obtained using an FDA-approved test, then tumor tissue will be tested 
retrospectively using an FDA-approved test at a central laboratory. 
• All patients in Phase 2: Obtain and send a fresh biopsy plus a blood sample, or the most 
recent archived tumor tissue sample available plus a blood sample to the central 
laboratory for testing of PD-L1 expression, MMR proficiency, tumor genomic alterations 
including MSI status and/or gene expression profiling. 
• Tumor assessments, i.e., imaging (e.g., CT, MRI, x-ray, FDG-PET) and caliper 
measurements, as applicable 
Within 14 days of Day 1 dosing: 
• ECOG PS 
• Physical exam, including body weight and height 
• Vital signs, including blood pressure, pulse, and temperature 
• Triplicate 12-lead ECG over a period of approximately 5 to 10 minutes 
• Blood samples for the following tests: 
o Serum pregnancy test (females of childbearing potential only) 
o Hepatitis testing (HBV and HCV) 
o Clinical chemistry, thyroid panel, hematology, and coagulation 
• Urine sample for urinalysis 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
100 
Confidential 
24 July 2018 
• Administration of pembrolizumab 
• Review of concomitant medications 
• Review of AEs 
8.2.1.2.2 
Subsequent Cycles Day 15 (± 2 Days)* 
• Blood sample for the clinical chemistry and hematology (Cycles 2, 3, and 4 only) 
• Administration/dispensing of ARRY-382 
• Review of concomitant medications 
• Review of AEs 
* For Cycles ≥ 5, on each Day 15 where only AEs and concomitant medications are 
assessed, a telephone call to the patient can substitute for a clinical visit. However, if the 
Investigator feels that there are AEs that need to be further assessed, a clinic visit may be 
warranted. 
8.2.2 
Phase 2 
8.2.2.1 
Cycle 1  
8.2.2.1.1 
Cycle 1 Day 1  
• Verification of eligibility criteria 
• Updates to prior treatments 
• ECOG PS (need not be repeated if performed within 96 hours before Cycle 1 Day 1) 
• Physical examination, including body weight (need not be repeated if performed within 
96 hours before Cycle 1 Day 1) 
• Vital signs, including blood pressure, pulse, and temperature  
• Triplicate 12-lead ECG over a period of approximately 5 to 10 minutes  
o Predose (need not be repeated if performed within 96 hours before Cycle 1 Day 1) 
and 4 hours postdose 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
105 
Confidential 
24 July 2018 
8.4 
30-Day (± 3 Days) Safety Follow-up Visit 
All patients will return for a 30-Day Safety Follow-up Visit approximately 30 days after the last 
dose of study treatment or prior to the initiation of subsequent anticancer therapy, whichever 
occurs first. 
• ECOG PS 
• Physical exam, including body weight  
• Vital signs, including blood pressure, pulse, and temperature 
• Serum or urine pregnancy test (females of childbearing potential only) 
• Blood sample for the following tests: 
o Clinical chemistry, thyroid panel, hematology, and coagulation  
• Urine sample for urinalysis 
• Review of AEs 
Additional safety assessments may be performed to monitor any safety concerns identified at the 
treatment discontinuation visit. If the treatment discontinuation visit was performed ≥ 21 days 
from last dose of study drug, the 30-day safety follow-up visit does not need to be performed. 
8.5 
Follow-up Visits for Disease Progression 
Tumor assessments are to be performed only if clinically indicated after the 30-day safety 
follow-up visit. Patients who discontinue study treatment for a reason other than disease 
progression should be encouraged to continue with tumor assessments every 8 weeks ± 1 week 
until disease progression as determined by the Investigator, withdrawal of consent, initiation of 
subsequent anticancer therapy, the patient is lost to follow-up, or death, whichever occurs first. 
8.6 
Monitoring for Survival Status 
After patients have completed all other follow-up visits (i.e., 30-day safety follow-up visit or 
follow-up visits for disease progression), they will be contacted via telephone or electronic 
means every 3 months (Q3M; ± 2 weeks) for survival status for 1 year after the date of the last 
patient’s first visit. During this follow-up period, any subsequent anticancer therapies should be 
recorded in the eCRF. 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
106 
Confidential 
24 July 2018 
8.7 
Collection of Data for Ongoing Patients Following Database Lock 
If the primary objective of the study has been met or the Sponsor decides to stop the study early, 
the database may be locked for the purpose of analyzing and reporting data. Patients may 
continue to receive study treatment per protocol beyond database lock if the Investigator and the 
Sponsor agree that patients’ best interests are served by continuing to receive study treatment. In 
patients who continue on study treatment, the Sponsor may decide to only follow for safety (i.e., 
collect only SAE information, not require any study-specific procedures, and mandate that 
patients be followed according to standard of care), where allowable per local laws or 
jurisdictions. 
 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
107 
Confidential 
24 July 2018 
Table 10: 
Schedule of Events (Part A/Phase 1b) 
 
 
Treatment 
 
 
 
Cycle 1 
Subsequent 
cycles 
 
Procedure or Assessment 
Screening 
Day  
Day  
Follow-up 
(–28 to  
–1) 
(–14 to 
–1) 
1 
 
8 
(± 1) 
15 
(± 1) 
1 
(± 2) 
15 
(± 2) 
Treatment 
Discontin-
uation  
(within 2 
weeks) 
30-day Safety 
(± 3 days)a 
For 
Progression
Q8W 
(± 1 week) 
For 
Survival 
Q3M  
(± 2 weeks) 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
Demographics  
x 
 
 
 
 
 
 
 
 
 
 
Medical historyb 
x 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
x 
 
x 
 
 
 
 
 
 
 
 
Prior treatmentsc 
x 
 
x 
 
 
 
 
 
 
 
 
ECOG PS 
 
x 
xd 
 
 
x 
 
x 
x 
 
 
Physical exam, including body weight 
 
xe 
xd 
 
 
x 
 
x 
x 
 
 
Vital signsf 
 
x 
x 
 
 
x 
 
x 
x 
 
 
Pregnancy testg 
 
x 
xd 
 
 
x 
 
x 
x 
 
 
Tumor biopsy/archived tumor tissue 
sample for PD-L1 expressionh 
x 
 
 
 
 
 
 
 
 
 
 
HBsAg, HCV RNA (qualitative) 
 
x 
 
 
 
 
 
 
 
 
 
Triplicate 12-lead ECGi 
 
x 
xd 
 
 
xj 
 
 
 
 
 
Single 12-lead ECG 
 
 
 
 
 
xk 
 
x 
 
 
 
Clinical chemistry 
 
x 
xd 
x 
x 
x 
xl 
x 
x 
 
 
Thyroid panel 
 
x 
xd 
 
 
x 
 
x 
x 
 
 
Hematology 
 
x 
xd 
x 
x 
x 
xl 
x 
x 
 
 
Coagulation 
 
x 
xd 
 
 
x 
 
x 
x 
 
 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
110 
Confidential 
24 July 2018 
Table 11: 
Schedule of Events (Phase 2) 
 
 
Treatment 
 
 
 
Cycle 1 
Subsequent 
cycles 
 
Procedure or Assessment 
Screening 
Day  
Day  
Follow-up 
(–28 to  
–1) 
(–14 to 
–1) 
1 
 
8 
(± 1) 
15 
(± 1) 
1 
(± 2) 
15 
(± 2) 
Treatment 
Discontin-
uation  
(within 2 
weeks) 
30-day Safety 
(± 3 days)a 
For 
Progression
Q8W 
(± 1 week) 
For 
Survival 
Q3M  
(± 2 weeks) 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
Demographics  
x 
 
 
 
 
 
 
 
 
 
 
Medical historyb / Disease history 
x 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
x 
 
x 
 
 
 
 
 
 
 
 
Prior treatmentsc 
x 
 
x 
 
 
 
 
 
 
 
 
ECOG PS 
 
x 
xd 
 
 
x 
 
x 
x 
 
 
Physical exam, including body weight 
 
xe 
xd 
 
 
x 
 
x 
x 
 
 
Vital signsf 
 
x 
x 
 
 
x 
 
x 
x 
 
 
Pregnancy testg 
 
x 
xd 
 
 
x 
 
x 
x 
 
 
Fresh tumor biopsy and blood sample or 
archived tumor tissue and blood 
sampleh 
x 
 
 
 
 
 
 
 
 
 
 
Hepatitis testing (HBV and HCV) 
 
x 
 
 
 
 
 
 
 
 
 
Triplicate 12-lead ECGi 
 
x 
xd 
 
 
xj 
 
 
 
 
 
Single 12-lead ECG 
 
 
 
 
 
xk 
 
x 
 
 
 
Clinical chemistry 
 
x 
xd 
x 
x 
x 
xl 
x 
x 
 
 
Thyroid panel 
 
x 
xd 
 
 
x 
 
x 
x 
 
 
Hematology 
 
x 
xd 
x 
x 
x 
xl 
x 
x 
 
 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
113 
Confidential 
24 July 2018 
9.0 
STUDY DISCONTINUATION 
9.1 
Sponsor Discontinuation Criteria 
This study may be discontinued at any time due to safety concerns, failure to meet expected 
enrollment goals, administrative reasons, or at the discretion of the Sponsor. Should the study be 
terminated prematurely, the Sponsor will provide written notification to all Investigators and 
regulatory authorities and will specify the reason(s) for early termination. The Investigator must 
inform the Institutional Review Board (IRB) promptly and provide the reason(s) for the 
termination. 
9.2 
Treatment Discontinuation for Individual Patients 
Patients may withdraw their consent to participate in the study at any time for any reason without 
prejudice to their future medical care by the physician or at the institution. If a patient withdraws 
consent, the date and stated reason for consent withdrawal should be documented. Patient data 
collected up to the date of consent withdrawal will be included in the analyses. Any blood or 
tissue samples collected up to the date of consent withdrawal will be analyzed. 
Wherever possible, the tests and evaluations listed for the Treatment Discontinuation Visit 
should be carried out and efforts should be made to continue follow-up. The Sponsor should be 
notified of all study withdrawals through the designated eCRFs in a timely manner. 
Patients meeting any of the following criteria should discontinue study drug treatment: 
• Withdrawal of consent (no further participation and thus no further protected health 
information may be collected) 
• Patient decision to discontinue study treatment (but agree to return for treatment 
discontinuation assessments (Section 8.3), safety follow-up (Section 8.4) and/or additional 
follow-up, if applicable (Section 8.5 and Section 8.6) 
• Unacceptable AEs or failure to tolerate study drug 
Note: For patients with melanoma, single-agent treatment with ARRY-382 is not 
recommended; if pembrolizumab is permanently discontinued for these patients, ARRY-382 
must also be discontinued. 
• Delay of > 21 days to start a subsequent treatment cycle unless judged by the Investigator to 
be in the best interest of the patient to continue treatment 
• Changes in the patient’s condition or development of an intercurrent illness which renders the 
patient unacceptable for further treatment in the judgment of the Investigator 
• Disease progression, as determined by the Investigator  


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
114 
Confidential 
24 July 2018 
• Patient becomes pregnant or begins breastfeeding 
• Significant protocol deviation that, in the opinion of the Investigator and/or Sponsor, renders 
the patient unsuitable for further study drug administration 
• Lost to follow-up 
• Discretion of Investigator 
• Termination of the study by the Sponsor (described in Section 9.1) 
9.3 
Replacement of Patients 
For Part A, patients will be replaced if they have received less than 67% dose intensity 
[(administered dose in mg/planned dose in mg) × 100] of ARRY-382 or if they did not receive 
pembrolizumab for any reason other than an AE or abnormal laboratory value that is not related 
to disease, disease progression, intercurrent illness or concomitant medications/therapies before 
completing Cycle 1.  
For the Phase 2 PD-1/PD-L1 Inhibitor Refractory cohort, patients who discontinue prior to study 
completion will not be replaced. 
For the Phase 2 prOVCA and PDA cohorts, additional patients will be enrolled to account for 
those who are found to be MSI-H/dMMR in order to evaluate the targeted patient population and 
to satisfy the Simon’s 2-stage design.  


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
115 
Confidential 
24 July 2018 
10.0 
SAFETY MONITORING: DEFINITIONS AND REPORTING 
10.1 
Adverse Event 
An AE is defined as any untoward medical occurrence, including the exacerbation of a 
pre-existing condition, in a patient administered an investigational (medicinal) product and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of investigational product, whether or not considered related 
to the investigational product. 
10.1.1 
Events Related to Progression of Disease 
Progression of malignancy (including fatal outcomes), if documented by use of appropriate 
method (for example, as per RECIST criteria for solid tumors) will be designated as progression 
of disease in the eCRF and should not be reported as an AE or SAE unless a causal relationship 
to study drug is suspected. 
10.1.2 
Clinical Laboratory Abnormalities 
An abnormal laboratory value that is not associated with an already reported AE is to be 
recorded as an AE only if an action on the study drug is made as a result of the abnormality, if 
intervention for management of the abnormality is required, or at the discretion of the 
Investigator. 
Laboratory abnormalities that meet the criteria for AEs should be followed until they have 
returned to normal or baseline, or per Investigator discretion. 
10.1.3 
Overdose 
An overdose of study drug (whether symptomatic or asymptomatic) will be reported as an AE. 
10.2 
Assessment of Severity 
The severity rating of an AE refers to its intensity. The severity of each AE will be determined 
by the Investigator using the National Cancer Institute (NCI) CTCAE, version 4.03 
(US Department of Health and Human Services 2010). For any term that is not specifically listed 
in the CTCAE scale, severity should be assigned a grade of 1 through 5 using the following 
CTCAE guidelines: 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
116 
Confidential 
24 July 2018 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care activities of 
daily living 
Grade 4: Life-threatening consequences; urgent intervention indicated 
Grade 5: Fatal 
10.3 
Assessment of Causality 
An assessment of causal relationship of study drug to each AE must be performed by the 
Investigator. Medical judgment should be used to determine the cause of the AE, considering all 
relevant factors such as (but not limited to) the underlying study indication, coexisting disease, 
concomitant medication, relevant history, pattern of the AE, temporal relationship to the study 
medication and de-challenge or re-challenge. 
Yes (possibly, probably or definitely related): there is a reasonable possibility that the study drug 
caused the event; 1 or more of the following criteria apply: 
• The event follows a reasonable temporal sequence from administration of study drug. 
• The event could not be reasonably attributed to the known characteristics of the patient’s 
clinical state, environmental or toxic factors or other modes of therapy administered to 
the patient. 
• The event follows a known pattern of response to study drug. 
• The event disappears or decreases on cessation or reduction in dose of the study drug. 
(It should be noted that in some situations an AE will not disappear or decrease in 
intensity upon discontinuation of study drug despite other clear indications of 
relatedness).  
• The event reappears or worsens when the study drug is re-administered. 
No (unlikely, probably not related or definitely not related): there is no reasonable possibility 
that the study drug caused the event; 1 or more of the following criteria apply: 
• The event does not follow a reasonable temporal sequence from administration of study 
drug. 


ARRY-382 (CSF-1R inhibitor) 
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• The event could be reasonably attributed to the known characteristics of the patient’s 
clinical state, concurrent illness, environment or toxic factors or other modes of therapy 
administered to the patient. 
• The event does not follow a known pattern of response to study drug. 
• The event does not disappear or decrease on cessation or reduction in dose of the study 
drug, and it does not reappear or worsen when the study drug is re-administered. 
10.4 
Assessment of Seriousness 
An AE is considered “serious” if it results in any of the following outcomes: 
• Results in death 
o Death is an outcome of an SAE and not an SAE in itself. When death is an 
outcome, the event(s) resulting in death should be reported (e.g., “pulmonary 
embolism” with a fatal outcome) and assigned severity Grade 5. 
o Death should only be reported as an SAE term when no additional information is 
known about a fatal event. 
• Is immediately life-threatening (its occurrence places the patient at immediate risk of 
death. It does not include an event that, had it occurred in a more severe form, might have 
caused death) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
Note: Hospitalization includes any hospital admission, even if for less than 
24 hours. The following do not meet hospitalization serious criteria:  
 A visit to the emergency room, or outpatient observation that does not 
result in admission 
 Elective surgery, planned prior to signing consent 
 Routine health assessment requiring admission  
• Results in a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• Is a congenital anomaly/birth defect 
• Based upon appropriate medical judgment, represents an important medical event that 
may jeopardize the patient or may require intervention to prevent one of the outcomes 
described above 


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Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
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10.5 
Reporting of Serious and Nonserious Adverse Events 
All AEs, serious and nonserious (including the exacerbation of a pre-existing condition) and 
regardless of causality to study drug will be fully recorded on the appropriate eCRF. For each 
AE, the Investigator must provide its duration (start and end dates or ongoing), severity 
(intensity), assessment of causality, whether specific action or therapy was required, and whether 
action was taken with regard to study drug treatment. 
Any AE that occurs from the signing of the informed consent until the first dose of study drug is 
to be recorded on the AE eCRF only if the event was related to a study procedure. All other 
AEs/findings prior to the first dose of study drug should be recorded on the medical history 
eCRF. All AEs occurring from the first dose of study drug until 30 days after the last dose of 
study drug must be recorded on the AE eCRF, regardless of causal relationship to investigational 
product. SAEs occurring greater than 30 days after the last dose of study drug should be reported 
only if considered related to investigational product. 
In addition to recording SAEs on the AE eCRF, all SAEs must be reported to the Sponsor within 
24 hours of the Investigator’s knowledge by faxing the completed SAE form to the Sponsor at 
the number provided on the SAE form or fax cover sheet. If new information becomes available 
for a previously reported SAE, a follow-up SAE report should be sent within 24 hours. 
Investigators must follow patients with AEs/SAEs until the event has resolved, the condition has 
stabilized, withdrawal of consent, the patient is lost to follow-up or death OR until 30 days after 
the last dose of study drug, whichever occurs first. Ongoing treatment-related SAEs may be 
followed beyond this time period if clinically indicated. 
10.6 
Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) 
Suspected unexpected serious adverse reactions (SUSARs) will be collected and reported by the 
Sponsor and/or designee to the competent authorities and relevant ethics committees in 
accordance with Directive 2001/20/EC or as per national regulatory requirements in participating 
countries. 
10.7 
Pregnancy or Drug Exposure During Pregnancy 
If a patient becomes pregnant during the study, administration of study drug is to be discontinued 
immediately. 
Pregnancies (both those of female patients and female partners of male patients) must be 
reported to the Sponsor or designee within 24 hours of the Investigator’s knowledge using the 
pregnancy reporting form. All pregnancies will be followed through to outcome and the outcome 
must be reported to the Sponsor or designee using the pregnancy outcome form.  


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
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Pregnancies themselves are not considered AEs or SAEs. However, any AEs or SAEs occurring 
during pregnancy are to be reported following AE and SAE reporting guidelines. 
10.8 
Review of Safety Data 
The Medical Monitor will be responsible for the ongoing review and evaluation of safety data, 
including AEs, laboratory data, and any other safety evaluations, throughout the duration of the 
study.  


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Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
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11.0 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
11.1 
General Considerations 
A detailed statistical analysis plan (SAP) will be prepared by the Sponsor or designee. This plan 
may modify the statistical methods outlined in the protocol; however, any major modifications of 
the primary endpoint definition or analysis (in any part of the study) will also be described in a 
protocol amendment. 
11.1.1 
Sample Size 
Overall, approximately 90 patients are planned for enrollment. 
For Part A, the sample size of approximately 18 evaluable patients (i.e., 6 to 9 patients in each 
dose cohort) is standard for purposes of determining the MTD and RP2D. Patients will be 
considered evaluable if they receive at least 67% of protocol-specified doses of ARRY-382 
during Cycle 1 or have an AE or other event as described in Section 9.3. The binomial 
probabilities of observing a DLT in a cohort of 6 and 9 patients, assuming a true rate of 33%, are 
provided in Table 12 and Table 13, respectively. 
Table 12: 
Binomial Probabilities of Dose-Limiting Toxicity in a Cohort of 6 Patients 
 
Binomial Probability 
K 
Exactly k DLTs 
≤ k DLTs 
>k DLTs 
0 
0.0878 
0.0878 
0.9122 
1 
0.2634 
0.3512 
0.6488 
2 
0.3292 
0.6804 
0.3196 
3 
0.2194 
0.8998 
0.1002 
4 
0.0823 
0.9821 
0.0179 
5 
0.0165 
0.9986 
0.0014 
6 
0.0014 
1.0000 
0.0000 
DLT = dose-limiting toxicity; k = number of dose-limiting toxicities 


ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
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Table 13: 
Binomial Probabilities of Dose-Limiting Toxicity in a Cohort of 9 Patients 
 
Binomial Probability 
K 
Exactly k DLTs 
≤ k DLTs 
>k DLTs 
0 
0.0260 
0.0260 
0.9740 
1 
0.1171 
0.1431 
0.8569 
2 
0.2341 
0.3772 
0.6228 
3 
0.2731 
0.6503 
0.3497 
4 
0.2048 
0.8552 
0.1448 
5 
0.1024 
0.9576 
0.0424 
6 
0.0341 
0.9917 
0.0083 
7 
0.0073 
0.9990 
0.0010 
8 
0.0009 
0.9999 
0.0001 
9 
0.0001 
1.0000 
0.0000 
DLT=dose-limiting toxicity; k=number of dose-limiting toxicities 
For the Phase 2 PD-1/PD-L1 Inhibitor Refractory cohort, the sample size of approximately 
20 patients will be evaluated for initial evidence of activity in this PD-1/PD-L1 refractory 
population. 
For the Phase 2 prOVCA cohort, a Simon’s 2-stage optimal design (Simon 1989) will be used in 
the MSS/MMR-proficient prOVCA population. The null hypothesis of the true response rate is 
15%, versus alternative of 35%. Accrual of patients in Stage 1 will continue until 9 evaluable 
MSS/MMR-proficient patients have been enrolled, with evaluable defined as having received at 
least one dose of study drug. The analysis for Stage 1 will not occur until all evaluable patients in 
Stage 1 have had the opportunity to have at least 2 post-baseline tumor assessments (or have 
discontinued tumor assessments beforehand). If there are less than 2 responders in these 9 
patients, enrollment into this cohort of the study will be stopped. Otherwise, 14 additional 
patients will be accrued during Stage 2, for a total of 23 patients enrolled in this cohort. The null 
hypothesis will be rejected if 6 or more responses are observed in 23 patients. With this sample 
size, the actual Type I error is 9.9%, and the power is 80%. If the null hypothesis is true, the 
expected sample size is 15 patients, and the probability of stopping enrollment into this cohort of 
the study early is 60%. Patients who are MSI-H/mismatch repair-deficient (dMMR) will not be 
included in the Simon’s 2-stage analyses and the study will ensure that the sample size 
requirements are met by enrolling the required number of MSS/MMR-proficient prOVCA 
patients. 


A R R Y -3 8 2  (C S F -1 R i n hi bit o r) 
Arra y Bi o P har ma I nc.  
Cli nical St u d y A R R A Y -3 8 2 -2 0 1  
 
Versi o n 4  
1 2 2  
C o nfi de ntial  
2 4 J ul y 2 0 1 8  
F or t he P hase 2 P D A c o h ort , a Si m o n’s 2- sta ge o pti mal desi g n ( Si m o n 1 9 8 9) will be use d  i n t he 
M S S/ M M R - pr oficie nt P D A p o p ulati o n. T he n ull h y p ot hesis of t he tr u e res p o nse rate is 4 %, 
vers us alter n ati ve of 1 5 %.  Accr ual of p atie nts i n Sta ge 1 will c o nti n ue u ntil 1 5 e val ua ble 
M S S/ M M R - pr oficie nt patie nts ha ve bee n e nr olle d, wit h e val ua ble defi ne d as ha vi n g recei ve d at 
least o ne d ose of st u d y dr u g. T he a nal ysis f or Sta ge 1 will n ot occ ur u ntil all e val ua ble patie nts i n 
Sta ge 1 h a ve ha d t h e o p p ort u nit y t o ha ve at least 2 p ost- baseli ne t u m or assess me nts  ( or ha ve 
disc o nti n ue d t u m or assess me nts bef ore h a n d). If t here are n o res p o n ders i n t hese 1 5 patie nts, 
e nr oll me nt i nt o t his c o h ort of t he st u d y will be st o p pe d. Ot her wise, 1 4 a d diti o nal M S S/ M M R -
pr oficie nt patie nts will be accr ue d d uri n g Sta ge 2, f or a t otal of 2 9 patie nts e nr olle d i n t his 
c o h ort. T he n ull h y p ot hesis will be rejecte d if 3 or m ore res p o nses are o bs er ve d i n 
2 9 M S S/ M M R - pr oficie nt patie nts. Wit h t his sa m ple size, t he act ual T y pe I err or is 9. 9 %, a n d t h e 
p o wer is 8 0 %. If t he n ull h y p ot hesis is tr ue, t he e x pecte d sa m ple size is 2 1 patie nts, a n d t he 
pr o ba bilit y of st o p pi n g e nr oll me nt i nt o t his c o h ort of t he st u d y earl y is 5 4 %. P D A p atie nts w h o 
are M SI-H/ d M M R  will n ot be i ncl u de d i n t he Si m o n’s 2-sta ge a n al yses a n d t he st u d y will e ns ure 
t hat t he sa m ple size re q uire me nts ar e met b y e nr olli n g t he re q uire d n u m ber of M S S/ M M R -
pr oficie nt P D A p atie nts.  
1 1. 1. 2  
Effic ac y  A n al ysis 
1 1. 1. 2. 1  
Effic ac y A n al yses Usi n g Res p o nse Criteri a i n S oli d T u m ors  
O bjecti ve res p o ns e usi n g R E CI S T will be defi ne d as C R + P R, as deter mi ne d b y t h e 
I n v esti gat or. O bjecti ve res p o nse rate is defi ne d as t he pr o p orti o n of patie nts w h o ac hie v e a n 
o bjecti ve res p o nse. T he o bjecti ve res p o nse rate al o n g wit h e x act 9 5 % C Is (Cl o p per a n d Pears o n 
1 9 3 4 ) will be re p orte d.  
D urati o n of res p o ns e will be calc ul ate d f or p atie nts w h o ac hie ve a n o bjecti ve res p o nse (i.e., C R 
or P R , as deter mi ne d b y t he I n vesti gat or) a n d is defi ne d as t he ti me fr o m t h e first d oc u me nte d 
res p o nse t o t he date of d oc u me nte d pr o gressi o n or deat h after ac hie vi n g a res p o nse. If a patie nt 
has n ot ha d a P F S e v e nt at t he ti me of t he a nal ysis c ut off or at t he start of a n y n e w a nti ne o pl astic 
t hera p y, d ur ati o n of res p o nse is ce ns ore d at t he date of last a de q u ate t u m or assess me nt. T he 
s ur vi val distri b uti o n f u ncti o n f or d urati o n of res p o nse will be esti mate d usi n g t he K a pla n-M eier 
met h o d. 
Pr o gr essi o n- fr ee s ur vi val is defi ne d as t he ti me fr o m t he start of treat me nt t o t he ti me of first 
d oc u me nte d pr o gr essi o n or deat h, w hic h e ver o cc urs first. If a p atie nt has n ot ha d a P F S e ve nt at 
t he ti me of t he a nal ysis c ut- off or at t he start of a n y ne w a nti-ne o plastic t h era p y, P F S is ce ns ore d 
at t he date of last a de q uat e t u m or assess me nt. T he s ur vi val distri b uti o n f u ncti o n f or P F S will be 
esti mate d usi n g t he K a pl a n - Meier m et h o d.  
O verall s ur vi val is defi n e d as t he ti me fr o m t he start of treat me nt  t o t he dat e of deat h d ue t o a n y 
ca use. If a deat h has n ot bee n o bser v e d b y t he dat e of t he a n al ysis c ut off, O S will be ce ns ore d at 


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ARRY-382 (CSF-1R inhibitor) 
Array BioPharma Inc. 
Clinical Study ARRAY-382-201 
 
Version 4 
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24 July 2018 
12.0 
DATA RECORDING, RETENTION AND MONITORING 
12.1 
Case Report Forms 
Data will be collected using an electronic data capture system (EDC) at the clinical site. The 
Investigator or designee will record data specified in the protocol using eCRFs. Changes or 
corrections to eCRFs will be made by the Investigator or an authorized member of the study staff 
according to the policies and procedures at the site. 
It is the Investigator’s responsibility to ensure eCRFs are complete and accurate. Following 
review and approval, the Investigator will electronically sign and date the pages. This signature 
certifies that the Investigator has thoroughly reviewed and confirmed all data on the eCRF. 
A portable document format (PDF) file of the eCRFs will be provided to the site after all data 
have been monitored and reconciled. An electronic copy will be archived at the site. 
12.2 
Data Monitoring 
This study will be closely monitored by representatives of the Sponsor throughout its duration. 
Monitoring will include personal visits with the Investigator and study staff as well as 
appropriate communications by telephone, fax, mail, email or use of the EDC system, if 
applicable. It is the monitor’s responsibility to inspect eCRFs at regular intervals throughout the 
study to verify the completeness, accuracy and consistency of the data and to confirm adherence 
to the study protocol and to Good Clinical Practice (GCP) guidelines. The Investigator agrees to 
cooperate with the monitor to ensure that any problems detected during the course of this study 
are resolved promptly. The Investigator and site will permit study-related monitoring, audits, EC 
review and regulatory inspection, including direct access to source documents. 
It is understood that study monitors and any other personnel authorized by the Sponsor may 
contact and visit the Investigator and will be permitted to inspect all study records (including 
eCRFs and other pertinent data) on request, provided that patient confidentiality is maintained 
and that the inspection is conducted in accordance with local regulations. 
Every effort will be made to maintain the anonymity and confidentiality of patients during this 
study. However, because of the experimental nature of this treatment, the Investigator agrees to 
allow representatives of the Sponsor as well as authorized representatives of regulatory 
authorities to inspect the facilities used in the conduct of this study and to inspect, for purposes 
of verification, the hospital or clinic records of all patients enrolled in the study. 


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12.3 
Quality Control and Quality Assurance 
Quality control procedures will be conducted according to the Sponsor’s internal procedures. 
The study site may be audited by a quality assurance representative of the Sponsor. All necessary 
data and documents will be made available for inspection. 


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13.0 
REGULATORY, ETHICAL AND LEGAL OBLIGATIONS 
13.1 
Good Clinical Practice 
The study will be performed in accordance with the protocol, guidelines for GCP established by 
the International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) and applicable local regulatory requirements and laws.  
13.2 
Ethics Committee Approval 
The Investigator must inform and obtain approval from the EC for the conduct of the study at 
named sites, the protocol, informed consent documents and any other written information that 
will be provided to the patients and any advertisements that will be used. Written approval must 
be obtained prior to recruitment of patients into the study and shipment of study drug. 
Proposed amendments to the protocol and aforementioned documents must be submitted to the 
Sponsor for review and approval, then to the EC. Amendments may be implemented only after a 
copy of the approval letter from the EC has been transmitted to the Sponsor. Amendments that 
are intended to eliminate an apparent immediate hazard to patients may be implemented prior to 
receiving Sponsor or EC approval. However, in this case, approval must be obtained as soon as 
possible after implementation. 
Per GCP guidelines, the Investigator will be responsible for ensuring that an annual update is 
provided to the EC to facilitate continuing review of the study and that the EC is informed about 
the end of the study. Copies of the update, subsequent approvals and final letter must be sent to 
the Sponsor. 
13.3 
Regulatory Authority Approval 
The study will be performed in accordance with the requirements of each country’s regulatory 
authorities, e.g., US FDA and will also meet all of the requirements of ICH GCP guidance. 
Amendments to the protocol will be submitted to the relevant authorities prior to implementation 
in accordance with applicable regulations. 
13.4 
Other Required Approvals 
In addition to EC and regulatory authority approval, all other required approvals (e.g., approval 
from the local research and development board or scientific committee) will be obtained prior to 
recruitment of patients into the study and shipment of study drug. 
13.5 
Informed Consent 
Informed consent is a process that is initiated prior to the patient’s agreeing to participate in the 
study and continues throughout the patient’s study participation. It is the Investigator’s 


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Version 4 
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responsibility (or designee) to obtain written informed consent from each patient after adequate 
explanation of the aims, methods, anticipated benefits and potential hazards of the study and 
before any study procedures are initiated. Each patient should be given a copy of the informed 
consent document and associated materials. The original copy of the signed and dated informed 
consent document must be retained at the site and is subject to inspection by representatives of 
the Sponsor or regulatory authorities. If any amendments occur throughout the course of the 
study that affect the informed consent form (i.e., when new study procedures or assessments 
have been added), all active patients should be reconsented using the same process for the initial 
consent. 
13.6 
Patient Confidentiality 
The Investigator must ensure that the patient’s privacy is maintained. On the eCRF or other 
documents submitted to the Sponsor, patients will be identified by a patient number only. 
Documents that are not submitted to the Sponsor (e.g., signed informed consent documents) 
should be kept in a confidential file by the Investigator. 
The Investigator shall permit authorized representatives of the Sponsor, regulatory authorities 
and ethics committees to review the portion of the patient’s medical record that is directly related 
to the study. As part of the required content of informed consent documents, the patient must be 
informed that his/her records will be reviewed in this manner. 
13.7 
Disclosure of Information 
Information concerning the study, patent applications, processes, scientific data or other pertinent 
information is confidential and remains the property of the Sponsor. The Investigator may use 
this information for the purposes of the study only. 
It is understood by the Investigator that the Sponsor will use information obtained in this clinical 
study in connection with the clinical development program, and therefore may disclose it as 
required to other clinical Investigators and to regulatory authorities. In order to allow the use of 
the information derived from this clinical study, the Principal Investigator understands that 
he/she has an obligation to provide complete test results and all data obtained during this study to 
the Sponsor. 
Verbal or written discussion of results prior to study completion and full reporting should only 
be undertaken with written consent from the Sponsor. 
13.8 
Publication of Study Data 
The conditions regulating dissemination of the information derived from this study are described 
in the Clinical Trial Agreement. 


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14.0 
ADHERENCE TO THE PROTOCOL 
Investigators must apply due diligence to avoid protocol deviations, and the Sponsor (and 
designee[s]) will not pre-authorize deviations. If the Investigator believes a change to the 
protocol would improve the conduct of the study, this must be considered for implementation in 
a protocol amendment. Protocol deviations will be recorded. 
14.1 
Amendments to the Protocol 
Only the Sponsor may modify the protocol. Amendments to the protocol will be made only after 
consultation and agreement between the Sponsor and the Investigator. The only exception is 
when the Investigator considers that a patient’s safety is compromised without immediate action. 
In these circumstances, immediate approval of the chairman of the EC must be sought, and the 
Investigator should inform the Sponsor and the full EC within 5 working days after the 
emergency occurred. All amendments that have an impact on patient risk or the study objectives 
or require revision of the informed consent document must receive approval from the EC prior to 
implementation. 


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REFERENCES 
American Cancer Society. Key Statistics for Ovarian Cancer, 05 January 2018. Available from: 
<https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html> 
(Accessed 18 February 2018). 
Brahmer JR, Tykodi SS, Chow LQ et al. Safety and activity of anti-PD-L1 antibody in patients 
with advanced cancer. N Eng J Med 2012;366(26):2455-65. 
Champiat S, Lambotte O, Barreau E et al. Management of immune checkpoint blockade 
dysimmune toxicities: a collaborative position paper. Ann Oncol 2016;27:559-74. 
Chen JJW, Lin Y-C, Yao P-L et al. Tumor-Associated Macrophages: The Double-Edged Sword 
in Cancer Progression. J Clin Oncol 2005;23(5):953-64. 
ClinicalTrials.gov NCT02323191. A study of emactuzumab and atezolizumab administered in 
combination in participants with advanced solid tumors. 
<https://www.clinicaltrials.gov/ct2/show/NCT02323191?term=NCT02323191&rank=1> 
(Accessed 28 February 2018). 
ClinicalTrials.gov NCT02452424. A combination clinical study of PLX3397 and 
pembrolizumab to treat advanced melanoma and other solid tumors. 
<https://www.clinicaltrials.gov/ct2/show/NCT02452424?term=NCT02452424&rank=1> 
(Accessed 28 February 2018). 
ClinicalTrials.gov NCT02526017. Study of FPA008 in combination with nivolumab in patients 
with selected advanced cancers (FPA008-003). 
<https://www.clinicaltrials.gov/ct2/show/NCT02526017?term=NCT02526017&rank=1> 
(Accessed 28 February 2018). 
ClinicalTrials.gov NCT02674061. Efficacy and safety study of pembrolizumab (MK-3475) in 
women with advanced recurrent ovarian cancer (MK-3475-100/KEYNOTE-100). 
<https://clinicaltrials.gov/ct2/show/NCT02674061?term=NCT02674061&rank=1> (Accessed 18 
February 2018). 
Clinical Trials Facilitation Group (CTFG) Recommendations related to contraception and 
pregnancy testing in clinical trials. Final Version 2014-09-15; 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf 
(Accessed 12 March 2018). 
Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial. Biometrika 1934;26(4):404-13. 


ARRY-382 (CSF-1R inhibitor) 
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DeNardo DG, Brennan DJ, Rexhepaj E et al. Leukocyte complexity predicts breast cancer 
survival and functionally regulates response to chemotherapy. Cancer Discov 2011(1);1:54–67. 
Devaud C, John LB, Westwood JA et al. Immune modulation of the tumor microenvironment for 
enhancing cancer immunotherapy. OncoImmunology 2013;2(8):e25961-1-9. 
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al. Cancer incidence and mortality patterns in 
Europe: estimates for 40 Countries in 2012. Eur J Cancer 2013;49:1374-1403. 
Garon EB, Rizvi NA, Hui R et al. Pembrolizumab for the treatment of non-small-cell lung 
cancer. N Engl J Med 2015;372:2018-28. 
Hamanishi J, Mandai M, Ikeda T et al. Safety and antitumor activity of anti-PD-1 antibody, 
nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 2015;33(34):4015-
22. 
Hanna N, Shepherd FA, Fossella FV et al. Randomized Phase III trial of pemetrexed versus 
docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J 
Clin Oncol 2004;22(9):1589-97. 
Harb WA, Johnson ML, Goldman JW et al. A phase 1b/2 dose-escalation study of ARRY-382, 
an oral inhibitor of colony-stimulating factor-1 receptor (CSF1R), in combination with 
pembrolizumab for the treatment of patients with advanced solid tumors. Presented at the 32nd 
Annual Meeting of the Society for Immunotherapy of Cancer. November 8–12, 2017. National 
Harbor, MD, USA. Abstract P271. 
Herbst RS, Soria JC, Kowanetz M et al. Predictive correlates of response to the anti-PD-L1 
antibody MPDL3280A in cancer patients. Nature 2014;515:563-7. 
Herbst RS, Baas P, Kim DW et al. Pembrolizumab versus docetaxel for previously treated, PD-
L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled 
trial. Lancet 2016;387(10027):1540-50. 
Herzog TJ and Monk BJ. Bringing new medicines to women with epithelial ovarian cancer: what 
is the unmet medical need? Gynecol Oncol Res Pract. 2017;4:13. 
Huang S, Van Arsdall M, Tedjarati S et al. Contributions of stromal metalloproteinase-9 to 
angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst 2002;94:1134–
42. 
Hugo W, Zaretsky JM, Sun L et al. Genomic and transcriptomic features of response at anti-PD-
1 therapy in metastatic melanoma. Cell 2016;165:35-44. 


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Hui R, Garon EB, Goldman JW et al. Pembrolizumab as first-line therapy for patients with PD-
L1-positive advanced non-small cell lung cancer: a phase 1 trial. Ann Oncol 2017;28:874-81. 
Hume DA and MacDonald KPA. Therapeutic applications of macrophage colony-stimulating 
factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood 
2012;119(8):1810-20. 
Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint 
inhibitors. Br J Cancer 2018;118(1):9-16. 
Johansson H, Andersson R, Bauden M et al. Immune checkpoint therapy for pancreatic cancer. 
World J Gastroenterol 2016;22(43):9457-76. 
Kaminska J, Kowalska M, Koftowicz B et al. Pretreatment Serum Levels of Cytokines and 
Cytokine Receptors in Patients with Non-Small Cell Lung Cancer, and Correlations with 
Clinicopathological Features and Prognosis. Oncology 2006;70:115-25. 
Keytruda® (pembrolizumab) summary of product characteristics. EPAR-Product Information. 
Last updated 16 January 2018. Available from: 
<http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003820/hum
an_med_001886.jsp&mid=WC0b01ac058001d124> 
(Accessed 18 February 2018).  
Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). 
Ann Oncol 2016; 27(8):1492-504. 
Kluger HM, Dolled-Filhart M, Rodov S et al. Macrophage colony-stimulating factor-1 receptor 
expression is associated with poor outcome in breast cancer by large cohort tissue microarray 
analysis. Clin Cancer Res 2004;10:173-7. 
Larkin J, Chiarion-Seleni V, Gonzalez R et al. Combined nivolumab and ipilimumab or 
monotherapy in untreated melanoma. N Engl J Med 2015;373:23-34. 
Leek RD, Lewis CE, Whitehouse R et al. Association of macrophage infiltration with 
angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 1996;56:4625-9. 
Lissbrant IF, Stattin P, Wikstrom P et al. Tumor associated macrophages in human prostate 
cancer: relation to clinicopathological variables and survival. Int J Oncol 2000;17:445-51. 
Mantovani A, Sozzani S, Locati M et al. Macrophage polarization: tumor-associated 
macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 
2002;23(11):549-55. 


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Naidoo J, Page DB, Li BT et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint 
antibodies. Ann Oncol 2015; 26:2375-91. 
Nakata B, Wang YQ, Yashiro M et al. Prognostic value of microsatellite instability in resectable 
pancreatic cancer. Clin Cancer Res 2002;8(8):2536-40. 
Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin 
Oncol 2015;33(17):1974-82. 
Pujade-Lauraine E, Hilpert F, Weber B et al. Bevacizumab combined with chemotherapy for 
platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III 
trial. J Clin Oncol 2014;32:1302-08. 
Qian B-Z and Pollard JW. Macrophage density enhances tumor progression and metastasis. Cell 
2010;141:39-51. 
Radi ZA, Koza-Taylor PH, Bell RR et al. Increased serum enzyme levels associated with 
Kupffer cell reduction with no signs of hepatic or skeletal muscle injury. Am J Pathol 
2011;197:240-7. 
Reck M, Rodríguez-Abreu D, Robinson AG et al. Pembrolizumab versus chemotherapy for PD-
L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823-33. 
Restifo NP, Smyth MJ, Snyder A. Acquired resistance to immunotherapy and future challenges. 
Nat Rev Cancer. 2016;16(2):121-6. 
Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular 
carcinoma. Nat Clin Pract Oncol 2007;4(7):424-32. 
Shah CA, Allison KH, Garcia RL et al. Intratumoral T cells, tumor-associated macrophages, and 
regulatory T cells: Association with p53 mutations, circulating tumor DNA and survival in 
women with ovarian cancer. Gynecol Oncol 2008;109:215-9. 
Simon R. Optimal two-stage designs for Phase II Clinical Trials. Control Clin Trials 
1989;10(1):1-10. 
Stanley ER, Berg KL, Einstein DB et al. Biology and action of colony--stimulating factor-1. Mol 
Reprod Dev 1997;46:4-10. 
Takanami IK, Takeuchi K, Kodaira S. Tumor-associated macrophage infiltration in pulmonary 
adenocarcinoma: association with angiogenesis and poor prognosis. Oncology 1999;57:138-42. 
Topalian SL, Hodi FS, Brahmer JR et al. Safety, activity, and immune correlates of anti PD 1 
antibody in cancer. N Engl J Med 2012;366 (26):2443-54. 


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Tsutsui S, Yasuda K, Suzuki K et al. Macrophage infiltration and its prognostic implications in 
breast cancer: the relationship with VEGF expression and microvessel density. Oncol Rep 
2005;14:425-31. 
US Cancer Statistics Working Group. United States Cancer Statistics: 1999-2012 Incidence and 
Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers 
for Disease Control and Prevention, and National Cancer Institute; 2015. 
US Department of Health and Human Services, National Institutes of Health. Common 
Terminology Criteria for Adverse Events (CTCAE) Version 4.0. 28 May 2009 (v4.03: 14 June 
2010). Available from:  
<https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf> (Accessed 18 February 2018). 
Varga A, Piha-Paul SA, Ott PA et al. Pembrolizumab in patients (pts) with PD-L1–positive (PD-
L1+) advanced ovarian cancer: Updated analysis of KEYNOTE-028. J Clin Oncol 2017 35(15) 
suppl. 5513. 
Wainburg Z, Piha-Paul S, Luke J et al. First-in-human phase 1 dose escalation and expansion of 
a novel combination, anti–CSF‐1 receptor (cabiralizumab) plus anti–PD‐1 (nivolumab), in 
patients with advanced solid tumors. Presentation at The Society for Immunotherapy of Cancer 
Annual Meeting, 2017; Baltimore, MD. Abstract O42. 
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. 
Zhu Y, Knolfhoff BL, Meyer MA et al. CSF1/CSF1R blockade reprograms tumor-infiltrating 
macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer 
models. Cancer Res 2014;74(18):5057-69. 


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Appendix 1 Eastern Cooperative Oncology Group Performance Status 
 
ECOG PS 
Definition 
0 
Asymptomatic 
1 
Symptomatic, but fully ambulatory 
2 
Symptomatic, in bed less than 50% of the day 
3 
Symptomatic, in bed more than 50% of the day, but not bedridden 
4 
Bedridden 
5 
Dead 
ECOG PS = Eastern Cooperative Oncology Group performance status 
 


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Appendix 2 Drugs with Risk of TDP/Potential to Prolong QT Interval and CYP3A 
Inhibitors/Inducers 
 
STRONG CYP3A INHIBITORS AND INDUCERS 
Category 
Drugs 
Strong CYP3A inhibitors 
boceprevir 
clarithromycin 
cobicistat 
conivaptan 
elvitegravir 
indinavir 
itraconazole 
ketoconazole,  
lopinavir 
mibefradil 
nefazodone 
nelfinavir, 
posaconazole 
ritonavir 
saquinavir 
telaprevir, 
telithromycin 
tipranavir 
troleandomycin 
voriconazole 
Strong CYP3A inducers 
avasimibe 
carbamazepine 
mitotane 
phenobarbital 
phenytoin 
rifabutin 
rifampin (rifampicin) 
St. John's wort (hypericum 
perforatum) 
Note:  
Compiled from the Indiana University School of Medicine “Clinically Relevant” Table, FDA Guidance for 
Industry, Drug Interaction Studies and the University of Washington Drug Interaction Database 
 
 
DRUGS WITH RISK OF TORSADES DE POINTES/POTENTIAL TO PROLONG QT 
INTERVAL 
amiodarone 
arsenic trioxide 
[astemizole] 
azithromycin 
bepridil 
chlorpromazine 
chloroquine 
[cisapride] 
citalopram 
clarithromycin 
disopyramide 
dofetilide 
[domperidone] 
 droperidol 
erythromycin 
flecainide 
halofantrine 
[haloperidol] 
ibutilide 
[levomethadyl] 
mesoridazine 
methadone 
moxifloxacin 
pentamidine 
pimozide 
Notes: Substantial evidence supports the conclusion that these drugs prolong QT intervals and 
have a risk of torsade de pointes when used as directed in labeling.  
 
 
Drugs in brackets are not marketed in US. 


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Appendix 3 Child Pugh Classification 
 
Points 
Measure 
1 
2 
3 
Bilirubin (mg/dL) 
<2.0 
2.0-3.0 
>3.0 
Albumin (g/dL) 
>3.5 
2.8-3.5 
<2.8 
PT (INR) 
<1.7 
1.7-2.3 
>2.3 
Ascites 
Absent 
Mild to moderate 
Severe/refractory 
Encephalopathy (grade)* 
Absent 
Mild (1-2) 
Severe (3-4) 
*Grade 0: normal consciousness, personality, neurological examination, electroencephalogram 
  Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cps waves 
  Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves 
  Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves 
  Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity 
 
Class A=5-6 points; Class B=7-9 points; Class C=10-15 points; Abbreviations: PT, prothrombin time; INR, International 
Normalized Ratio. 
Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol 
2007;424-32. 
US Department of Health and Human Services, Food and Drug Administration. Guidance for Industry: Pharmacokinetics in 
Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling. May 2003. 
Available from: <https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072123.pdf> 
(Accessed on 06 November 2017). 


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Appendix 4 Concomitant Medications to Be Used with Caution 
CONCOMITANT MEDICATIONS TO BE USED WITH CAUTION 
Category 
Drugs 
P-gp inhibitors 
amiodarone 
azithromycin 
captopril 
carvedilol 
clarithromycin 
conivaptan 
cyclosporine 
diltiazem 
dronedarone 
elacridar (GF120918) 
erythromycin 
felodipine 
fexofenadine 
fluvoxamine 
indinavir 
indinavir/ritonavir 
itraconazole 
ketoconazole 
lopinavir/ritonavir 
mibefradil 
nelfinavir 
paroxetine 
quercetin 
quinidine 
ranolazine 
telaprevir 
saquinavir/ritonavir 
ticagrelo 
tipranavir/ritonavir 
valspodar (PSC 833) 
verapamil 
P-gp inducers 
avasimibe 
carbamazepine 
phenytoin 
rifampin 
St John’s wort 
tipranavir/ritonavir 
Moderate CYP3A 
inhibitors 
amprenavir 
aprepitant 
atazanavir 
atazanavir/ritonavir 
casopitant 
cimetidine 
ciprofloxacin 
crizotinib 
cyclosporine 
duranavir 
darunavir/ritonavir 
diltiazem 
dronedarone 
erythromycin 
fluconazole 
fosamprenavir 
grapefruit juice 
imatinib 
lomitapide 
netupitant 
nilotinib 
schisandra 
sphenanthera 
tofisopam 
verapamil 


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CONCOMITANT MEDICATIONS TO BE USED WITH CAUTION (continued) 
Weak CYP3A 
inhibitors 
almorexant 
alprazolam 
amiodarone 
amlodipine 
atorvastatin 
azithromycin 
berberine 
bicalutamide 
blueberry juice 
cilostazol 
cimetidine 
clotrimazole 
clozoxazone 
cranberry juice 
cyclosporine 
delavirdine 
evrolimus 
fluoxetine 
fluvoxamine 
fosaprepritantranolaxine 
ginkgo 
goldenseal 
isoniazid 
ivacaftorlacipidine linagliptin 
nilotinib 
oral contraceptives 
pazopanib 
peppermint oil 
propiverine 
ranitidine 
ranolazine 
resveratrol 
roxithromycin 
Seville orange 
simeprevir 
tabimorelin 
tacrolimus 
ticagrelor 
tolvaptan 
sitaxentan 
teriflunomide 
tipranavir/ritonavir 
zileuton 
Note: 
Compiled from the Indiana University School of Medicine “Clinically Relevant” Table, FDA Guidance for 
Industry, Drug Interaction Studies and the University of Washington Drug Interaction Database 
 
 


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Appendix 5 Response Criteria in Solid Tumors, Version 1.1 
1.0 Response and Evaluation Endpoints 
Response and progression will be evaluated in this study using the revised international criteria 
(1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumors) committee. 
1.1.1 Measurable Disease 
Measurable tumor lesions are defined as those that can be accurately measured in at least 
1 dimension (longest diameter to be recorded) as ≥ 20 mm with chest x-ray and as ≥ 10 mm with 
computerized tomography (CT) scan or clinical examination. Bone lesions are considered 
measurable only if assessed by CT scan and have an identifiable soft tissue component that 
meets these requirements (soft tissue component > 10 mm by CT scan). Malignant lymph nodes 
must be ≥ 15 mm in the short axis to be considered measurable; only the short axis will be 
measured and followed. All tumor measurements must be recorded in millimeters (or decimal 
fractions of centimeters). Previously irradiated lesions are not considered measurable unless 
progression has been documented in the lesion. 
1.1.2 Nonmeasurable Disease 
All other lesions (or sites of disease), including small lesions are considered non-measurable 
disease. Bone lesions without a measurable soft tissue component, leptomeningeal disease, 
ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, 
lymphangitic involvement of lung or skin and abdominal masses followed by clinical 
examination are all non-measurable. Lesions in previously irradiated areas are non-measurable, 
unless progression has been demonstrated. 
1.1.3 Target Lesions 
When more than 1 measurable tumor lesion is present at baseline all lesions up to a maximum of 
5 lesions total (and a maximum of 2 lesions per organ) representative of all involved organs 
should be identified as target lesions and will be 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 organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. Note that pathological nodes must meet the criterion of a 
short axis of ≥ 15 mm by CT scan and only the short axis of these nodes will contribute to the 
baseline sum. 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 
nonpathological and should not be recorded or followed. At baseline, the sum of the target 
lesions (longest diameter of tumor lesions plus short axis of lymph nodes: overall maximum of 
5) is to be recorded. 


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After baseline, a value should be provided on the eCRF for all identified target lesions for each 
assessment, even if very small. If extremely small and faint lesions cannot be accurately 
measured but are deemed to be present, a default value of 5 mm may be used. If lesions are too 
small to measure and indeed are believed to be absent, a default value of 0 mm may be used. 
1.1.4 Nontarget Lesions 
All nonmeasurable lesions (or sites of disease) plus any measurable lesions over and above those 
listed as target lesions are considered non-target lesions. Measurements are not required but these 
lesions should be noted at baseline and should be followed as “present” or “absent”. 
1.1.5 Response 
All patients will have their BEST RESPONSE from the start of study treatment until the end of 
treatment classified as outlined below: 
Complete Response (CR): Disappearance of target and non-target lesions and normalization of 
tumor markers. Pathological lymph nodes must have short axis measures < 10 mm (Note: 
continue to record the measurement even if < 10 mm and considered CR). Residual lesions 
(other than nodes < 10 mm) thought to be non-malignant should be further investigated (by 
cytology or positron emission tomography [PET] scans) before CR can be accepted. To qualify 
as CR, CR must be confirmed by repeat disease assessment studies performed no less than 
4 weeks after the criteria for response were first met to qualify as CR. 
Partial Response (PR): At least a 30% decrease in the sum of measures (longest diameter for 
tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline 
sum of diameters. Non-target lesions must be non-PD. To qualify as PR, PR must be confirmed 
by repeat disease assessment studies performed no less than 4 weeks after the criteria for 
response were first met to qualify as CR. 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD taking as reference the smallest sum of diameters on study. 
Progressive Disease (PD): At least a 20% increase in the sum of diameters of measured lesions 
taking as references the smallest sum of diameters recorded on study (including baseline) AND 
an absolute increase of ≥ 5 mm. Appearance of new lesions will also constitute progressive 
disease (including lesions in previously unassessed areas). In exceptional circumstances, 
unequivocal progression of non-target disease may be accepted as evidence of disease 
progression, where the overall tumor burden has increased sufficiently to merit discontinuation 
of treatment or where the tumor burden appears to have increased by at least 73% in volume. 
Modest increases in the size of 1 or more non-target lesions are NOT considered unequivocal 
progression. If the evidence of PD is equivocal (target or nontarget), treatment may continue 
until the next assessment, but if confirmed, the earlier date must be used. 


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Table 1: 
Integration of Target, Nontarget and New Lesions into Response Assessment 
Target Lesions 
Nontarget Lesions 
New 
Lesions 
Overall 
Response 
Best Response for this  
Category also Requires 
Target Lesions ± Nontarget lesions 
CR 
CR 
No 
CR 
Normalization of tumor markers, tumor 
nodes < 10 mm 
CR 
Non-CR/Non-PD 
No 
PR 
 
CR 
Not all evaluated 
No 
PR 
PR 
Non-PD/ not all 
evaluated 
No 
PR 
SD 
Non-PD/ not all 
evaluated 
No 
SD 
Documented at least once ≥ 6 to 8 weeks 
from baseline 
Not all evaluated 
Non-PD 
No 
NE 
 
PD 
Any 
Any 
PD 
 
Any 
PD 
Any 
PD 
 
Any 
Any 
Yes 
PD 
 
Nontarget lesions ONLY 
No Target 
CR 
No 
CR 
Normalization of tumor markers, tumor 
nodes < 10 mm 
No Target 
Non-CR/non-PD 
No 
Non-
CR/non-PD 
 
No Target 
Not all evaluated 
No 
NE 
 
No Target 
Unequivocal PD 
Any 
PD 
 
No Target 
Any 
Yes 
PD 
 
Note: Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence of 
disease progression at that time should be reported as “symptomatic deterioration”. This is a reason for stopping therapy, but 
is NOT objective PD. Every effort should be made to document the objective progression even after discontinuation of 
treatment. 


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For nonrandomized trials, where confirmation of response is required, best overall response can 
be interpreted as follows: 
Table 2: 
Interpretation of Best Overall Response 
Response:  
First Time Point 
Subsequent  
Time Point 
BEST Overall Response 
Also Requires 
CR 
CR 
CR 
Normalization of tumor 
markers, tumor nodes < 10 mm 
CR 
PR 
SD, PD or PR (see comment*) 
 
CR 
SD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
 
CR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
 
CR 
NE 
SD provided minimum criteria for SD 
duration met, otherwise NE 
 
PR 
CR 
PR 
 
PR 
PR 
PR 
 
PR 
SD 
SD 
 
PR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
 
PR 
NE 
SD provided minimum criteria for SD 
duration met, otherwise NE 
 
NE 
NE 
NE 
 
CR = complete response; NE = not evaluable; PD = progressive disease; PR = partial response; SD = stable disease 
*  
may consider PR providing initial “CR” likely PR on subsequent review – then original CR should be corrected. Recurrence 
of lesion after true CR is PD. 
 
1.2 Response Duration 
Response duration will be measured from the time measurement criteria for CR/PR (whichever 
is first recorded) are first met until the first date that recurrent or progressive disease is 
objectively documented, taking as reference the smallest measurements recorded on study 
(including baseline). 


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1.3 Stable Disease Duration 
Stable disease duration will be measured from the time of start of treatment (or randomization 
for randomized studies) until the criteria for progression are met, taking as reference the smallest 
sum on study (including baseline). 
1.4 Methods of Measurement 
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. Assessments should be identified 
on a calendar schedule and should not be affected by delays in therapy, which may be 
treatment-arm dependent. While on study, all lesions recorded at baseline should have their 
actual measurements recorded at each subsequent evaluation, even when very small (e.g., 2 mm). 
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. For lesions which fragment/split 
add together the longest diameters of the fragmented portions; for lesions which coalesce, 
measure the maximal longest diameter for the “merged lesion”. 
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial 
and ≥ 10 mm diameter as assessed using calipers (e.g., skin nodules). For the case of skin 
lesions, documentation by color photography including a ruler to estimate the size of the lesion is 
suggested. If feasible, imaging is preferred. 
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 
lesions. However, lesions > 20 mm 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 (e.g., for body scans). While PET scans are not 
considered adequate to measure lesions, positron emission tomography-computerized 
tomography [PET-CT] scans may be used providing that the measures are obtained from the CT 
scan and the CT scan is of identical diagnostic quality to a diagnostic CT (with intravenous [iv] 
and oral contrast). 
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. If new lesions are identified by ultrasound in the course of the study, 
confirmation by CT is advised. 


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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 complete response 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 patient to 
be considered in complete response. 
Cytology, 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 (e.g., with certain taxane compounds or angiogenesis 
inhibitors), the cytological confirmation of the neoplastic origin of any effusion that appears or 
worsens during treatment can be considered if the measurable tumor has met criteria for response 
or stable disease in order to differentiate between response (or stable disease) and progressive 
disease. 


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Appendix 6 Immune-Related Response Criteria in Solid Tumors 
Response to treatment will be measured using immune-related response criteria (irRC),1 which 
have been defined for use with immunotherapy.  
To systematically characterize additional patterns of response in patients with advanced 
melanoma, underlying WHO criteria (hereafter referred to as RECIST) formed the basis for 
irRC.  
Antitumor Response Based on Total Measurable Tumor Burden 
For the irRC, only index and measurable new lesions are taken into account (in contrast to 
conventional RECIST, which does not require the measurement of new lesions, nor do they 
include new lesion measurements in the characterization of evolving tumor burden). At the 
baseline tumor, the sum of the products of the 2 largest perpendicular diameters (SPD) of all 
index lesions (5 lesions per organ, up to 10 visceral lesions and 5 cutaneous index lesions) is 
calculated. At each subsequent tumor assessment, the SPD of the index lesions and of new, 
measurable lesions (≥5 x 5 mm; up to 5 new lesions per organ: 5 new cutaneous lesions and 
10 visceral lesions) are added together to provide the total tumor burden: 
Tumor burden = SPDindex lesions + SPDnew, measurable lesions 
Use of tumor burden in irRC criteria is presented in Table A. 
                                               
 
1 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. 


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Table A 
Definitions of Overall Responses 
 
irRC 
New, measurable lesions (i.e., ≥5 x 5 mm) 
Incorporated into tumor burden 
New, nonmeasurable lesions (i.e., <5 x 5 mm) 
Do not define progression (but preclude irCR) 
Non-index lesions 
Contribute to defining irCR  
(complete disappearance required) 
CR 
Disappearance of all lesions in 2 consecutive observations 
not less than 4 weeks apart 
PR 
≥ 50% decrease in tumor burden compared with baseline in 2 
observations at least 4 weeks apart 
SD 
>50% decrease in tumor burden compared with  
baseline cannot be established  
nor 25% increase compared with nadir 
PD 
At least 25% increase in tumor burden compared with nadir 
(at any single time point) in 2 consecutive observations at 
least 4 weeks apart 
CR = complete response; irCR = complete response; irRC = immune-related response criteria; PD = progressive disease;  
PR = partial response; SD = stable disease 
Time Point Response Assessment Using irRC 
Percentage changes in tumor burden per assessment time point describe the size and growth 
kinetics of both conventional and new, measurable lesions as they appear. At each tumor 
assessment, the response in index and new, measurable lesions is defined based on the change in 
tumor burden (after ruling out immune-related progressive disease [irPD]). Decreases in tumor 
burden must be assessed relative to baseline measurements (i.e., the SPD of all index lesions at 
screening). The irRC were derived from RECIST and, therefore, the thresholds of response 
remain the same (Table B). However, the irRC response categories have been modified from 
those of RECIST, as detailed in Tables A and B. 
Table B 
Derivation of Overall Responses Using Immune-Related Response Criteria 
Measurable response 
Nonmeasurable response 
Overall 
response 
Index and new measurable lesions 
(tumor burden),a % 
Nonindex lesions 
New nonmeasurable 
lesions 
Using irRC 
↓100 
Absent 
Absent 
irCRb 
ie 
Stable 
Any 
irPRb 
↓100 
Unequivocal progression 
Any 
irPRb 
↓≥50 
Absent/stable 
Any 
irPRb 
↓≥50 
Unequivocal progression 
Any 
irPRb 
↓<50 to <25↑ 
Absent/stable 
Any 
irSD 
↓<50 to <25↑ 
Unequivocal progression 
Any 
irSD 
≥25? 
Any 
Any 
irPDb 


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↑ = increase in tumor burden; ↓ = decrease in tumor burden; irCR = immune-related complete response; 
irPD = immune-related progressive disease; irPR = immune-related partial response; irRC = immune-related 
response criteria; irSD = immune-related stable disease 
a Decreases assessed relative to baseline, including measurable lesions only (>5 x 5 mm) 
b Assuming response (i.e., irCR) and progression (i.e., irPD) are confirmed by a second, consecutive assessment at 
least 4 weeks apart. 
 
Overall Response Using the irRC 
The overall response according to the irRC is derived from time point assessment (based on 
tumor burden) as follows: 
• irCR, complete disappearance of all lesions (whether measurable or not, and no lesions); 
confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first 
documented 
• irPR, decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive 
assessment at least 4 weeks after first documentation 
• immune-related stable disease (irSD), not meeting criteria for irCR or irPR, in absence of 
irPD 
• irPD, increase in tumor burden ≥25% relative to nadir (minimum recorded tumor 
burden); confirmation by a repeat, consecutive assessment no less than 4 weeks from the 
date first documented 
Patients are considered to have irPR or irSD even if new lesions are present, as long as they met 
the respective thresholds of response described above. Furthermore, patients are not considered 
to have irPD if new lesions are present and the tumor burden of all lesions did not increase by 
≥25%. In contrast to irCR, irPR, and irPD, a response of irSD does not require confirmation. It is 
important to note that irCR, irPR, and irSD include all patients with CR, PR or SD by RECIST 
as well as those patients who shift to these irRC categories from RECIST PD. Patients with irSD, 
particularly those with slow-declining tumor burden ≥25% from baseline at the last tumor 
assessment, are considered clinically meaningful because they show an objectively measurable 
reduction in tumor burden without reaching the 50% threshold that defines irPR (ie, this 
represents an objectively measured reduction not commonly observed in the natural history of 
advanced melanoma patients). 
If a patient is classified as having irPD at a postbaseline tumor assessment, then confirmation of 
irPD by a second scan in the absence of a rapid clinical deterioration is required. The definition 
of confirmation of progression represents an increase in tumor burden ≥25% compared with 
nadir at 2 consecutive time points at least 4 weeks apart. It is recommended that this be done at 
the discretion of the Investigator because follow-up with observation alone may not be 
appropriate for patients with a rapid decline in performance status. Confirmation of irPD allows 
for the capture of all observed responses using the irRC (Table B), as most of these 
late-responding patients have a trend toward response within 4 weeks after initial irPD. Whereas 


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RECIST consider any new measurable lesion to indicate PD, determination of immune-related 
best overall response (irBOR) is based on changes in total tumor burden from baseline (nadir, for 
irPD) tumor assessment, regardless of any initial increase in baseline lesions or the appearance of 
new lesions. 

SAP_001.pdf: 
S T A TI S TI C A L A N A L Y SI S P L A N  
Cli nic al St u d y A R R A Y -3 8 2 -2 0 1  
A P h ase 1 b/ 2 St u d y of A R R Y- 3 8 2 i n C o m bi n ati o n wit h Pe m br oliz u m a b,  
a Pr o gr a m me d Cell De at h Rece pt or 1 ( P D- 1) A nti b o d y, f or t he Tre at me nt of 
P atie nts wit h A d v a nce d S oli d T u m ors  
P R O T O C O L N U M B E R : 
A R R A Y -3 8 2 -2 0 1  
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1. 0  
D A T E:  
2 0  Fe br u ar y  2 0 2 0  
Pre p are d b y:  
 
 
Arra y Bi o P har ma I nc.  
(a w h oll y o w ne d s u bsi di ar y of Pfizer I nc.) 
3 2 0 0 Wal n ut Street  
B o ul der, C O 8 0 3 0 1 
C O N FI D E N TI A L  
T he i nf or m ati o n c o nt ai ne d i n t his d oc u m e nt is re g ar de d as c o nfi de nti al a n d m a y n ot be discl ose d t o 
a n ot her p art y wit h o ut t he per missi o n of t he a ut h or u nless s uc h discl os ure is re q uir e d b y l a w or 
re g ul ati o ns. Pers o ns t o w h o m t he i nf or m ati o n is discl ose d m ust be i nf or m e d t h at t he i nf or m ati o n is 
c o nfi de nti al a n d m a y n ot be f urt her discl ose d b y t he m.  
P P D


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
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Sa m ple Size C o nsi derati o ns  ................................................................................... 1 4 
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S T U D Y E N D P OI N T S  ...................................................................................................... 1 7 
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D ose - Det er mi ni n g Set  ............................................................................................ 2 2 
5. 3  
F ull A nal ysis Set  .................................................................................................... 2 2 
5. 4  
Safet y Set  ............................................................................................................... 2 2 
5. 5  
P har mac o ki netic Set ............................................................................................... 2 2 
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C H A N G E S F R O M T H E S T U D Y P R O T O C O L  ........................................................... 2 3 
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7. 1. 1  
St u d y Dr u g  ........................................................................................... 2 4 
7. 1. 2  
St u d y Trea t me nt ................................................................................... 2 4 
7. 1. 3  
Baseli ne  ................................................................................................ 2 4 
7. 1. 4  
Last C o ntact Date  ................................................................................. 2 4 
7. 1. 5  
Treat me nt Start Dat e  ............................................................................ 2 5 
7. 1. 6  
St u d y Da y ............................................................................................. 2 5 
7. 1. 7  
Re p orti n g C o n ve nti o ns  ........................................................................ 2 5 
7. 1. 8  
U nsc he d ule d Visits  .............................................................................. 2 7 
7. 1. 9  
I m p utati o n R ules f or Partial or Missi n g Dates .................................... 2 7 
7. 2  
Patie nt Dis p ositi o n  ................................................................................................. 3 1 
7. 3  
Pr ot oc ol De viati o ns  ................................................................................................ 3 2 
C C
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De m o gra p hics a n d Pretreat me nt C haracteristics  ................................. 3 2 
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Me dical a n d Disease Hist or y  ............................................................... 3 2 
7. 4. 3  
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7. 4. 5  
Pri or A ntica ncer T hera p y  ..................................................................... 3 3 
7. 4. 6  
Ot her Pri or Me dicati o ns a n d Pr oce d ures  ............................................. 3 4 
7. 5  
Efficac y A nal ysis  ................................................................................................... 3 4 
7. 5. 1  
O bjecti ve Res p o nse Rate  ..................................................................... 3 4 
7. 5. 2  
D urati o n of Res p o nse  ........................................................................... 3 6 
7. 5. 3  
Pr o gressi o n-free S ur vi val ..................................................................... 3 6 
7. 5. 4  
O verall S ur vi val  ................................................................................... 3 7 
7. 5. 5  
I m m u ne-relat e d Res p o ns e Rate ........................................................... 3 7 
7. 5. 6  
I m m u ne-relat e d Pr o gressi o n-free S ur vi v al .......................................... 3 8 
7. 6  
Safet y A nal ysis  ...................................................................................................... 3 8 
7. 6. 1  
E xte nt of St u d y Dr u g E x p os ure  ........................................................... 3 8 
7. 6. 2  
C o nc o mita nt Me dicati o ns  .................................................................... 4 0 
7. 6. 3  
S u bse q ue nt A ntica ncer T hera pies  ........................................................ 4 1 
7. 6. 4  
A d verse E v e nts  .................................................................................... 4 1 
7. 6. 5  
Cli nic al La b orat or y E val uati o ns  .......................................................... 4 3 
7. 6. 6  
Pre g na nc y T ests  ................................................................................... 4 6 
7. 6. 7  
Vital Si g ns a n d B o d y Meas ure me nts  ................................................... 4 6 
7. 6. 8  
E C G ...................................................................................................... 4 7 
7. 6. 9  
P h ysical E xa mi nati o ns  ......................................................................... 4 8 
7. 6. 1 0  
Easter n C o o perati ve O nc ol o g y Gr o u p Perf or ma n ce Stat us 
Perf or ma nce Stat us  .............................................................................. 4 8 
7. 6. 1 1  
Cli nicall y Si g nifica nt Pr oce d ures  ........................................................ 4 8 
7. 6. 1 2  
Tra nsf usi o n  .......................................................................................... 4 8 
7. 7  
P har mac o ki netic A n al ysis  ...................................................................................... 4 8 
7. 7. 1  
Plas ma C o nce ntrati o ns of A R R Y- 3 8 2 a n d its t hree meta b olites 
( A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0 a n d A R 0 0 4 7 0 8 7 0) ................................ 4 8 
7. 7. 2  
Plas ma P har mac o ki netic Para meters f or A R R Y - 3 8 2 a n d its 
t hree meta b olites ( A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0 a n d 
A R 0 0 4 7 0 8 7 0)  ....................................................................................... 4 9 
 
C CI


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A nal ysis .................................................................................................................. 5 2 
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9. 0  
R E F E R E N C E S  ................................................................................................................. 5 4 
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I N S T R U C TI O N S ............................................................................................................. 5 5 
 
C C
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A R R Y- 3 8 Z ( C S F-l R i n hi bit or) 
A R R A Y- 3 8 Z- Z 0l St atisti c al A n al ysis Pl a n 
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V ersi o n 1. 0 
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A R R Y- 3 8 2 ( C S F-I R i n hi bit or) 
A R R A Y- 3 8 2- 2 0 1 St atisti c al A n al ysis Pl a n 
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V ersi o n 1. 0 
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5 
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O oc U UI O 
f 7 6 2l 2 0 S- 1 c 0 7- 4 0 1 b- b 7f 1-l 1 1 d c 3 7 5 3 2 •• 1 


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LI S T  O F  A B B R E VI A TI O N S  
A b bre vi ati o n or S peci al Ter m  
E x pl a n ati o n  
A E  
a d verse e ve nt 
A L K  
a na plastic l y m p h o ma ki nase  
A L P  
al kali ne p h os p hatase  
A L T  
ala ni ne a mi n otra nsferase  
Arra y  
Arra y Bi o P har ma I nc.  
A S T  
as partate a mi n otra nsferase  
A T C  
A nat o mical T hera pe utic C he mical  
A U C  
area u n der t he plas ma c o nce ntrati o n -ti me cur ve  
A U C 0- x 
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m zer o t o t he s pecifie d ti me 
p oi nt  
A U C last 
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m zer o t o t he last meas ura ble 
ti me p oi nt 
A U C ta u 
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve o ver t he d osi n g i nter val  
B L Q  
bel o w t he li mit of q ua nti ficati o n 
B P  
bl o o d press ure  
B R A F  
B- R A F pr ot o -o nc o ge ne, seri ne/t hre o ni ne -pr otei n ki nase  
C 1 D 1  
Da y 1 of C ycle 1  
C X D Y 
Da y Y of C ycle X 
CI  
c o nfi de nce i nter val 
C K  
creati ne ki nase 
C ma x  
o bser ve d ma xi m u m plas ma c o nce ntrati o n  
C R  
c o m plete res p o nse  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
ct D N A  
circ ulati n g t u m or D N A 
C tr o u g h 
tr o u g h ( pre d ose) c o nce ntrati o n at stea d y state  
C V  
c oefficie nt of variati o n  
D C R  
disease c o ntr ol rate  
D O R  
d urati o n of res p o nse  
D R L  
Dr u g Refere nce Listi n g  


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E C G  
electr ocar di o gra m 
E C H O  
ec h ocar di o gra m 
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
e C R F  
electr o nic case re p ort f or m 
E D C  
electr o nic data ca pt ure 
E G F R  
e pi der mal gr o wt h fact or rece pt or  
E O T  
e n d of treat me nt 
F A  
fl u orescei n a n gi o gra p h y 
F A S  
f ull a nal ysis set 
F D A  
U nite d States  F o o d a n d Dr u g A d mi nistrati o n  
I C F 
i nf or me d c o nse nt f or m 
K M  
Ka pla n -Meier  
L F T  
li ver f u ncti o n test 
L L O Q  
L o wer li mit of q ua ntificati o n  
L V E F  
left ve ntric ular ejecti o n fracti o n 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
M R
C ma x  
rati o of C ma x  val ues of t he meta b olite c o m pare d t o pare nt, c orrecte d f or m olec ular 
wei g ht  
M R
A U Clast  
rati o  of  A U C last val ues  of  t he  meta b olite  c o m pare d  t o  pare nt,  c orrecte d  f or  
m olec ular wei g ht  
ms  
millisec o n d(s)  
M U G A  
m ulti -gate d ac q uisiti o n  
N C A  
n o nc o m part me ntal a nal ysis  
N CI  
Nati o nal Ca ncer I nstit ute  
N S C L C  
n o n -s mall cell l u n g ca ncer 
O C T  
O ptical C o here nce T o m o gra p h y  
O R R  
o bjecti ve res p o nse rate  
O S  
o verall s ur vi val  
P D  
pr o gressi ve disease  
P D - 1 
pr o gra m me d cell deat h pr otei n 1  
P D -L 1  
pr o gra m me d cell deat h pr otei n li ga n d 1  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
Versi o n 1. 0  
8 
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
A b bre vi ati o n or S peci al Ter m  
E x pl a n ati o n  
P F S  
pr o gressi o n -free s ur vi val 
P K  
p har mac o ki netic(s)  
P K S  
P K set  
P P S  
P er-pr ot oc ol set  
P R  
partial res p o nse  
P T  
preferre d ter m  
Q T  
Q T i nter val  
Q Tc  
Q T i nter val c orrecte d f or heart rate  
Q Tc F  
Q T i nter val c orrecte d f or heart rate usi n g Fre dericia’s f or m ula  
R A U C  
acc u m ulati o n rati o base d o n A U C val ues  
R B C  
re d bl o o d cell(s) 
R E CI S T v 1. 1  
Res p o nse E val uati o n Criteria i n S oli d T u m ors versi o n 1. 1  
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n  
S D  
sta ble disease 
SI u nits  
I nter nati o nal S yste m of U nits 
S O C  
s yste m or ga n class 
S O P  
sta n dar d o perati n g pr oce d ure 
S S  
safet y set 
T B L  
t otal bilir u bi n 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt 
T E S A E  
treat me nt-e mer ge nt seri o us a d verse e ve nt 
T last 
o bser ve d ti me of last meas ure d c o nce ntrati o n 
T ma x  
o bser ve d ti me of C ma x  
U L N  
u p per li mit of n or mal  
W B C  
w hite bl o o d cell(s)  
W H O  
W orl d Healt h Or ga nizati o n  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
Versi o n 1. 0  
9 
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
1. 0  
I N T R O D U C TI O N 
T his d oc u me nt descri bes t he statistical a nal yses a n d data prese ntati o ns t o be perf or m e d f or t he 
cli nical pr ot oc ol A R R A Y - 3 8 2-2 0 1 e ntitle d “ A P hase 1 b/ 2 St u d y of A R R Y-3 8 2 i n C o m bi nati o n 
wit h Pe m br oliz u ma b, a Pr o gra m me d Cell D eat h R ece pt or 1 ( P D -1) A nti b o d y, f or t he Treat me nt of 
Patie nts wit h A d va nce d S oli d T u m ors ”.  
T his statistical a nal ysis pla n (S A P ) s h o ul d be rea d i n c o nj u ncti o n wit h t he st u d y pr ot oc ol a n d 
electr o nic case re p ort f or m s  (eC R F s). T his d oc u me nt has bee n de vel o pe d usi n g t he pr ot oc ol 
Versi o n  5 date d 0 2 Ja n uar y 2 0 1 9 a n d e C R Fs date d 1 3  J u ne  2 0 1 8. A n y f urt her c ha n g es t o t he 
pr ot oc ol or e C R F s ma y necessitate u p d ates t o t he S A P.  
T his  S A P  pr o vi des  a  c o m pre he nsi ve  a n d  detaile d  descri pti o n  of  t he  strate g y,  rati o nale  a n d  
statistical tec h ni q ues t o be use d t o assess t he safet y, efficac y, p har mac o ki n etics  ( P K) 
 
a nal yses i n a d ult patie nts wit h selecte d a d v a nce d s oli d t u m ors ( Part A/ P hase 1 b); i n a d ult patie nts 
wit h a d va nce d s oli d t u m ors t hat ha ve pr o gresse d o n pri or P D - 1/ P D-L 1 i n hi bit ors,  i n a d ult patie nts 
wit h 
plati n u m- resista nt  o varia n  ca ncer  (pr O V C A ) a n d  i n  patie nts  wit h  pa ncreatic  d uctal  
a de n ocarci n o ma (P D A ) ( P hase 2). T he p ur p ose of t his S A P is t o e ns ure t he cre di bilit y of t he st u d y 
fi n di n gs b y s pecif yi n g t he statistical a p pr oac h es f or t he fi nal a nal ysis of st u d y data. T his S A P will 
be fi nalize d a n d si g ne d pri or t o t he cli nical data b ase l oc k .  
Statistical a nal yses detaile d i n t his S A P will be c o n d ucte d usi n g S A S ® , Versi o n 9. 4 or hi g her ( S A S 
I nstit ute, I nc., Car y, N C U S A). N o nc o m part me nt al P K a nal yses will be perf or me d wit h P h oe ni x®  
Wi n N o nli n
®  Ve r s i o n  8. 0 or  hi g her  ( Certara  U S A,  I nc.,  Pri ncet o n,  NJ).  Ori gi nal  sa m ple  size  
calc ulati o ns f or P has e 2 were c o n d ucte d usi n g R, Versi o n 3. 4. 3. 
1. 1  
Re s p o nsi bilities 
A n Arra y or C R O -desi g n ate d Bi ostatisticia n or Statistical Pr o gra m mer will perf or m a n y statistical 
a nal yses r e q uire d f or p atie nt dis p ositi o n, pr ot oc ol de viati o ns, patie nt c h aracteristics, effic ac y a n d 
safet y; a n Arr a y or C R O-desi g nate d Bi ostatisticia n is res p o nsi ble f or t he pr o d ucti o n a n d q ualit y 
c o ntr ol  of  all  ta bles,  fi g ures  a n d  listi n gs  ass oci ate d  wit h  t hese  a n al yses.  A n  Arra y  or  C R O -
desi g nate d Cli nical P har mac ol o g y re prese ntati ve will perf or m a n y P K statistical a nal yses a n d  is 
res p o nsi ble f or t he pr o d u cti o n a n d q ualit y c o ntr ol of all ta bles, fi g ures a n d listi n gs ass ociate d wit h 
t hese a nal yses. A n Arr a y Tra nslati o n Scie nce re prese ntati ve will perf or m a n y 
 statistical 
a nal yses  a n d is r es p o nsi ble f or t h e pr o d u cti o n a n d q ualit y c o ntr ol  of all ta bl es, fi g ures a n d listi n gs 
ass ociate d wit h t hese a nal yses.  
C CI
C CI


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 0  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
2. 0  
S T U D Y O B J E C TI V E S  
2. 1  
Pri m ar y O bjecti ve  
P hase 1 b/ Part A:  
•  To deter mi ne t he ma xi m u m t olerate d d ose ( M T D) a n d/ or rec o m me n de d P hase 2 d ose 
( R P 2 D) of A R R Y-3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b i n patie nts wit h selecte d 
s oli d t u m ors 
P hase 2: P D - 1 or P D- L 1 I n hi bit or Refract or y:  
•  To esti mate t he efficac y of A R R Y - 3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b i n patie nts 
wit h  a d va nce d  s oli d  t u m ors  f oll o wi n g  pr o gressi o n  o n  pri or  P D - 1/ P D-L 1  i n hi bit or  
t hera p y 
P has e 2: Plati n u m -resista nt O varia n Ca ncer: 
•  To esti mate t he efficac y of A R R Y - 3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b i n patie nts 
wit h micr osatellite sta ble ( M S S)/ mis matc h re pair ( M M R) -pr oficie nt pl ati n u m -resista nt 
o varia n ca ncer ( pr O V C A) 
P hase 2: Pa ncreatic D uct al A de n o carci n o ma:  
•  To esti mate t he efficac y of A R R Y - 3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b i n patie nts 
wit h M S S/ M M R -pr oficie nt pa ncreatic d uctal a d e n ocarci n o ma ( P D A)  
2. 2  
Sec o n d ar y O bjecti ves  
P hase 1 b/ Part A:  
•  To  descri be  t he  preli mi nar y  a ntit u m or  acti vit y  of  t he  c o m bi nati o n  base d  o n  t he  
Res p o nse Criteria I n S oli d T u m ors, versi o n 1. 1 ( R E CI S T v 1. 1) 
•  To descri be t h e preli mi nar y a ntit u m or acti vit y of t he c o m bi nati o n base d o n i m m u ne -
relate d r es p o nse criteria (ir R C) 
•  To c haract erize t he s afet y a n d t olera b ilit y of t he c o m bi nati o n, i ncl u di n g ac ute a n d 
c hr o nic t o xicities  
•  To  e val uate  t he  p har mac o ki netics  ( P K)  of  A R R Y -3 8 2  i n  c o m bi nati o n  wit h  
pe m br oliz u ma b 
P hase 2: P D - 1 or P D- L 1 I n hi bit or Refract or y:  
•  To f urt her esti mate t he efficac y of t he c o m bi nati o n  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 1  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•  To esti mate t he efficac y of t he c o m bi nati o n, as assesse d b y c ha n g es i n t u m or mar k ers 
fr o m baseli ne 
•  To c haract erize t he s afet y a n d t olera bilit y of t he c o m bi nati o n, i ncl u di n g ac ute a n d 
c hr o nic t o xicities  
•  To e val uate t he P K of A R R Y - 3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b 
P hase 2: Plati n u m- resista nt O varia n Ca ncer:  
•  To  f urt her  esti mate  t h e  efficac y  of  t he  c o m bi nati o n  i n  patie nts  wit h  M S S/ M M R -
pr oficie nt pr O V C A 
•  To esti mate t he efficac y of t he c o m bi nati o n, as assesse d b y c ha n g es i n t u m or mar k ers 
fr o m baseli ne  
•  To c haract erize t he s afet y a n d t olera bilit y of t he c o m bi nati o n, i ncl u di n g ac ute a n d 
c hr o nic t o xicities  
•  To e val uate t he P K of A R R Y - 3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b 
P hase 2: Pa ncreatic D uct al A de n o carci n o ma:  
•  To  f urt her  esti mate  t h e  efficac y  of  t he  c o m bi nati o n  i n  patie nts  wit h  M S S/ M M R -
pr oficie nt P D A 
•  To c haract erize t he s afet y a n d t olera bilit y of t he c o m bi nati o n, i ncl u di n g ac ute a n d 
c hr o nic t o xicities  
•  To e val uate t he P K of A R R Y - 3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
C C
I


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 2  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 3  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
3. 0  
I N V E S TI G A TI O N A L P L A N 
3. 1  
O ver all St u d y Desi g n a n d Pl a n  
T his is a n o p e n -la bel, m ultice nter P hase 1 b/ 2 st u d y t o deter mi ne t he M T D a n d/ or R P 2 D of A R R Y-
3 8 2 i n c o m bi nati o n wit h pe m br oliz u ma b i n a d ult patie nts wit h selecte d a d va nce d s oli d t u m ors 
( Part A/ P hase 1 b); a n d t o esti mate t he efficac y of t he c o m bi nati o n i n patie nts wit h a d va nce d s oli d 
t u m ors t hat ha ve pr o gr esse d o n pri or P D- 1/ P D-L 1 i n hi bit ors, i n patie nts wit h pr O V C A a n d i n 
pati e nts wit h P D A ( P hase 2). 
P hase 1 b/ Part A:  
Part A i ncl u des a d ose-es calati o n c o m p o ne nt wit h 2  pla n ne d d ose c o h orts ( 2 0 0 m g o nce dail y [ Q D] 
a n d  4 0 0  m g  Q D).  Or al  d oses  of  A R R Y-3 8 2  will  be  a d mi nistere d  Q D  i n  c o m bi nati o n  wit h  
pe m br oliz u ma b 2  m g/ k g i ntra ve n o usl y (i v) e ver y 3 wee ks ( Q 3 W). Patie nts i n C o h ort 1 will be 
e nr olle d o n a r olli n g basis u p t o 6  e val ua ble pati e nts or u ntil D L Ts are o bser ve d i n m ore t ha n 
1 patie nt d uri n g C ycle 1. If fe wer t ha n 2 of 6  patie nts e x perie nce a D L T d uri n g C ycle 1, patie nts 
i n C o hort 2 will recei ve A R R Y-3 8 2 4 0 0 m g Q D. If 2 or m ore patie nts i n C o h ort  1 e x perie nce D L Ts 
d uri n g  C ycle  1,  t h e  d osa ge  of  A R R Y-3 8 2  i n  C o h ort  2  will  be  1 0 0  m g  Q D.  If  a  Gra d e  3 
i m m u ne-relate d a d vers e e ve nt (ir A E) (first occ urre nce) is re p orte d i n a gi ve n c o h ort, e nr oll me nt 
i n t hat c o h ort will c o nti n ue at t h e sa me d ose u ntil t he t o xicit y is e v al uate d. If a sec o n d Gra d e 3 
ir A E is r e p orte d or a first Gra de 3 ir A E is re p orte d i n a d diti o n t o a pre vi o us D L T i n a gi ve n c o h ort, 
e nr oll me nt of n e w p atie nts i n t hat c o h ort will be st o p pe d u ntil t he Gra d e 3 ir A E is e v al uate d. If t he 
e ve nt is n ot a D L T ( as d eter mi ne d b y t he I n vesti gat ors i n c o ns ultati o n wit h t he S p o ns or), t h e n 
e nr oll me nt ma y be res u me d, or t he c o h ort ma y be e x pa n de d t o i ncl u de u p t o 9  patie nts. If t he Gra de 
3 ir A E is dee me d a D L T, t he M T D has bee n ac hie ve d a n d a d diti o nal patie nts will be e nr olle d at 
t he pre vi o us d ose le vel or at a n i nter me diat e d ose le vel. 
I nter me diate d os es a n d d oses hi g her t ha n 4 0 0 m g Q D ma y als o be c o nsi dere d u p o n re vie w of t h e 
safet y a n d P K res ults fr o m t he pla n ne d d ose c o h orts. I n t he a bse nce of i de ntificati o n of a n M T D, 
a d ose of 4 0 0  m g or l o w er ma y b e selecte d as t h e R P 2 D as l o n g as t he D L T rate is <  3 3 % (e. g., 
fe wer t ha n 2 of 6 p atie nts e x perie n ce a D L T).  
Part A has bee n c o m plete d a n d t h e M T D/ R P 2 D of A R R Y-3 8 2 was deter mi ne d t o be 3 0 0 m g Q D 
i n c o m bi nati o n wit h pe m br oliz u ma b.  
P hase 2  
T he P hase 2 part  will c o nsist of 3 se parate c o h orts of patie nts. T he P hase 2 P D- 1/ P D- L 1 I n hi bit or 
Refract or y c o h ort will c o nsist of patie nts wit h a d va nce d s oli d t u m ors w h o pr o gresse d o n a P D -
1/ P D- L 1 i n hi bit or -c o ntai ni n g re gi me n as t heir m ost rece nt pri or li ne of t hera p y are w h o are naï ve 
t o pri or C S F-1 R or C S F -1 i n hi bit ors. T he P hase 2 pr O V C A a n d P D A c o h orts will c o nsist of 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 4  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
patie nts wit h pr O V C A a n d patie nts wit h P D A, res pecti vel y, w h o ha v e h a d at least o ne pri or li ne 
of t hera p y a n d w h o are n aï ve t o pri or c hec k p oi nt i n hi bit or ( C PI) t hera p y a n d t o pri or C S F -1 R or 
C S F - 1 i n hi bit ors.  
I n P hase 2, at baseli ne, s u b missi o n of arc hi v e d t u m or tiss ue fr o m t he most rece nt sa m ple c ollecti o n 
a vaila ble or a fr es h  bi o ps y will be re q uire d.  
All patie nts i n P hase 2 will recei ve A R R Y - 3 8 2 at 3 0 0 m g Q D, t he M T D/ R P 2 D deter mi ne d d uri n g 
Part A, i n c o m bi nati o n wit h pe m br oliz u ma b 2 0 0 m g i v Q 3 W . 
Efficac y ass ess me nts i ncl u de det er mi nati o n of o bj ecti ve res p o nse usi n g R E CI S T v 1. 1. F or patie nts 
w h o ha ve i nitial e vi de nce of ra di ol o gical pr o gressi ve disease ( P D) b y R E CI S T v 1. 1, it will be at 
t he discreti o n of t he I n vesti gat or t o kee p  a patie nt o n st u d y treat me nt or  t o st o p st u d y treat me nt 
u ntil re peat i ma gi n g is p erf or me d a p pr o xi matel y 4 wee ks  later i n or der t o c o nfir m P D per ir R C. 
Patie nts wit h c o nfir me d ir P D s h o ul d disc o nti n ue treat me nt. Patie nts wit h a decli ni n g Easter n 
C o o perati ve O n c ol o g y Gr o u p perf or ma n ce stat us ( E C O G P S ), deteriorati n g cli nical s y m pt o ms or 
ra pi d pr o gressi o n of disease/ pr o gressi o n at critical a nat o mical sites (i.e., ce ntral ner v o us s yste m 
[ C N S]) s h o ul d be c o nsi d ere d f or treat me nt disc o nti n uati o n base d   o n cli nical j u d g me nt. 
 
 
 
 
P har mac o ki netic assess me nts i ncl u de deter mi nati o n of plas ma c o n ce ntrati o ns of A R R Y -3 8 2 a n d 
its meta b olites. 
Safet y assess me nts i ncl u de m o nit ori n g of A Es, cli nical la b orat or y tests ( h e mat ol o g y, c oa g ulati o n, 
cli nical  c he mistr y,  t h yr oi d  pa nel,  a n d  uri nal ysis),  p h ysical  e xa mi nati o ns,  vital  si g ns,  a n d  
electr ocar di o gr a ms ( E C Gs). E C O G P S will als o be assesse d.  
3. 2  
S a m ple Size C o nsi der ati o ns  
O verall, a p pr o xi matel y  9 0 patie nts are pla n n e d f or e nr oll me nt. 
F or Part A, t he sa m ple size of a p pr o xi mat el y 1 8 e v al ua ble patie nts (i.e., 6 t o 9 patie nts i n eac h d ose 
c o h ort) is sta n dar d f or p ur p oses of d eter mi ni n g t he M T D a n d R P 2 D. Patie nts will be c o nsi dere d 
e val ua ble if t he y r ecei ve at least 6 7 % of pr ot oc ol -s pecifie d d oses of A R R Y- 3 8 2 d uri n g C ycle 1 or 
ha ve a n a d vers e e ve nt ( A E) or ot her e ve nt as descri be d i n Pr ot oc ol Secti o n 9. 3 . T he bi n o mial 
pr o ba bilities of o bser vi n g a D L T i n a c o h ort of 6 a n d 9 patie nts, ass u mi n g a tr ue rat e of 3 3 %, are 
pr o vi de d i n Ta ble 1  a n d Ta ble 2,  res p ecti vel y. 
 
C CI


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 5  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
T a ble 1: 
Bi n o mi al Pr o b a bilities of D ose - Li miti n g T o xicit y i n a C o h ort of 6 P atie nts 
 
Bi n o mi al Pr o b a bilit y  
K 
E x actl y k D L Ts  
≤ k D L Ts  
> k D L Ts  
0 
0. 0 8 7 8  
0. 0 8 7 8  
0. 9 1 2 2  
1 
0. 2 6 3 4  
0. 3 5 1 2  
0. 6 4 8 8  
2 
0. 3 2 9 2  
0. 6 8 0 4  
0. 3 1 9 6  
3 
0. 2 1 9 4  
0. 8 9 9 8  
0. 1 0 0 2  
4 
0. 0 8 2 3  
0. 9 8 2 1  
0. 0 1 7 9  
5 
0. 0 1 6 5  
0. 9 9 8 6  
0. 0 0 1 4  
6 
0. 0 0 1 4  
1. 0 0 0 0  
0. 0 0 0 0  
     D L T = d ose -li miti n g t o xicit y; k = n u m b er of d ose-li miti n g t o xicities 
T a ble 2: 
Bi n o mi al Pr o b a bilities of D ose - Li miti n g T o xicit y i n a C o h ort of 9 P atie nts  
 
Bi n o mi al Pr o b a bilit y  
K 
E x actl y k D L Ts  
≤ k D L Ts  
> k D L Ts  
0 
0. 0 2 6 0  
0. 0 2 6 0  
0. 9 7 4 0  
1 
0. 1 1 7 1  
0. 1 4 3 1  
0. 8 5 6 9  
2 
0. 2 3 4 1  
0. 3 7 7 2  
0. 6 2 2 8  
3 
0. 2 7 3 1  
0. 6 5 0 3  
0. 3 4 9 7  
4 
0. 2 0 4 8  
0. 8 5 5 2  
0. 1 4 4 8  
5 
0. 1 0 2 4  
0. 9 5 7 6  
0. 0 4 2 4  
6 
0. 0 3 4 1  
0. 9 9 1 7  
0. 0 0 8 3  
7 
0. 0 0 7 3  
0. 9 9 9 0  
0. 0 0 1 0  
8 
0. 0 0 0 9  
0. 9 9 9 9  
0. 0 0 0 1  
9 
0. 0 0 0 1  
1. 0 0 0 0  
0. 0 0 0 0  
      D L T = d ose -li miti n g t o xicit y; k = n u m b er of d ose-li miti n g t o xicities 
F or t he P hase  2  P D - 1/ P D-L 1  I n hi bit or  Refract or y  c o h ort , t he sa m ple  size  of  a p pr o xi matel y  
2 0 patie nts  will  be  e v al uate d  f or  i nitial  e vi de n ce  of  acti vit y  i n  t his  P D - 1/ P D-L 1  refract or y  
p o p ulati o n. 
F or t he P hase 2 pr O V C A c o h ort, a Si m o n’s 2 -sta ge o pti mal desi g n (Si m o n 1 9 8 9 ) will be use d i n 
t he M S S/ M M R-pr oficie nt pr O V C A p o p ulati o n. T he n ull h y p ot hesis o f t he tr ue res p o nse rate is 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 6  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
1 5 % will be t este d at o n e-si de d t y pe I err or rate of 1 0 %. T he alter n ati ve h y p ot hesis is t he tr ue 
res p o nse rat e is at least 3 5 %. Accr ual of patie nts i n Sta ge 1 will c o nti n ue u ntil 9 e val ua ble 
M S S/ M M R - pr oficie nt patie nts ha ve bee n e nr olle d, wit h e val ua ble defi ne d as ha vi n g recei ve d at 
least o ne d os e of st u d y dr u g. T he a nal ysis f or Sta g e 1 will n ot occ ur u ntil all e val ua ble  patie nts i n 
Sta ge 1 ha ve ha d t he o p p ort u nit y t o ha ve at least 2  p ost-baseli ne t u m or assess me nts ( or ha ve 
disc o nti n ue d t u m or assess me nts bef ore ha n d). If t here are fe wer t ha n 2 res p o n ders i n t hese 9 
patie nt s, e nr oll me nt i nt o t his c o h ort of t he st u d y will be st o p pe d. Ot her wise, 1 4 a d diti o nal patie nts 
will  be accr ue d d uri n g Sta ge 2, f or a t otal of 2 3 patie nts e nr olle d i n t his c o h ort. T he n ull h y p ot hesis 
will be rej ecte d if 6 or m ore r es p o nses are o bser v e d i n 2 3 patie nts. Wit h t his s a m ple size, t he act ual 
Ty pe I err o r is 9. 9 %, a n d t he p o wer is 8 0 %. If t he n ull h y p ot hesis is tr ue, t he e x pecte d sa m ple size 
is 1 5 patie nts, a n d t he pr o ba bilit y of st o p pi n g e nr oll me nt i nt o t his c o h ort of t he st u d y earl y is 6 0 %. 
Patie nts w h o ar e M SI -H/ mis matc h re pair -defi cie nt ( d M M R) will n o t be i n cl u de d i n t he Si m o n’s 
2- sta ge a n al yses a n d t h e st u d y will e ns ure t hat t he sa m ple size re q uire me nts are met b y e nr olli n g 
t he re q uire d n u m b er of M S S/ M M R- pr oficie nt pr O V C A patie nts. 
F or t he P hase 2 P D A c o h ort, a Si m o n’s 2 -sta ge o pti mal desi g n ( Si m o n 1 9 8 9) will be use d i n t he 
M S S/ M M R - pr oficie nt P D A p o p ulati o n. T he n ull h y p ot hesis of t he tr ue res p o nse rate is 4 %, vers us 
alter nati ve  of  1 5 %.  A ccr ual  of  patie nts  i n  Sta ge  1  will  c o nti n ue  u ntil  1 5  e val ua ble  
M S S/ M M R - pr oficie nt patie nts ha ve bee n e nr olle d, wit h e val ua ble defi ne d as ha vi n g recei ve d at 
least o ne d os e of st u d y dr u g. T he a nal ysis f or Sta g e 1 will n ot occ ur u ntil all e val ua ble  patie nts i n 
Sta ge 1 ha ve ha d t he o p p ort u nit y t o ha ve at least 2  p ost- baseli ne t u m or assess me nts   (or ha ve 
disc o nti n ue d t u m or assess me nts bef ore h a n d) . If t here are n o res p o n ders i n t hese 1 5 patie nts, 
e nr oll me nt i nt o t his c o h ort of t h e st u d y will be st o p pe d. Ot her wise, 1 4 a d diti o nal M S S/ M M R -
pr oficie nt patie nts will be accr u e d d uri n g Sta ge 2, f or a t otal of 2 9 patie nts e nr olle d i n t his c o h ort. 
T he n ull h y p ot hesis will be rejecte d if 3 or m ore res p o ns es are o bs er ve d i n 2 9  M S S/ M M R -
pr oficie nt patie nts. Wit h t his sa m ple size, t he act ual Ty pe I err or is 9. 9 %, a n d t he p o wer is 8 0 %. If 
t he n ull h y p ot hesis is tr ue, t he e x pecte d sa m ple si ze is 2 1 patie nts, a n d t he pr o ba bilit y of st o p pi n g 
e nr oll me nt i nt o t his c o h ort  of t he st u d y earl y is 5 4 %. P D A p atie nts w h o are M SI -H/ d M M R  will 
n ot be i ncl u de d i n t he Si m o n’s 2 -sta ge a n al yses a n d t he st u d y will e ns ure t hat t he sa m ple size 
re q uire me nts are met b y e nr olli n g t he re q uire d n u m ber of M S S/ M M R - pr oficie nt P D A patie nts.  
 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 7  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
4. 0  
S T U D Y E N D P OI N T S  
4. 1  
Pri m ar y E n d p oi nt  
P hase 1 b/ Part A:  
•  I nci de nce of d ose li miti n g t o xicit y  (D L T ), as a f u n cti o n of t he d ose of A R R Y-3 8 2 w he n 
a d mi nistere d i n c o m bi nati o n wit h pe m br oliz u ma b  
P hase 2: P D - 1 or P D- L 1 I n hi bit or Refract or y:  
•  O bjecti ve res p o ns e rat e ( O R R ), per R E CI S T v 1. 1, as deter mi ne d b y t he I n vesti gat or 
P hase 2 : Plati n u m-resista nt O varia n Ca ncer: 
•  O R R, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat or 
P hase 2: Pa ncreatic D uct al A de n o carci n o ma:  
•  O R R, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat or 
4. 2  
Sec o n d ar y E n d p oi nt s 
P hase 1 b/ Part A:  
•  O R R, as deter mi ne d b y t he I n vesti gat or 
•  D urati o n of res p o ns e ( D O R), as deter mi ne d b y t h e I n vesti gat or 
•  Pr o gressi o n-fr ee s ur vi val ( P F S), as deter mi ne d b y t he I n vesti gat or 
•  O verall s ur vi val ( O S )  
•  I m m u ne-relat e d res p o ns e (ir R R), as deter mi ne d b y t he I n vesti gat or 
•  I m m u ne-relat e d pr o gr essi o n-free s ur vi val (ir P F S), as deter mi ne d b y t he I n v esti gat or 
•  Ty pe,  fr e q ue n c y,  a n d  se verit y  of  A Es,  usi n g  t h e  Nati o nal  Ca n cer  I nstit ute  ( N CI)  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E v e nts ( C T C A E) 
•  Seri o us a d verse e ve nts ( S A Es), usi n g t he N CI C T C A E 
•  Cli nical la b orat or y val ues 
•  Vital si g ns  
•  Plas ma c o nce ntr ati o n -ti me pr ofiles  
•  P K para meters ( e. g., area u n der t he plas ma c o nce ntrati o n -ti me c ur ve o ver t he d osi n g 
i nter val [ A U Cτ], ma xi m u m o bser ve d plas ma c o n ce ntrati o n [ C ma x ], ti me of ma xi m u m 
o bser ve d plas ma c o nce ntrati o n [ T ma x ], plas ma c o nce ntrati o n meas ure d j ust bef ore t h e 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 8  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
ne xt d ose of st u d y dr u g [ C tr o u g h], acc u m ulati o n rati o, a n d meta b olite- t o-p are nt rati o) 
f or A R R Y- 3 8 2 a n d its meta b olites, A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0, a n d A R 0 0 4 7 0 8 7 0 
P ha se 2: P D- 1 or P D- L 1 I n hi bit or Refract or y:  
•  D O R, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat or 
•  P F S, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat or 
•  ir R R, per ir R C, as deter mi ne d b y t he I n v esti gat or 
•  ir P F S, per ir R C, as deter mi ne d b y t he I n v esti gat or  
•  O S   
•  T y pe, fre q u e nc y, a n d se v erit y of A Es, usi n g t he N CI C T C A E 
•  S A Es, usi n g t he N CI C T C A E  
•  Cli nical la b orat or y val ues 
•  Vital si g ns  
•  Plas ma c o nce ntr ati o n -ti me pr ofiles  
•  P K para meters (e. g., A U C τ, Cma x , Tma x , Ctr o u g h, acc u m ulati o n rati o, a n d meta b olite -
t o-pare nt r ati o) f or A R R Y - 3 8 2 a n d its meta b olites, A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0, a n d 
A R 0 0 4 7 0 8 7 0   
P hase 2: Plati n u m- resista nt O varia n Ca ncer: 
•  D O R, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat or  
•  P F S, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat o r 
•  ir R R, per ir R C, as deter mi ne d b y t he I n v esti gat or 
•  ir P F S, per ir R C, as deter mi ne d b y t he I n v esti gat or  
•  O S   
•  C ha n ges fr o m bas eli ne i n rele va nt t u m or mar k ers  
•  Ty pe, fr e q ue nc y, a n d s e v erit y of A Es, usi n g t he N CI C T C A E  
•  S A Es, usi n g t he N CI C T C A E 
•  Cli nical la b orat or y val ues 
•  Vital si g ns  
•  Plas ma c o nce ntr ati o n -ti me pr ofiles 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
1 9  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•  P K para meters (e. g., A U C τ, Cma x , Tma x , Ctr o u g h, acc u m ulati o n rati o, a n d meta b olite-
t o-pare nt r ati o) f or A R R Y - 3 8 2 a n d its meta b olites, A R 0 0 4 6 9 0 9 9 , A R 0 0 4 6 9 1 0 0  a n d 
A R 0 0 4 7 0 8 7 0 
P hase 2: Pa ncreatic  D uct al A de n o carci n o ma:  
•  D O R, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat or 
•  P F S, per R E CI S T v 1. 1, as deter mi ne d b y t he I n v esti gat or 
•  ir R R, per ir R C, as deter mi ne d b y t he I n v esti gat or  
•  ir P F S, per ir R C, as deter mi ne d b y t he I n v esti gat or 
•  O S  
•  T y pe, fre q u e nc y, a n d se v erit y of A Es, usi n g t he N CI C T C A E 
•  S A Es, usi n g t he N CI C T C A E  
•  Cli nical la b orat or y val ues 
•  Vital si g ns  
•  Plas ma c o nce ntr ati o n -ti me pr ofiles  
•  P K para meters (e. g., A U C τ, Cma x , Tma x , Ctr o u g h, acc u m ulati o n rati o, a n d meta b olite-
t o-pare nt r ati o) f or A R R Y - 3 8 2 a n d its meta b olites, A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0, a n d 
A R 0 0 4 7 0 8 7 0 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C C
I


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
2 0  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI
C
C
I


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
2 1  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C
C
I


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
2 2  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
5. 0  
A N A L Y SI S S E T S  
5. 1  
Scree ne d  
Scree ne d p atie nts i ncl u de all patie nts w h o si g n t he I nf or me d C o nse nt F or m (I C F). 
5. 2  
D ose -Deter mi ni n g Set  
T he d ose- deter mi ni n g  set ( D D S) i ncl u des all patie nts i n P hase 1 b w h o recei ve at l east 6 7 % of t he 
pla n ne d c u m ulati ve d ose of A R R Y - 3 8 2 d uri n g C ycle 1 or disc o nti n ue t he treat me nt b eca use of 
D L T .  
5. 3  
F ull A n al ysis Set  
T he full a nal ysis set ( FA S ) will i ncl u de all patie nts w h o ha ve r ecei ve d at l east 1 d ose ( partial or 
f ull) of A R R Y-3 8 2 or pe m br oliz u ma b . T he F A S will be use d f or t he s u m mar y of de m o gra p hics, 
baseli ne c haracteristics, patie nt dis p ositi o n data , a n d all efficac y a nal yses.  
5. 4  
S afet y Set  
T he safet y set ( S S) i ncl u des all patie nts w h o recei ve at least 1 d ose ( partial or f ull) of A R R Y- 3 8 2 
or pe m br oliz u ma b. T he S S is t he sa me as t he F A S i n t his st u d y. 
U nless ot her wise s pecifie d, t he S S will be t he defa ult a nal ysis set use d f or all safet y a nal yses.  
5. 5  
P h ar m ac o ki netic Set  
T he p har m ac o ki netic s et (P K S ) i ncl u des all p atie nts fr o m S S w h o ha ve recei ve d a n y acti ve st u d y 
treat me nt ( A R R Y-3 8 2), wit h at least o n e p ost -d os e bl o o d dra w t o d eter mi n e plas ma c o nce ntrati o n 
of A R R Y-3 8 2 a n d its meta b olites ( A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0 a n d  A R 0 0 4 7 0 8 7 0), a n d w h o ha v e 
n o pr ot oc ol de viati o ns or ot her circ u msta n ces t hat w o ul d e xcl u de t he m fr o m a nal ysis. 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
2 3  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
6. 0  
C H A N G E S F R O M T H E S T U D Y P R O T O C O L  
T here are  n o c ha n ges fr o m t he statistical a nal yses descri be d i n t he st u d y pr ot oc ol at t his ti me. 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
2 4  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
7. 0  
S T A TI S TI C A L M E T H O D S  
7. 1  
Re p orti n g C o n ve nti o ns a n d Defi niti o ns  
7. 1. 1  
St u d y Dr u g  
St u d y dr u g is defi ne d as A R R Y - 3 8 2 or pe m br oliz u ma b.  
7. 1. 2  
St u d y Tre at m e nt  
St u d y treat me nt is defi ne d as t he c o m bi nati o n of A R R Y - 3 8 2  +  pe m br oli z u ma b  or  si n gle-a ge nt 
A R R Y - 3 8 2.  
7. 1. 3  
B aseli ne  
Baseli ne is defi ne d as t he last a vaila ble a n d vali d assess me nt bef ore or at date of start of st u d y 
treat me nt. If a n assess me nt is pla n ne d t o be perf or me d pri or t o t he first d ose of st u d y dr u g i n t he 
pr ot oc ol a n d t he assess m e nt is perf or me d o n t he s a me da y as t he  first a d mi nistrati o n of st u d y dr u g 
a n d  t he  ti me  is  u n k n o w n,  it  will  be  ass u me d  t hat  it  was  perf or me d  pri or  t o  st u d y  dr u g  
a d mi nistrati o n  u nless t he pr ot oc ol s pecifies it ot her wise. U nsc h e d ule d assess me nts will be use d i n 
t he deter mi nati o n of b as eli ne. Data re p ort e d at t h e E n d of Treat me nt ( E O T) visit are n ot eli gi ble 
f or baseli ne selecti o n. T he E C G baseli ne will be t he a vera g e of tri plicate E C G meas ure me nts 
o btai ne d at pre - d ose o n Da y 1 of t he st u d y treat me nt.  
7. 1. 4  
L ast C o nt act D at e  
Last c o ntact date will be deri ve d f or patie nts n ot k n o w n t o ha ve die d o n or bef ore t he a n al ysis 
c ut off d ate. I m p ute d dates will n ot be c o nsi d ere d f or t he deter mi nati o n of l ast c o ntact date. O nl y 
dates ass ociate d wit h patie nt visits or t he act ual assess me nt of t he patie nt will be use d i n t he 
deri vati o n. Dat es ass ociate d wit h a tec h nical o p erati o n u nrelate d t o patie nt stat us (e. g. t he date a 
bl o o d sa m ple was pr ocesse d) will n ot be use d. Assess me nt dates after t he c ut off date will n ot be 
use d  t o deri ve t h e last c o ntact date. L ast c o ntact d ate will o nl y be deri ve d usi n g t he latest c o m plete 
date a m o n g  t he f oll o wi n g: 
•  St u d y dr u g start a n d e n d dates wit h n o n- missi n g d ose ( d oses of 0 are all o we d) 
•  R E CI S T assess me nt date wit h e val uati o n mar ke d as d o ne 
•  La b orat or y/ P K c ollecti o n date wit h sa m ple c ollecti o n mar ke d as d o n e 
•  Vital si g n , E C G , p h ysical e xa m, d er mat ol o gic e xa m  a n d o p ht hal mic e xa m assess me nt date 
wit h n o n- missi n g para meter val ue  
•  Perf or ma nce stat us date wit h n o n- missi n g perf or ma nce stat us 
•  Start/e n d  date of a d v erse e ve nts wit h n o n-missi n g ver bati m ter m  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
2 5  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•  Start/e n d date of a ntica n cer t h era pies a d mi nistere d after st u d y treat me nt; disc o nti n uati o n 
wit h n o n- missi n g me dicati o n/ pr oce d ure ter m 
•  Date  of  c o ntact  f or  m ost  rece nt  p ost -treat me nt  s ur vi val  assess me nt  wit h  t he  stat us  as   
“ Ali ve”  
•  Car diac i ma gi n g assess m e nt date  
 
 
7. 1. 5  
Tre at m e nt St art D ate  
Treat me nt start date is defi ne d as t he dat e patie nt recei ves t he first n o n -zer o d ose of st u d y dr u g.  
7. 1. 6  
St u d y D a y  
St u d y da y is defi ne d i n t he f oll o wi n g ma n ner:  
•  O n or after t he start date of st u d y treat me nt: ( date of assess me nt) – ( treat me nt start date) + 
1. St u d y da y 1 will t heref ore be t he first da y of st u d y treat me nt. 
•  Bef ore t he start date of st u d y treat me nt: ( date of assess me nt) – ( treat me nt start date).  
7. 1. 7  
Re p orti n g C o n ve nti o ns 
U nless s pecifie d ot her wise, d urati o ns of e ve nts (e. g., d urati o n of treat me nt) will be calc ulate d i n 
da ys as (st o p date – start date + 1).  
T he f oll o wi n g c o n versi o n fact ors will be use d t o c o n vert da ys i nt o wee ks, m o nt h s or years:  
1 wee k = 7 d a ys, 1 m o nt h = 3 0. 4 3 7 5 da ys, 1 year = 3 6 5. 2 5 da ys. 
De m o gra p hics a n d p h ysical meas ur e me nts : 
•  A ge ( years):  
­  ( date of gi ve n i nf or me d c o nse nt - date of birt h + 1) / 3 6 5. 2 5 
­  I n case of o nl y year a n d m o nt h gi ve n: A ge ( years): ( year/ m o nt h of gi ve n i nf or me d 
c o nse nt – year/ m o nt h of birt h) 
­  I n cas e o nl y year of birt h is gi ve n: A ge ( y ears): ( y ear of gi ve n i nf or m e d c o nse nt – 
year of birt h)  
­  T he i nte ger p art of t he calc ulate d a ge will be use d f or re p orti n g p ur p oses.  
All data c ollecte d i n t he d ata base will be use d f or t he statistical a nal ysis.  F or eac h a n al ysis a c ut off 
date will be  deter mi ne d. O nl y data wit h a n assess me nt date or e v e nt start date (e. g. vital si g n 
assess me nt date or start date of a n a d vers e e ve nt) bef ore  or o n t he c ut off d ate will be i ncl u de d i n 
t he a nal ysis.  
C
C
I


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Arr a y Bi o P h ar m a I nc.  
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C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
All e ve nts wit h a start date bef ore or o n t he c ut off date a n d a n e n d d ate aft er t he c ut off date will 
be c o nsi der e d as c o nti n ui n g at t he c ut off date. T he sa me r ule will be a p plie d t o e ve nts starti n g 
bef ore or o n t he c ut off date a n d n ot ha vi n g a d oc u me nte d e n d date.  
I n ge neral, missi n g val ues will be ha n dle d as f oll o ws u nless ot her wise s p ecifie d. F or c o nti n u o us 
varia bles at Baseli ne, missi n g val ues will be e x cl u de d fr o m cal c ulati o n of s u m mar y statistics, a n d 
t he n u m ber a n d per ce nt of patie nts wit h missi n g val ues will be dis pla ye d. F or cate g orical val u es 
at Baseli ne, t he n u m b er a n d perce nt of p atie nts wit h a missi n g val ue will be dis pla ye d. F or missi n g 
p ost- Baseli ne  val ues, t he met h o d f or re p orti n g missi n g val ues will de pe n d o n t he s u m mar y ta ble. 
Q ualitati ve /cate g ori cal d ata will be s u m marize d b y fre q u e nc y c o u nts a n d p erce nt a ges. Perce nt a ges 
will be calc ulate d usi n g t he n u m ber of p atie nt s or s u b gr o u p as t he de n o mi n at or. C o nti n u o us data  
will be s u m marize d usi n g a p pr o priat e d escri pti ve statistics (e. g. mea n, sta n d ar d de viati o n, me dia n, 
mi ni m u m, a n d ma xi m u m). 
F or  re p orti n g  c o n v e nti o ns,  mi ni m u m  a n d  ma xi m u m  val ues  will be  prese nte d  wit h t he  sa me  
deci mal precisi o n as c oll ecte d i n t he ra w d ata; mea n , me dia n , a n d q uartiles s h o ul d ge nerall y be 
prese nte d t o o ne m ore deci mal place t ha n t he ra w data ; sta n dar d d e viati o n s h o ul d be dis pla ye d t o 
t w o m ore deci mal places t ha n t he ra w data. Perce nta ges will be re p orte d t o o ne deci mal place. 
U nless ot her wise n ote d, f or all perce nta ges, t he n u m ber of patie nts i n t he a n al ysis set w h o ha ve a n 
o bser vati o n will be t he d e n o mi nat or. 
Al l a nal yses will be perf or me d a n d s u m marize d f or P hase 1 b a n d P hase 2 se parat el y. All P hase 
1 b ta bles will be prese nte d b y t he f oll o wi n g 4 gr o u ps, a n d t he listi n gs will be prese nt e d b y t he 
first 3 gr o u ps: 
2 0 0 m g A R R Y- 3 8 2 
+ 2 m g/ k g Pe m br o 
4 0 0 m g A R R Y- 3 8 2 
+ 2  m g/ k g Pe m br o 
 
3 0 0 m g A R R Y- 3 8 2 
+ 2 m g/ k g Pe m br o 
 
All P hase 1 b  
Patie nts  
 
 
All P hase 2 ta bles , listi n gs a n d fi g ures will be pres e nte d b y t he f oll o wi n g 3 gr o u ps: 
P D - 1/ P D- L 1 I n hi bit or Refract or y 
pr O V C A  
P D A  
 
Data listi n gs will be create d f or P hase 1 b a n d P hase 2 se parat el y, a n d will be s orte d b y patie nt 
i de ntifier, par a meter, a n d t he c orr es p o n di n g date of assess me nt.  T h e listi n g s o urce will be i n cl u de d 
i n t he f o oter of t he listi n gs.  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
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Versi o n 1. 0  
2 7  
C o nfi de ntial  
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7. 1. 8  
U nsc he d ule d Visits  
Ge ner all y, data c ollecte d at u nsc he d ule d visits will be i ncl u de d a n d a nal yze d f or b ot h safet y a n d 
n o n- safet y a n al yses i n t he sa me f as hi o n as t he data c ollecte d at sc he d ul e d visits e xce pt w here 
ot her wise  n ote d  i n  t he  secti o ns  t hat  f oll o w.  D escri pti ve  statistics  ( mea n,  sta n dar d  de viati o n,  
me dia n, mi ni m u m, ma xi m u m, q uartiles) b y n o mi nal visit or ti me p oi nt f or safet y e n d p oi nts s uc h 
as la b orat or y meas ure m e nts, E C Gs a n d vital si g ns will i ncl u de data fr o m sc he d ule d visits o nl y. 
7. 1. 9  
I m p ut ati o n R ules f or P arti al or Missi n g D ates 
7. 1. 9. 1  
Pri or  a n d C o nc o mit a nt M e dic ati o ns   
I nc o m plete c o n c o mita nt me dicati o n dates will be i m p ute d as f oll o ws:  
Me dic ati o n st art d at e  
•  If o nl y da y  of t he m o nt h is missi n g,  
− If m o nt h a n d year matc h t hat of t he treat me nt start date,  t he n i m p ute as (treat me nt start 
date + 1).  
− If m o nt h a n d year fall bef ore t he st u d y treat me nt start date, t he n i m p ute t he c o nc o mita nt 
me dicati o n start date  as t he 1 5t h da y of t he m o nt h. 
− If m o nt h a n d y ear f all after t he treat me nt start date, t he n i m p ute as t he 1st da y of t he 
m o nt h.  
•  If b ot h da y a n d m o nt h ar e missi n g,  
− If t he year matc h es t hat of t he treat me nt start date, t he n i m p ute as t he start date f or 
c o nc o mita nt me dicati o n  (treat me nt start date + 1). 
− If t he year is pri or t o t he treat me nt start date, t he n i m p ute start of t he c o nc o mita nt 
me dicati o n as J ul y 1 st.  
− If t he year is after t he treat me nt start date, t he n i m p ute as Ja n uar y 1st.  
•  I n all ot her cases t he i nc o m plete me dicati o n start d ate will n ot be i m p ute d . 
Me dic ati o n e n d  d ate  
•  If o nl y da y is missi n g,  
− If m o nt h a n d year matc h t hat of last c o ntact date, a n d t he me dicati o n wa s o n g oi n g, t he n 
i m p ute t he e n d date t o b e t he last da y of t he m o nt h. Ot her wise, i m p ute as last c o ntact 
date.  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
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Versi o n 1. 0  
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C o nfi de ntial  
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− If m o nt h a n d year are pri or t o  t he last c o ntact date, t he n i m p ute as t he last da y of t he 
m o nt h. 
•  If b ot h da y a n d m o nt h ar e missi n g,  
− If t he year matc hes t hat of last c o ntact date, a n d t he me dicati o n is o n g oi n g, t he n i m p ute 
as Dece m ber 3 1 st. Ot her wise, i m p ute as last c o ntact date.  
− If t he year is pri or t o or after last c o ntact date, t he n i m p ute as Dece m b er 3 1st.  
•  If t he me dicati o n e n d date is c o m pletel y missi n g a n d t he me dicati o n is o n g oi n g, i m p ute as 
last c o ntact date.  
•  I n all ot her cases t he i nc o m plete me dicati o n  e n d d ate will  n ot be i m p ute d.  
Ta ble 3  a n d Ta ble 4  pr o vi de e xa m ples f or differe nt sce nari os f or i m p uti n g c o nc o mita nt me dicati o n 
start a n d e n d dates, res p ecti vel y. T he i m p utati o n of t he start date of pri or a n d c o nc o mita nt n o n -
dr u g t hera p y will f oll o w t he sa me c o n v e nti o ns as f or c o nc o mita nt me dicati o n start date.  H o w e ver, 
i m p utati o n of n o n-dr u g t h era p y e n d dat e will be differe nt, as t he d ata c ollecte d o n n o n -dr u g t h era p y 
d oes n ot i ncl u de w het her t he t hera p y is o n g oi n g. T he i m p utati o n of n o n -dr u g t hera p y e n d date is 
as f oll o ws: c o m pletel y missi n g e n d dates will n ot be i m p ute d, e n d dates wit h o nl y da y missi n g 
will be i m p ute d t o t he last da y of t he m o nt h, a n d e n d dates wit h b ot h da y a n d m o nt h missi n g will 
be i m p ute d t o Dece m b er 3 1.  
Ta bl e 3: 
C o n c o mit a nt M e di c ati o n  St a rt D at e I m p ut ati o n E x a m pl e S c e n a ri os  
P arti al  
c o n me d st art d ate  
Tre at me nt  
st art d ate 
Te m p or al rel ati o ns hi p 
c o m p are d t o tre at me nt 
st art 
I m p ute d D ate 
1 2 M M M Y Y Y Y  
2 0 O C T 2 0 0 1  
U ncertai n  
< bla n k >  
D D M M M 2 0 0 0  
2 0 O C T 2 0 0 1  
Bef ore  
0 1J U L 2 0 0 0  
D D M M M 2 0 0 2  
2 0 O C T 2 0 0 1  
After  
0 1J A N 2 0 0 2  
D D M M M 2 0 0 1  
2 0 O C T 2 0 0 1  
U ncertai n  
2 1 O C T 2 0 0 1  
D D S E P 2 0 0 1  
2 0 O C T 2 0 0 1  
Bef ore  
1 5 S E P 2 0 0 1  
D D O C T 2 0 0 1  
2 0 O C T 2 0 0 1  
U ncertai n  
2 1 O C T 2 0 0 1  
D D N O V 2 0 0 1  
2 0 O C T 2 0 0 1  
After  
0 1 N O V 2 0 0 1  
 
 
 
 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
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Versi o n 1. 0  
2 9  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
Ta bl e 4: 
C o n c o mit a nt M e di c ati o n  E n d D at e I m p ut ati o n E x a m pl e S c e n a ri os  
P arti al  
c o n me d e n d d ate  
L ast c o nt act d ate  
O n g oi n g  
I m p ute d D ate 
Missi n g  
2 0 O C T 2 0 0 1  
Yes  
2 0 O C T 2 0 0 1  
D D M M M 2 0 0 0  
2 0 O C T 2 0 0 1  
N o  
3 1 D E C 2 0 0 0  
D D M M M 2 0 0 2  
2 0 O C T 2 0 0 1  
N o  
3 1 D E C 2 0 0 2  
D D M M M 2 0 0 1  
2 0 O C T 2 0 0 1  
N o  
2 0 O C T 2 0 0 1  
D D M M M 2 0 0 1  
2 0 O C T 2 0 0 1  
Yes  
3 1 D E C 2 0 0 1  
D D S E P 2 0 0 1  
2 0 O C T 2 0 0 1  
N o  
3 0 S E P 2 0 0 1  
D D O C T 2 0 0 1  
2 0 O C T 2 0 0 1  
N o  
2 0 O C T 2 0 0 1  
D D O C T 2 0 0 1  
2 0 O C T 2 0 0 1  
Yes  
3 1 O C T 2 0 0 1  
7. 1. 9. 2  
A d verse E ve nts  
T he i m p utati o n of t he st art dat e a n d e n d date of A Es will f oll o w t he s a me c o n ve nti o ns as f or 
c o nc o mita nt me dicati o n start date a n d e n d date.  
A Es  t hat are c o m pletel y missi n g a start date will be c o nsi dere d as treat me nt e mer ge nt if t he e n d 
date of t he A E is  eit her missi n g or occ urs after t he treat me nt start d ate.  I n t his case, i m p ute A E 
start date t o be treat me nt start date.  
7. 1. 9. 3  
De at h D ate  
Missi n g or partial deat h dates will be i m p ute d bas e d o n t he last c o ntact d ate : 
•  If t he date is c o m plet el y missi n g, it will be i m p ute d as t he da y after last c o ntact date .  
− N ote: A s p ecial cas e is t h e patie nt’s last c o nt act d ate is t he s a me as t he data c ut off d ate. 
I n t his case, his deat h d ate will be i m p ute d as t he da y after t he l ast c o ntact date. 
T heref ore, h e w o ul d be still ali ve as of t he data c ut off date.  
•  If t he da y or b ot h da y a n d m o nt h are missi n g, deat h date will be i m p ute d t o t he ma xi m u m 
of t he f ull ( n o n -i m p ute d)  [last c o ntact date (e x cl u di n g t he date of deat h) + 1] a n d t he 
f oll o wi n g: 
­  Missi n g da y: 1 5
t h da y of t he m o nt h a n d year of deat h 
­  Missi n g da y a n d m o nt h: J ul y 1
st of t he year of deat h 
7. 1. 9. 4  
E x p os ure D ate  
N o i m p utati o n will be d o ne f or start date of treat m e nt . Date of last d ose of st u d y dr u g if u n k n o w n 
or partiall y u n k n o w n will be i m p ute d as f oll o ws: 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
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Versi o n 1. 0  
3 0  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•  If t he last date of st u d y dr u g is c o m pletel y missi n g a n d t here is n o EO T e C R F pa ge a n d n o 
deat h date, t he patie nt s h o ul d be c o nsi dere d t o be o n -g oi n g a n d t he data c ut off date will be 
use d as t he last d osi n g date f or t he a n al ysis.  
•  If t he last date of st u d y dr u g is c o m pletel y or partiall y missi n g a n d t here is eit her a n E O T 
e C R F  pa ge or a deat h date a vaila ble ( wit hi n t he data c ut off date), t he n i m p ute d last d ose 
date will be as f oll o ws:  
o  = 3 1 D E C Y Y Y Y, if o nl y Ye ar  is a vaila ble a n d Year < Year of mi n ( E O T date, deat h 
date)  
o  = Last da y of t he m o nt h, if b ot h Ye ar a n d M o nt h  are a vaila bl e a n d Ye ar = Ye a r  
of mi n ( E O T date, d eat h date) a n d M o nt h < t he m o nt h of mi n ( E O T date, deat h  
date)  
o  = Last da y of t he m o nt h, if b ot h Ye ar a n d M o nt h  are a vaila bl e a n d Ye ar < Ye a r  
of mi n ( E O T date, d eat h date)  
o  = mi n ( E O T date, d eat h  d ate), f or all ot her cases  
T he i m p ute d date will be c o m pare d wit h start d ate of st u d y treat me nt:  
•  If t he i m p ute d date < start date of st u d y dr u g, t he n last date of st u d y dr u g is set t o start d ate 
of st u d y dr u g; 
•  Ot her wise, use t h e i m p ute d date.  
7. 1. 9. 5  
D ate of I niti al Di a g n osis of C a ncer  
I nc o m plete dates of i nitial dia g n osis of ca ncer will be i m p ute d as f oll o ws:  
•  If o nl y da y is missi n g, i m p ute as t he 1 5 t h da y of t he m o nt h.  
•  If b ot h da y a n d m o nt h are missi n g a n d t he year is pri or t o t he year of t he first st u d y 
treat me nt, i m p ute as J ul y 1st. 
•  If b ot h da y a n d m o nt h are missi n g a n d t he year is sa me as t he year of t he first st u d y 
treat me nt, i m p ute as Ja n u ar y 1 st.  
•  If t he date is c o m plet el y missi n g, n o i m p utati o n will be perf or me d. 
 
7. 1. 9. 6  
D ates of A nti c a ncer T h er a pies  
Pri or t her a pies :  
I nc o m plete start dates will be ha n dle d b y a p pl yi n g t he sa me i m p utati o n r ules as A E/c o n c o mita nt 
me dicati o ns start date e x ce pt:  
•  If o nl y da y is missi n g, a n d m o nt h a n d year matc h t hat of t he treat me nt start date, i m p ute as 
date of first d ose of st u d y dr u g - 1; 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
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Versi o n 1. 0  
3 1  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•  If b ot h da y a n d m o nt h are missi n g, a n d t he year matc hes t hat of t he treat me nt start date, 
t he n i m p ute as date of first d ose of st u d y dr u g – 1; 
•  C o m pletel y missi n g start date is i m p ute d as date of first d ose of st u d y dr u g – 1. 
I nc o m plete e n d dates a n d dates of pr o gressi o n  o n t he pri or a ntica ncer t h era pies will be ha n dle d 
usi n g t he f oll o wi n g r ule: 
•  If o nl y da y is missi n g , im p ute d date = mi n (first d ose of st u d y dr u g  -1, last da y of t he m o nt h);  
•  If b ot h m o nt h a n d da y ar e missi n g, i m p ute d date = mi n ( first d ose of st u d y dr u g  -1, 3 1 D E C) ; 
•  C o m pletel y missi n g e n d dates will n ot be i m p ute d.  
If t he e n d date or t he date of pr o gressi o n is n ot missi n g,  a n d t he i m p ute d start date is after t he e n d 
date or after t he date of pr o gressi o n, use t he mi n  (e n d date, date of pr o gressi o n) as t he i m p ute d 
start date. 
S u bse q ue nt  t her a pies:  
I nc o m plete s u bse q ue nt a ntica ncer t h era py start dates will be i m p ute d usi n g t he f oll o wi n g r ule: 
•  I m p ute d date = ma x (E O T d ate + 1, first da y of t h e m o nt h), if da y is missi n g; 
•  I m p ute d date = ma x (E O T d ate + 1, 0 1J A N), if da y a n d m o nt h are missi n g; 
•  Im p ute date = E O T date + 1 if t he date is c o m pletel y missi n g.  
E n d of Treat me nt Date is t he date of treat me nt disc o nti n uati o n as c ollecte d fr o m t he dis p ositi o n 
e C R F pa ge.  
T here will be n o i m p utati o n f or missi n g e n d dates. 
7. 2  
P atie nt Dis p ositi o n  
Patie nt dis p ositi o n a nal yses will use t he F A S u nless ot her wise state d.  
T he f oll o wi n g dis p ositi o n cate g ories will be s u m marize d:   
•  N u m ber ( %) of patie nts e nr olle d 
•  N u m ber ( %) of patie nts e nr olle d b ut n ot treate d 
•  N u m ber ( %) of patie nts w h o recei ve d at least o ne d ose of st u d y dr u g 
•  N u m ber ( %) of patie nts w h o are still o n treat me nt  
•  N u m ber ( %) of  patie nts w h o disc o nti n ue d t he treat me nt 
o  Pri mar y reas o ns f or treat me nt disc o nti n uati o n  
•  N u m ber ( %) of patie nts w h o disc o nti n ue d t he treat me nt b ut are still i n f oll o w - u p 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
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Versi o n 1. 0  
3 2  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•  N u m ber  ( %)  of  patie nts  w h o  were  n o  l o n ger  bei n g  f oll o we d  f or  st u d y  e val uati o n  
c o m pleti o n  
o  Pri mar y reas o ns f or st u d y e val uati o n c o m pleti o n 
I n cl usi o n a n d e xcl usi o n f or eac h of t he a n al ysis sets will als o be s u m marize d. 
Patie nt dis p ositi o n data will als o be liste d.  
Scree n f ail ure patie nts ar e t h ose w h o were scree n e d, b ut ne ver starte d t he st u d y treat me nt f or a n y 
reas o n. T he data c ollect e d o n t hese patie nts will n ot be i ncl u de d i n a n y a nal yses. A listi n g of 
reas o ns f or scr ee n f ail ure will be prese nte d.  
A se par ate listi n g will descri be eac h patie nt’s i n cl usi o n or e xcl usi o n stat us f or eac h of t he a n al ysis 
sets defi ne d i n Secti o n  5. 0 . 
7. 3  
Pr ot oc ol D e vi ati o ns 
Pr ot oc ol de viati o ns will be deter mi ne d a n d d o c u me nte d pri or t o data base l oc k  as o utli ne d i n t he 
S pecific ati o ns of Pr ot oc ol Devi ati o ns . T h e n u m ber a n d p erce nta ge of patie nts i n t he F A S wit h a n y 
pr ot oc ol  de viati o ns  will  be  ta b ulate d  b y  de viati o n  cate g or y,  st u d y  part  a n d  c o h ort.  Pr ot oc ol 
de viati o ns will be prese nte d i n a data listi n g.  
7. 4  
P atie nt C h ar act eristics  
Patie nt c haracteristic a n al yses will be perf or me d usi n g t he F A S.  
7. 4. 1  
De m o gr a p hics a n d Pretre at me nt C h ar acteristi cs  
De m o gra p hic a n d ot her pretreat me nt c haracteristics  i ncl u di n g a ge, ge n der, race, et h nicit y, hei g ht, 
wei g ht, a n d E C O G perf or ma nce s tat us, will be s u m marize d. 
A de m o gra p hics l isti n g b y patie nt will be create d.  
7. 4. 2  
Me dic al a n d Dise ase Hist or y  
S u m mar y of disease hist or y will be create d i ncl u di n g  date of i nitial dia g n osis, sta ge at dia g n osis 
a n d sta ge at st u d y e ntr y. 
Me dical a n d d isease hist or y will also be liste d f or eac h p atie nt . 
7. 4. 3  
S u bst a nce Use  
Data o n t o bacc o use a n d alc o h ol use as c ollecte d o n t he S u bsta nce Use e C R F pa ge will be i ncl u de d 
i n a listi n g. 


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7. 4. 5  
Pri or A ntic a ncer  T her a p y  
Pri or a ntica ncer t her ap y will be s u m marize d f or t hr ee disti nct s u bt y pes   - s yste mic treat me nt, 
ra di ot hera p y a n d s ur g er y. Nu m ber ( %) of patie nts w h o recei ve d, s e paratel y, a n y pri or s yste mic 
treat me nt, ra di ot hera p y, or s ur ger y will be s u m marize d.  
F or p ri or s yste mic tr eat me nt, t he f oll o wi n g dat a as c ollecte d  o n t he “ Pri or S yste mic Ca ncer 
Treat me nts” eC R F pa ge will be s u m m arize d:  
•  N u m ber of patie nts wit h at least o n e pri or s yste mi c treat me nt  
•  T otal n u m ber of r e gi me ns (t here ca n be m ore t ha n o ne me dicati o n per re gi me n) 
•  T y pe of pri or tr eat me nts  
•  I n dicati o n at t he last pri or t hera p y  ( b ase d o n t he e n d date) 
•  B est res p o nse at t he last pri or  t hera p y ( defi ne d as t he best res p o nse d uri n g t he last treat me nt 
re gi me n rec or de d) 
Pri or s yste mic treat me nts will als o be s u m marize d b y A nat o mical T hera p e utic C he mical ( A T C) 
class a n d P T . 
F or pri or a ntica n cer ra di ot hera p y, t he f oll o wi n g i nf or mati o n a b o ut t he l ast r a di ot her a py ( base d o n 
e n d date) will be s u m marize d : l ocati o n, i nte nt of t he ra diati o n a n d b est res p o nse .  
F or pri or a ntica ncer s ur g er y, t y pe of pr oce d ure a n d res ult of pr oce d ure will be s u m marize d.  
All pri or a ntica ncer t her a pies will be liste d se paratel y f or s yste mic treat me nt, ra di ot hera p y, a n d 
s ur ger y. 
I n c o m plete dates will be ha n dle d as des cri be d i n Secti o n 7. 1. 9. 6  . 
C CI


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Ot her Pri or Me dic ati o ns  a n d Pr oce d ures  
Pri or  me dicati o ns  ( defi ne d  as  a n y  me dicati o ns,  e xcl u di n g  st u d y  dr u g  a n d  pri or  a ntica n cer  
treat me nts)  a n d  si g nifi ca nt  n o n-dr u g  t hera pies  (i ncl u di n g  p h ysical  t hera p y,  her b al/ nat ural  
me dicati o ns , a n d bl o o d tr a nsf usi o ns) rec or de d i n t he “ Pri or a n d C o n c o mita nt Me dicati o ns ” e C R F  
will be s u m marize d. T h ese me dicati o ns a n d t h era pies will be c o d e d usi n g t he W orl d Healt h 
Or ga nizati o n  Dr u g  Ref ere nce  Listi n g  ( W H O  D R L)  dicti o nar y  t hat  e m pl o ys  t he  W H O  A T C  
classificati o n s yste m.  
T he n u m ber a n d p erce nt a ge of patie nts will be s u m marize d f or m e dicati o ns/ n o n-dr u g t hera pies 
t hat were st o p pe d pri or t o start of st u d y dr u g.   
A listi n g will be pr o d uce d f or me dicati o ns/ n o n -dr u g t hera pies t hat were st o p pe d pri or t o start of 
st u d y dr u g. 
I n c om plete dates will be ha n dle d as des cri be d i n  Secti o n 7. 1. 9 . 
7. 5  
Effic ac y A n al ysis 
Efficac y a nal ys es will be perf or me d usi n g t he F A S .  
7. 5. 1  
O bjecti ve R es p o nse R at e 
O R R is  defi ne d as t he pr o p orti o n of patie nts w h o ha ve ac hie ve d a best o verall res p o nse ( B O R) of 
c o m plete  r es p o nse  ( C R) or partial  res p o ns e  ( P R) as  det er mi ne d  b y  I n vesti gat or  re vi e w  of  
ra di o gra p hic disease ass ess me nts per R E CI S T v 1. 1 . B ot h c o nfir me d a n d u nc o nfir me d O R R will 
be s u m marize d, b ut t he pri mar y a nal ysis will be b ase d o n c o nfir m e d res p o nses. 
T he B O R is d efi ne d as t he best res p o nse  rec or d e d fr o m t h e st u d y start dat e u ntil pr o gressi o n a n d 
will be deter mi ne d pr o gr a m maticall y base d o n t he I n vesti gat or’s assess me nt of t u m or res p o ns e at 
eac h ti me p oi nt  per R E CI S T v 1. 1. O nl y t u m or assess me nts perf or me d bef ore t h e start of a n y 
s u bse q ue nt a ntica ncer t h era pies a n d n ot later t ha n 3 0 da ys after last d ose of st u d y dr u g will be 
c o nsi dere d i n t he assess m e nt of best o verall  res p o nse. Cli nical deteri orati o n or cli nical pr o gressi o n 
n ote d o n t he E n d of Treat me nt Dis p ositi o n  e C R F will n ot be c o nsi d ere d as d oc u me nte d disease 
pr o gressi o n f or t he p ur p oses of t he O R R  calc ulati o n. 
T he c o nfir me d B O R f or eac h patie nt is deter mi ne d fr o m t he se q ue n ce of o verall ti me p oi nt (lesi on) 
res p o nses acc or di n g t o t h e f oll o wi n g r ules bel o w: 
C R = at least t w o deter mi nati o ns of C R at least 4 wee ks a p art bef ore pr o gressi o n, w here 
c o nfir mati o n  re q uire d,  or  o ne  deter mi nati o n  of  C R  pri or  t o  pr o gressi o n,  w here  
c o nfir mati o n n ot re q uir e d. 


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P R = at least t w o deter mi nati o ns of P R or better at least 4 wee ks a part bef ore pr o gressi o n 
(a n d n ot q ualif yi n g f or a C R), w here c o nfir mati o n re q uire d, or o ne deter mi nati o n of P R 
pri or t o pr o gressi o n, w here c o nfir m ati o n n ot re q uire d. 
S D = a n assess me nt of S D or b etter > 6 wee ks after start of treat me nt (a n d n ot q ualif yi n g 
f or P D, P R or C R). 
P D = pr o gressi o n ≤ 9 wee ks after start of treat me nt  (a n d n ot q ualif yi n g f or C R, P R, or S D). 
N E ( N ot E val u a ble) = all ot her cases (i.e. n ot q ualif yi n g f or c o nfir me d C R or P R a n d 
wit h o ut S D after m ore t h a n 6 wee ks or earl y pr o gressi o n wit hi n t he first 9 wee ks).  
Patie nts wit h c o nfir me d best o verall res p o nse ‘N ot E val ua ble’ will be s u m marize d b y reas o n f or 
ha vi n g u n k n o w n stat us. T he f oll o wi n g reas o ns will be use d: 
•  N o baseli ne ass ess me nt  
•  N o a de q uat e p ost-baseli n e assess me nt  
•  All p ost- baseli ne assess me nts ha ve o verall res p o nse of “ N E ”  
•  Ne w a ntica ncer t her a p y starte d bef ore first p ost-b aseli ne assess me nt  
•  S D occ urr e d ≤ 6 wee ks after t he start of treat me nt  
•  Pr o gressi o n  > 9 w ee ks  after  t he  start  of  treat me nt  (i.e.  t u m or  ass ess me nt  of  P D  was 
> 9 wee ks after start of tr eat me nt a n d t here was n o t u m or assess me nt i n bet wee n)  
S pecial (a n d rar e) cases w here B O R  is ‘N ot e val ua ble’ d ue t o b ot h S D occ urri n g ≤ 6 wee ks after 
start of treat me nt a n d pr o gressi o n > 9 w ee ks after t he start of treat me nt will be classifie d as “ S D 
occ urr e d ≤ 6 wee ks after t he start of treat me nt ”.  
T he O R R will be calc ul ate d  wit h a n e xact t w o -si d e d 95 % CI.  T he 9 5 %  CI will be deri ve d usi n g 
t he Cl o p per- Pears o n 4 e x act bi n o mial CI met h o d. I n a d diti o n, t he n u m ber a n d perce nt a ge of p atie nts 
i n eac h B O R  cate g or y (i.e., C R, P R, sta ble disease (S D ), pr o gressi ve disease ( P D ),  a n d N ot 
E val ua ble ) will be s u m m arize d. 
A fi g ure f or d ur ati o n of e x p os ure a n d be st o v erall res p o nse (c o nfir me d) will be create d. 
A waterfall pl ot will be create d t o s h o w t he best perce nt a ge c ha n g e fr o m t he baseli ne i n t he s u m 
of l o n gest dia meters. Patie nts wit h baseli ne a n d at least o ne p ost -b aseli ne t u m or assess me nt will 
be i ncl u de d i n t he wat erf all pl ot. 
I n di vi d ual lesi o n meas ur e me nts a n d o verall res p o nse assess me nts per R E CI S T v 1. 1 will be liste d 
b y patie nt a n d assess me nt date.  


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7. 5. 2  
D ur ati o n of Res p o nse  
D O R  is defi ne d as t he ti me fr o m t he date of t he first d oc u me nte d res p o nse ( C R or P R) t o t he 
earliest date of diseas e pr o gressi o n, as deter mi ne d b y I n vesti gat or re vie w of ra di o gra p hic diseas e 
assess me nts per R E CI S T v 1. 1, or deat h d ue t o a n y ca use . If a patie nt wit h a C R or P R has neit her 
pr o gresse d n or die d at t h e ti me of t he a n al ysis c ut off or at t he start of a n y n e w a ntica n cer t hera p y, 
t he patie nt will be ce ns or e d at t he d ate of last a d e q uate t u m or assess m e nt. D O R will be calc ul ate d 
f or patie nts w h o ha v e ac hie ve d a c o nfir me d o verall res p o nse (i.e., C R or P R). 
A n esti mate of t he  D O R s ur vi val f u ncti o n will be c o nstr ucte d usi n g t he K a pla n -Meier ( pr o d u ct -
li mit) met h o d (Ka pla n & Meier, 1 9 5 8 ) as i m ple m e nte d i n P R O C LI F E T E S T. T he 2 5 %, me dia n, 
a n d 7 5 % D O R (i n m o nt hs) will be s u m marize d al o n g wit h 9 5 % CIs  as calc ulate d fr o m t he P R O C 
LI F E T E S T o ut p ut ( usi n g met h o d of [ Br o o k me yer & Cr o wle y, 1 9 8 2 ]).   
Fre q ue nc y c o u nts a n d perce nta g es of patie nts wit h eac h e ve nt t y pe ( P D or deat h) a n d ce ns ori n g 
reas o ns will be s u m marize d. Ce ns ori n g reas o ns are as f oll o ws:  
•  O n g oi n g i n t he st u d y wit h o ut a n e ve nt  
•  N o baseli ne ass ess me nt  
•  N o p ost- baseli ne ass ess me nt  
•  Ne w a ntica ncer t her a p y was gi ve n  
•  Pr o gressi o n after 2 or m ore misse d assess me nts  
•  Deat h aft er 2 or m or e misse d asse ss me nts 
•  A de q uate assess me nt n o l o n ger a vaila ble  
•  Wit h dra wal of c o nse nt 
•  L ost t o f oll o w- u p 
A Ka pla n - Meier pl ot of t he s ur vi val f u ncti o n will be pr o vi de d as w ell. 
D urati o n of res p o ns e will be liste d. 
7. 5. 3  
Pr o gressi o n -f ree S ur vi v al 
P F S  is defi ne d as t he ti me fr o m t he d ate of first d ose of st u d y dr u g  t o t he earliest date of diseas e 
pr o gressi o n,  as  deter mi ne d  b y  I n vesti gat or  re vie w  of  ra di o gra p hi c  disease  assess me nts  per  
R E CI S T v 1. 1, or deat h d ue t o a n y ca us e.  
If a patie nt has n ot ha d a P F S e ve nt at t he ti me of t he a nal ysis c ut off or at t he start of a n y ne w 
a ntica ncer t hera p y, P F S will be  ce ns ore d at t he date of last a de q uate t u m or assess me nt.  If a P F S 
e ve nt is o bser ve d after m ore t ha n o ne missi n g or i na de q uate t u m or ass ess me nt, P F S will be 


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ce ns ore d at t he last a de q uate t u m or assess me nt. If a P F S e ve nt is o bser ve d after a si n gle missi n g 
or n o n -a de q uat e t u m or assess me nt, t he act ual date of e ve nt w ill be use d. Patie nts w h o d o n ot ha ve 
baseli ne or p ost- bas eli ne t u m or assess me nts will be ce ns ore d at t he st u d y st art date . 
T he last a de q uate t u m or assess me nt is defi ne d as a t u m or assess me nt  res ult t hat is n ot “ N E”, “ N D”, 
“ N A” or missi n g . 
T he s ur vi val distri b uti o n f u ncti o n f or P F S will be esti mate d usi n g t he Ka pla n -Meier  (K M ) met h o d 
as desc ri be d f or D O R i n Secti o n 7. 5. 2 . The P F S  rate at 2, 4 a n d 6  m o nt hs will be esti mate d wit h 
c orres p o n di n g t w o-si d e d 9 5 % CIs. 
Fre q ue nc y c o u nts a n d perce nta g es of patie nts wit h eac h e ve nt t y pe ( P D or deat h) a n d ce ns ori n g  
reas o ns will be s u m marize d as descri be d i n Secti o n 7. 5. 2 .  
I n a d diti o n, ti me t o pr o gressi o n/ce ns ori n g, e ve nt a n d ce ns ori n g reas o ns will be liste d.   
7. 5. 4  
O ver all S ur vi v al 
O S  is defi ne d as t he ti me fr o m t he date of first d ose of st u d y dr u g t o t he date  of deat h d u e t o a n y 
ca use. If a deat h has n ot bee n o bser v e d b y t he dat e of t he a nal ysis c ut off, O S will be ce ns ore d at 
t he date of last c o nt act.  
T he  s ur vi val distri b uti o n f u ncti o n f or O S will b e esti mate d usi n g t he K M  m et h o d as d escri b e d f or 
D O R i n S ecti o n 7. 5.2 . Th e O S  rat e at 2, 4, 6, 8 a n d 1 0 m o nt hs will be esti mate d wit h c orres p o n di n g 
t w o-si de d 9 5 % CIs. 
Fre q ue nc y c o u nts a n d perce nta g es of patie nts wit h a n e ve nt ( deat h) a n d ce ns ori n g reas o ns will be 
s u m marize d. Ce ns ori n g r eas o ns ar e as f oll o ws:  
•  O n g oi n g a n d n o deat h 
•  L ost t o f oll o w- u p 
 
7. 5. 5  
I m m u ne-rel ate d Res p o nse R ate  
I m m u ne-relat e d R R (ir R R) is defi ne d as t he pr o p orti o n of patie nts w h o ac hie ve i m m u ne-relate d 
b est o verall   res p o nse (ir B O R) of i m m u ne-rel ate d C R (irC R) or i m m u ne-relate d P R (ir P R), as 
deter mi ne d b y t he I n vesti gat or per  ir R C, w here ir B O R is t he best res p o nse usi n g ir R C rec or de d 
fr o m t he start of st u d y treat me nt u ntil t he e n d of treat me nt.   
T he c o nfir me d ir B O R  f or eac h p atie nt is det er mi ne d fr o m t he se q ue n ce of o verall ti me p oi nt 
(lesi o n) res p o ns es per ir R C as s u m marize d i n A p pe n di x 6 i n t he st u d y pr ot oc ol. T he deri vati o n of 
B O R wit h c o nfir mati o n re q uire me nt as d efi ne d i n Secti o n 7. 5. 1  will be use d t o deter mi ne t he 


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ir B O R. I n a d diti o n, I m m u ne-rel ate d P D  (ir P D) n ee ds t o be c o nfir m e d b y a re peat, c o nsec uti ve 
assess me nt n o less t ha n 4 wee ks fr o m t he first d oc u me nte d date. 
T he ir RR will be cal c ulat e d al o n g wit h t he t w o -si de d e x act Cl o p per-Pears o n  9 5 % CIs. I n a d diti o n, 
t he n u m ber a n d perce nt a ge of patie nts i n eac h B O R  cate g or y, i.e., irC R, irP R, i m m u ne-relate d S D 
(irS D ), ir P D, a n d i m m u ne-rel ate d U ne v al ua ble (ir U ne val ua ble) will be s u m marize d. 
7. 5. 6  
I m m u ne-rel ate d Pr o gressi o n -free S ur vi v al 
I m m u ne-relat e d P F S  (ir P F S) is defi ne d as t he ti m e fr o m t he st art of treat m e nt t o t he ti me of first 
d oc u me nte d pr o gr essi o n per ir R C, as deter mi ne d b y t he I n vesti gat or or d eat h d ue t o a n y ca use.  
F or t he a nal ysis of ir P F S, t he Ka pla n -M eier met h o d as defi ne d i n  Secti o n 7. 5. 3  will be perf or m e d, 
a n d t he sa me ce ns ori n g r ules as descri b e d i n Secti o n 7. 5. 3  will be a p plie d.  
 
7. 6  
S afet y A n al ysis 
All safet y a nal yses will be perf or me d usi n g t he a p pr o priate data f or all patie nts i n t he S S  u nless 
ot her wise state d.  
7. 6. 1  
E xte nt of St u d y Dr u g E x p os ure  
D urati o n of e x p os ur e is defi ne d as f oll o ws a n d will be s u m marize d wit h  d escri pti ve statistics ( n, 
mea n, me dia n, mi ni m u m, ma xi m u m) .  
A R R Y - 3 8 2: 
D ur ati o n of e x p os ure  ( da ys) = date of last ( n o n -zer o) d ose of A R R Y - 3 8 2 – date of first 
d ose of A R R Y - 3 8 2 + 1  
Pe m br oliz u ma b : 
D ur ati o n of e x p os ure  (wee ks ) = ( date of last ( n o n-zer o) d ose of p e m br oliz u ma b  - date of 
first d ose of pe m br oliz u ma b  + 2 1)/ 7 
C u m ulati ve d ose is defi ne d as: 
A R R Y - 3 8 2: 
•  Pl a n ne d c u m ul ati ve d ose  ( m g) = s u m of all pr ot oc ol s pecifie d d oses acr oss eac h pla n ne d 
da y of d osi n g 
•  Act u al c u m ul ati ve d ose  ( m g) = s u m of all act ual d oses ta ke n d uri n g t he d osi n g peri o d 
Pe m br oliz u ma b : 


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•  Pl a n ne d c u m ul ati ve d ose  ( m g/ k g) = s u m of all pr ot oc ol s pecifie d d oses acr oss t he d osi n g 
peri o d 
•  Act u al c u m ul ati ve d ose  ( m g/ k g) = s u m of all act ual d oses ta ke n d uri n g t he d osi n g peri o d 
T he d ose of pe m br oliz u ma b  ta ke n at eac h visit is calc ulate d as t otal ( pla n ne d a n d act u al) d ose 
a d mi nistere d  ( m g) at eac h visit / wei g ht ( k g) at t hat visit.  
F or patie nts w h o di d n ot ta ke a n y dr u g t he act ual c u m ulati ve d ose is b y defi niti o n e q ual t o zer o.  
D ose i nte nsit y a n d relati ve d ose i nte nsit y are d efi ne d as f oll o ws:  
A R R Y - 3 8 2: 
•  Pl a n ne d d ose i nte nsit y  ( m g/da y ) = pla n ne d c u m ulati ve d ose ( m g) / [ d urati o n of e x p os ure 
( da ys)] 
•  Act u al d ose i nte nsit y  ( m g/da y ) = act ual c u m ulati ve d ose ( m g) / [d urati o n of e x p os ure 
( da ys)] 
•  Rel ati ve d ose i nt e nsit y = 1 0 0 *[act ual d ose i nte nsit y ( m g/ da y ) / pla n ne d d ose i nte nsit y 
( m g/ da y)] 
Pe m br oliz u ma b : 
•  Pl a n ne d d ose i nte nsit y  ( m g/k g/ c ycle) = pla n ne d c u m ulati ve d ose ( m g/ k g) / [d urati o n of 
e x p os ure ( wee ks)/ 3] 
•  Act u al d ose i nte nsit y   ( m g/ k g/c ycle) = act ual c u m ulati ve d ose ( m g / k g) / [ d urati o n of 
e x p os ure ( wee ks)/ 3] 
•  Rel ati ve  d ose  i nte nsit y  =  1 0 0 *[act u al  d ose  i nte nsit y  ( m g/ k g/c ycle )  /  pla n ne d  d ose  
i nte nsit y ( m g/ k g/c ycle)] 
A s u m mar y of e x p os ure, i ncl u di n g d urati o n, c u m ulati ve d ose, act ual d ose i nte nsit y, a n d rel ati ve 
d ose i nte nsit y (i ncl u di n g cate g ories < 5 0 %, 5 0 % -< 7 5 %, 7 5 % -< 9 0 %, 9 0 % -< 1 1 0 %, a n d ≥1 1 0 %, if 
a p plica ble), will be pres e nte d f or eac h st u d y dr u g.  D urati o n of e x p os ure, c u m ulati ve d ose, act ual 
d ose i nte nsit y, a n d relati ve d ose i nte nsit y will als o be liste d  f or eac h patie nt. 
7. 6. 1. 1  
D ose M o dific ati o ns 
D ose re d ucti o n:  
D ose r e d ucti o ns ar e p er mitte d f or  A R R Y - 3 8 2.  A d ose re d ucti o n is d efi n e d as a decrease i n d ose 
fr o m t he pr ot oc ol pla n n e d d ose a n d a decrease fr o m t he pre vi o us n o n-zer o d ose, e v e n if t his 
decrease h as be e n dir ectl y prece d e d b y a n i nterr u pti o n.  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
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Versi o n 1. 0  
4 0  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
If a patie nt’s d ose decreases fr o m a hi g her t ha n pr ot oc ol pla n ne d d ose t o t h e pla n ne d d ose, t his is 
n ot c o u nte d as a r e d ucti o n ; h o we ver, if t he d ose is re d uce d  directl y fr o m a hi g her t h a n pla n ne d 
d ose t o a l o wer t ha n pr ot oc ol pla n ne d d ose or t he pla n ne d d ose o n a less fre q ue nt re gi me n, t his is 
c o u nte d as a re d ucti o n. 
If t he d ose o n t he first d osi n g rec or d is l o wer t ha n pr ot oc ol pla n ne d d ose t his is als o c o u nte d as a 
re d ucti o n. 
D ose re d u cti o n will be s u m marize d bas e d o n t he d ose m o dificati o n dat a c ollecte d o n t h e e C R F 
pa ge.  
D ose i nterr u pti o n:  
A d ose i nterr u pti o n will be i n dicate d i n t he e C R F b y a d osi n g rec or d wit h a t otal dail y d ose of 
0 m g f or o ne or m or e da ys.  
D ose i nterr u pti o n will be s u m marize d base d o n t h e d ose m o dificati o n d ata c ollecte d o n t he e C R F 
pa ge. H o w e ver, i n or d er n ot t o o ver c o u nt i nterr u pti o ns, d osi n g rec or ds wit h 0 m g e ntere d as last 
d osi n g rec or d will n ot be c o u nte d as i nterr u pti o ns. T h ose re prese nt t he reas o n f or per ma n e nt 
disc o nti n uati o n a n d will t heref ore be pr ese nte d i n t he reas o n f or treat me nt disc o nti n uati o n a nal ysis.  
Fre q u e nc y  c o u nts  a n d  perce nt a ges  of  patie nts  w h o  ha ve  d ose  re d ucti o ns  or  a n y  st u d y  dr u g  
i nterr u pti o ns, a n d t he c orres p o n di n g reas o ns, will be pr o vi de d. T he n u m ber of d ose i nterr u pti o ns 
per patie nt, a n d t he d urati o n of d ose i nterr u pti o ns ( da ys) will als o be  s u m marize d f or eac h st u d y 
dr u g. 
7. 6. 2  
C o nc o mit a nt Me dic ati o ns 
C o nc o mita nt  me dicati o ns  are defi ne d  as  a n y  me dicati o ns  (e xcl u di n g  st u d y  dr u g  a n d  pri or  
a ntica ncer treat me nts)  a n d  si g nifica nt  n o n-dr u g  t hera pies  (i ncl u di n g  p h ysical  t hera p y,  
her bal/ nat ur al me dicati o n s a n d bl o o d tra nsf usi o ns) a d mi nistere d i n t he st u d y a n d rec or d e d i n t he 
Pri or a n d C o nc o mita nt Me dicati o ns e C R F.  
C o nc o mita nt me dicati o ns will be c o d e d usi n g t h e latest v ersi o n of t he W H O  Dr u g Refere nce 
Listi n g  dicti o nar y a vaila ble at t he ti me of re p orti n g  a n d will b e s u m marize d b y A T C (l e vel 2) a n d 
P T  (le vel 4).  T hese s u m maries will i ncl u de:  
1.  me dicati o ns starti n g o n or after t he start of st u d y treat me nt b ut n o later t ha n 3 0 da ys aft er 
last d ose of st u d y treat me nt, a n d 
2.  me dicati o ns starti n g pri or t o t he start  of st u d y treat me nt a n d c o nti n ui n g after t he st art of 
st u d y treat me nt. 
All c o nc o mita nt me dicati o ns will be liste d.  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
4 1  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
I nc o m plete dates will be ha n dle d as des cri be d i n Secti o n 7. 1. 9. 1 . 
7. 6. 3  
S u bse q ue nt A ntic a ncer  T her a pies  
S u bse q ue nt a ntica ncer t h era pies i ncl u d e a ntica n cer s yste mic t hera p y, a ntica ncer ra diati o n or 
a ntica ncer s ur ger y. 
S u bse q ue nt a ntica ncer s yste mic t hera p y  will be s u m marize d b y A T C class  (le vel 2 ) a n d P T . 
S u bse q ue nt a ntica ncer s yste mic t hera p y, ra diot hera p y, a n d s ur ger y will be liste d.  
I nc o m plete dates will be ha n dle d as des cri be d i n Secti o n 7. 1. 9. 6 . 
7. 6. 4  
A d verse E ve nts  
A Es  a n d seri o us a d verse e ve nts ( S A Es) will be c o de d b y P T a n d S O C usi n g t he latest a vaila ble 
Me d D R A  versi o n.  
T he se v erit y of  a n A E will be assesse d b y t he i n v esti gat or usi n g t he N CI  C T C A E , Versi o n 4. 0 3. 
F or patie nts wit h m ore t ha n 1 A E wit hi n a S O C or P T, o nl y t he hi g hest gra de will be i ncl u de d i n 
b y- se verit y s u m maries.  
T he i n vesti gat or will als o assess w h et her t h e A E is s us pecte d t o b e relate d t o st u d y dr u g (i.e., a 
treat me nt-r elate d A E). F or patie nts wit h m ore t ha n 1 A E wit hi n a S O C or P T, t he hi g hest le vel of 
relati o ns hi p (relat e d is hi g her t ha n n ot rel ate d) will be i ncl u de d i n t he b y-relati o ns hi p s u m maries.  
F or s u m maries b y S O C a n d P T, eac h patie nt will be c o u nte d at m ost o nce per S O C a n d at m ost 
o nce per P T. F or s u m maries b y P T, eac h patie nt will be c o u n te d at m ost o nce per P T. 
Treat me nt -e mer ge nt A Es ( T E A Es) will be defi ne d as : 
•  A n y ne w e ve nt t hat starts after a d mi nistrati o n of st u d y dr u g  a n d ≤ 3 0 da ys after treat me nt 
disc o nti n uati o n. 
•  A n y e ve nt t hat was o n g oi n g w he n treat me nt wit h st u d y dr u g starte d a n d t he se verit y/ gra d e 
after  treat me nt  was  hi g her  t ha n  t he  Baseli ne  val ue  (fl uct uati o ns  bel o w  t he  Baseli ne  
se verit y/ gra de ar e n ot c o nsi dere d as treat me nt e m er ge nt). 
•  A n y ne w e ve nt t hat starts > 3 0 d a ys after treat me nt disc o nti n uati o n a n d is assesse d b y t he 
I n v esti gat or as r elate d t o st u d y treat me nt. 
E ver y eff ort s h o ul d be ma de t o o btai n start d ates f or a d v erse e ve nts ( A Es).  If a n A E is missi n g 
t he start date, a n d t he ti mi n g of t he start date relati ve t o treat me nt start is n ot k n o w n, it s h o ul d be 
c o nsi dere d as t reat me nt e mer ge nt f or re p orti n g a n d a nal ysis p ur p oses. 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
4 2  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
U nless ot her wise state d, o nl y T E A Es will be prese nte d i n s u m mar y ta bles. H o we ver, all A Es will 
be prese nt e d i n listi n gs.  
O verall s u m mar y of s afet y ta ble will i ncl u de n u m bers a n d perce nt a ges of t h e f oll o wi n g:   
•  Patie nts w h o die d o n st u d y or wit hi n 3 0 da ys of last treat me nt 
•  Patie nts wit h at least 1 T E A E re gar dless of ca usalit y  
•  Patie nts wit h at least 1 treat me nt  relat e d T E A E 
•  Patie nts wit h treat me nt  relate d T E A Es b y w orst se verit y 
•  Patie nts wit h at least 1 treat me nt-e mer ge nt S A E ( T E S A E)  
•  Patie nts wit h at least 1  treat me nt-relate d T E S A E 
•  Patie nts w h o disc o nti n ue d st u d y dr u g d ue t o a T E A E re gar dless of ca usalit y 
•  Patie nts w h o disc o nti n ue d st u d y dr u g d ue t o a treat me nt- relate d T E A E 
•  Patie nts wit h a d ose re d u cti o n d ue t o a T E A E 
•  Patie nts wit h a d ose i nterr u pti o n d ue t o a T E A E 
All T E A E s u m maries will be dis pla ye d (fre q ue n c y c o u nts a n d perce nta g es) al p ha beticall y b y  
s yste m or ga n class ( S O C) a n d pref err e d ter m ( P T) b y desce n di n g fre q u e nc y wit hi n S O C , if n ot 
ot her wise n ote d.  I n di vi d ual s u m mar y ta bles s h o wi n g t he i nci de nce of patie nts wit h t he f oll o wi n g 
s u bsets of T E A Es will be ge nerat e d: 
•  T E A Es , re gar dless of ca usalit y, b y S O C, P T a n d ma xi m u m se verit y 
•  T E A Es , re gar dless of ca usalit y, b y S O C a n d  P T  
•  T E A Es, re gar dless of ca usalit y, b y P T 
•  Treat me nt -relate d T E A Es wit h sus pecte d relati o ns hi p t o A R R Y - 3 8 2 b y S O C, P T a n d 
ma xi m u m se verit y  
•  Treat me nt -relate d T E A Es wit h sus pecte d relati o ns hi p t o pe m br oliz u ma b b y S O C, P T a n d 
ma xi m u m se verit y  
•  Treat me nt -relate d T E A Es wit h s us pecte d relati o ns hi p t o A R R Y - 3 8 2 b y P T 
•  Treat me nt -relate d T E A Es wit h sus pecte d relati o ns hi p t o pe m br oliz u ma b b y P T  
•  T E S A Es, re gar dl ess of ca usalit y, b y S O C, P T a n d ma xi m u m se verit y 
•  T E S A Es, re gar dl ess of ca usalit y, b y S O C a n d P T 
•  T E S A Es, re gar dl ess of ca usalit y, b y P T 
•  T E S A Es  wit h sus pecte d relati o ns hi p t o A R R Y- 3 8 2 b y S O C, P T a n d ma xi m u m se verit y  
•  T E S A Es  wit h sus pecte d relati o ns hi p t o pe m br oliz u ma b b y S O C, P T a n d ma xi m u m 
se verit y  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
4 3  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
•  T E A Es, re gar dless of ca usalit y, t hat le d t o disc o nti n uati o n of st u d y dr u g, b y S O C a n d P T 
•  Treat me nt -relate d T E A Es wit h sus pecte d relati o ns hi p t o A R R Y - 3 8 2 lea di n g t o st u d y 
dr u g disc o nti n uati o n b y S O C a n d P T 
•  Treat me nt -relate d T E A Es wit h sus pecte d relati o ns hi p t o pe m br oliz u ma b lea di n g t o st u d y 
dr u g disc o nti n uati o n b y S O C a n d P T 
•  T E A Es t hat le d t o d ose r e d ucti o n i n A R R Y - 3 8 2 b y S O C a n d P T 
•  T E A Es t hat le d t o  d ose i nterr u pti o n / dela y of A R R Y - 3 8 2 b y S O C a n d P T 
•  T E A Es t hat le d t o  d ose i nterr u pti o n / dela y of pe m br oliz u ma b b y S O C a n d P T 
•  N o n -seri o us T E A Es, re g ar dless of ca usalit y, b y S O C a n d P T 
•  T E A Es t hat res ulte d i n d eat h o n st u d y or wit hi n 3 0 da ys of last st u d y treat me nt b y S O C 
a n d P T 
Se parate listi n gs f or A Es, seri o us A Es ( S A Es), A Es re q uiri n g d ose i nterr u pti o n, A Es lea di n g t o 
a n y st u d y dr u g disc o nti n uati o n, a n d deat h rec or d e d d uri n g t he st u d y will be pr o vi de d. 
All A Es a n d t heir attri b utes will be prese nte d i n d ata li sti n gs s orte d b y patie nt i de ntifier, A E a n d 
date of o nset of t he A E. 
7. 6. 5  
Cli nic al L a b or at or y E v al u ati o ns 
Re q uire d  he mat ol o g y,  c oa g ulati o n,  cli nic al  c h e mistr y , t h yr oi d  pa nel a n d  uri nal ysis  tests  are  
descri be d i n T a ble  9 of t he pr ot oc ol.  H e mat ol o g y, cli nical c he mistr y, c oa g ulati o n , t h yr oi d pa nel 
a n d uri nal ysis test res ults will be prese nte d usi n g t he I nt er nati o nal S yste m of U nits ( SI u nits) a n d, 
w here a p pr o priat e, will be gra de d usi n g N CI C T C A E, Versi o n 4. 0 3.  
F or la b orat or y dat a, baseli ne is t he  last a vaila ble assess me nt perf or me d pri or t o  t he treat me nt start 
date/ti me . If m ore t ha n o ne val ue is a vaila ble, pri orit y is gi ve n t o t he ce ntral assess me nt vers us t he 
l ocal assess me nt. If m ore t ha n o ne ce ntral sa m ple is a vaila ble, pri orit y is gi ve n t o t he assess me nt 
mar ke d as U nsc he d ul e d or Re peat assess me nt. Patie nts w h o start treat me nt a n d disc o nti n ue fr o m 
t he st u d y o n t he sa me da y ma y ha ve 2 differe nt sets of data c ollecte d o n st u d y da y 1, o ne bei n g 
re p orte d t o t he c ycle 1 d a y 1 visit, t he ot her re p orte d t o t he E O T visit. Data re p orte d at t he E O T 
visit are n ot eli gi ble f or b aseli ne selecti o n.  
T he f oll o wi n g la b orat or y para meters will be s u m marize d b y C T C A E gra d e:  
•  He mat ol o g y :  
He m o gl o bi n (a ne mia/ he m o gl o bi n i ncrease d), Platelets ( platelet c o u nt decreas e d), W B C 
( w hite  bl o o d  cell  decrease d/i ncreas e d),  Ne utr o p hils  ( ne utr o p hil  c o u nt  decreas e d),  
Ly m p h oc ytes (l y m p h oc yte c o u nt i ncrease d/ decrease d). 
•  C he mistr y:  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
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Versi o n 1. 0  
4 4  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
Al b u mi n  ( h y p oal b u mi ne mia),  Al kali ne  p h os p hatase  ( A L P) (al kali ne  p h os p hatas e  
i ncreas e d), Ala ni n e ami n otra nsferase (A L T ) ( A L T i ncrease d), A s part ate ami n otra nsferase 
(A S T ) ( A S T  i ncrease d),  Total  bilir u bi n  ( T B L) ( bl o o d  bilir u bi n  i ncrease d),  Creati ni ne  
(creati ni ne i ncreas e d), C orrect e d calci u m  ( h y p ocalce mia/ h y percal ce mia), Creati ne Ki nase 
( C P K  i ncrease d), Gl uc ose  ( h y p o gl yce mia/ h y per gl yce mia), A m ylas e  (s er u m  a m ylase  
i ncreas e d), Li p ase  (li pase  i ncreas e d),   P h os p hate ( h y p o p h os p h ate mia),  Ma g nesi u m  
( h y p o ma g nese mia/ h y per ma g nese mia),  P otassi u m  ( h y p o kale mia/ h y per kale mia),  S o di u m  
( h y p o natre mia/ h y per natr e mia). 
•  C oa g ulati o n: I N R (I N R i ncreas e d), P T T or a P T T ( Acti vate d p artial t hr o m b o plasti n, ti me 
pr ol o n ge d) 
T he f oll o wi n g r ules will be use d f or gra di n g ele v ate d gl uc ose: 
•  If a gl uc ose val ue f alls wit hi n n or mal ra n ges it s h o ul d be gra de d as zer o, irres pecti ve of 
fasti n g stat us.   
•  If f asti n g stat us is u n k n o w n a n d t h e res ult falls wit hi n t he ra n g es f or h y per gl yce mia gra des 
1 or 2, gra de s h o ul d b e set t o missi n g. 
•  If fasti n g stat us is k n o w n a n d fasti n g di d n ot occ ur, a n d t he res ult falls wit hi n t he ra n g es f or 
h y per gl yce mia gra d es 1 or 2, gra de s h o ul d b e set t o 0. 
T he f oll o wi n g la b orat or y para meters will be s u m marize d b y n or m al ra n ge:  
•  He mat ol o g y:  
He mat ocrit , R B C, M o n oc ytes (a bs ol ute), E osi n o p hils (a bs ol ute), Bas o p hils (a bs ol ute). 
•  C he mistr y:  
Bicar b o nate ( C O 2), B U N or urea , C hl ori de, Gl uc ose ( n o n -fasti n g), L D H, T otal pr otei n, 
Direct bilir u bi n . 
•  Uri nal ysis:  
S pecific gra vit y, Gl uc os e, Ket o nes, Bl o o d, Nitrite, Le u k oc ytes. 
•  T h yr oi d pa nel:   
T h yr oi d- Sti m ulati n g H or m o ne ( T S H)  
Trii o d ot h yr o ni ne ( T 3), fr ee 
T h yr o xi ne ( T 4), free 
T he C orrect e d  Calci u m will be deri ve d fr o m Calci u m a n d Al b u mi n res ults as per t he f oll o wi n g 
f or m ula:  
C orrecte d calci u m ( m m ol/ L) = [ 4 *cal ci u m( m m ol/ L) – 0. 8 *( 0. 1 *al b u mi n( g/ L) – 4)]/ 4  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
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Versi o n 1. 0  
4 5  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
T he n or mal ra n g e of t he Calci u m will be use d as n or mal ra n ge f or C orrect e d Calci u m.  
T he  f oll o wi n g s u m maries will be pr o d uce d f or t he he mat ol o gy, c oa g ulati o n, cli nical c he mistr y, 
t h yr oi d pa nel a n d uri nal ysis la b orat or y data ( b y l a b orat or y para meter): 
•  S hift ta bles usi n g C T C A E gra des t o c o m p are b as eli ne t o t he w orst p ost -baseli ne val ue f or 
la b orat or y  para meters  wit h  C T C A E  gra des.  F or  t he  la b orat or y  p ara m eters  li ke  bl o o d  
gl uc ose w her e patie nts ca n be gra d e d f or d ecreas e d or i ncrease d v al ues, t he w orst p ost -
baseli ne  C T C A E  gra de  will  be  prese nte d  f or  decrease  a n d  i ncreas e  se paratel y  (e. g.  
h y per g l yce mia a n d h y p o gl yce mia). I n t he des cri pti o n of w orst gra de i ncrease, a d ecrease of 
a gra de > = 1 will be des cri be d as gra d e 0. T he reci pr ocal will be a p plie d f or gra de decrease 
cate g orizati o n.  
•  S hift ta bles usi n g l o w, n or mal, hi g h (as well as l o w a n d hi g h c o m bi ne d) classificati o ns t o 
c o m pare b aseli ne t o t he w orst p ost -baseli ne val u e f or la b orat or y para meters w here C T C A E 
gra des are n ot defi ne d. 
•  T he f oll o wi n g listi n gs will be pr o d u ce d f or t he la b orat or y d ata f or all la b orat or y para meters 
w here C T C A E  gr a des ar e defi ne d:  
­  Listi n g  of  all  la b orat or y  data  wit h  val ues  fl a g ge d  t o  s h o w  t he  c orres p o n di n g  
C T C A E  gra des a n d t he classificati o ns relati ve t o t he la b orat or y refere n ce ra n ges.  
­  Listi n g of patie nts wit h la b orat or y a b n or malities of C T C A E  gra de 3 or 4. 
Ser ol o g y test res ults will be s u m marize d.  
All la b test res ults will b e pr ese nte d i n listi n gs s orte d b y  p atie nt i de ntifier, la b test , a n d d ate/ti me 
of c ollecti o n. Val ues o utsi de la b orat or y n or m al ra n ges will be fla g ge d w h ere a p pr o pri ate.  
He p atic To xicit y  
He patic t o xicit y will be assesse d base d o n t he f oll o wi n g Li ver F u ncti o n Tests ( L F Ts): A L T, A S T, 
A L P , a n d T B L . 
L F Ts will  be s u m marize d as f oll o ws: 
•  Fre q ue nc y  c o u nts  a n d  p erce nt a ges  of  p atie nts  ha vi n g  a  ne wl y  occ urri n g  val ue  i n  t he  
cate g ories i n Ta bl e 3 will be pr o vi de d. 
I n a d diti o n, a listi n g of all L F Ts val ues f or patie nts ha vi n g a n e wl y occ urri n g val ue i n t he cate g ories 
prese nte d i n Ta ble 3  will be pr o vi de d.  
 
 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
4 6  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
Ta bl e 3: 
H e p ati c To xi cit y C rit e ri a  
P ar a meter  
Criteri o n  
A L T  
> 3 x U L N; > 5 x U L N; > 8 x U L N; > 1 0 x U L N; > 2 0 U L N  
A S T  
> 3 x U L N; > 5 x U L N; > 8 x U L N > 1 0 x U L N; > 2 0 U L N  
A T ( A L T or A S T)  
> 3 x U L N; > 5 x U L N; > 8 x U L N > 1 0 x U L N; > 2 0 U L N  
T B L  
> 1. 5 x U L N, > 2 x U L N  
A L P  
> 2 x U L N, > 3 x U L N  
A T & T B L  
A T > 3 x U L N & T B L > 2 x U L N;  
A T > 5 x U L N & T B L > 2 x U L N;  
A T > 1 0 x U L N & T B L > 2 x U L N  
A L P & T B L  
A L P > 3 x U L N & T B L > 2 x U L N  
A T & T B L & A L P  
A T > 3 x U L N & T B L > 2 x U L N & A L P < 2 x U L N  
7. 6. 6  
Pre g n a nc y Tests  
Res ults of all pre g na nc y t ests will be prese nte d i n a data listi n g. 
7. 6. 7  
Vit al Si g ns  a n d B o d y Me as ure me nts  
T he f oll o wi n g criteri a defi ne cli nicall y n ota ble vit al si g n a b n or malities:  
Cli nic all y n ot a ble ele v ate d v al ues  
•  S yst olic Bl o o d Press ure ( B P ): ≥ 1 6 0 m m H g a n d a n i ncreas e ≥ 2 0 m m H g fr o m baseli ne 
•  Diast olic B P: ≥ 1 0 0 m m H g a n d a n i ncreas e ≥ 1 5 m m H g fr o m baseli ne 
•  Heart rat e (c ollect e d as p ulse rate i n t he vital si g ns e C R F): ≥ 1 2 0 b p m wit h i ncrease fr o m 
baseli ne of ≥1 5 b p m 
•  Wei g ht: i ncreas e fr o m baseli ne of ≥ 1 0 % 
•  B o d y te m perat ure [ C]: ≥ 3 7. 5 C 
Cli nic all y n ot a ble l o w v al ues  
•  S yst olic B P: ≤ 9 0 m m H g wit h decrease fr o m ba seli ne of ≥ 2 0 m m H g  
•  Diast olic B P: ≤ 5 0 m m H g wit h decrease fr o m bas eli ne of ≥ 1 5 m m H g  
•  Heart r ate (c ollecte d as p ulse rate i n t he vital si g ns e C R F): ≤ 5 0 b p m wit h decrease fr o m 
baseli ne of ≥ 1 5 b p m 
•  Wei g ht: ≥ 2 0 % decr eas e fr o m baseli ne  
•  B o d y te m perat ure [ C]: ≤ 3 6 C 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
4 7  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
N u m ber a n d per ce nta g e of patie nts wit h at least o ne p ost -baseli ne vital si g n a b n or malit y will be 
s u m marize d. 
Descri pti ve statistics will be ta b ulate d f or baseli ne a n d c ha n ge fr o m baseli ne t o w orst p ost -baseli ne 
val ue ( b ot h dire cti o ns) f or eac h vital si g n para met er.  
Patie nts wit h cli nicall y n ota ble vital si g n a b n or malities  will be liste d. All vital si g n assess me nts  
will be liste d b y patie nt a n d vital si g n para m eter.  Cli nicall y n ota ble val ues will als o be fla g g e d i n 
t his listi n g. 
7. 6. 8  
E C G  
P ote ntial effects of treat me nt wit h st u d y dr u g o n E C G para m eters will be assesse d b y E C G i nter v al 
a nal ysis of h eart rate,  p ulse rate,  Q R S, Q T, a n d Q T i nter v al c orrecte d  f or h eart  rate ( Q T c). 
Tri plicate  meas ure m e nts  will  be  o bt ai ne d  at  eac h  ass ess me nt  acc or di n g  t o  t he  s c he d ule  of  
assess me nts i n t he pr ot oc ol. Res ults fr o m tri plicate rea di n gs will be a v era g e d.  
T he a vera ge of t he m ac hi ne -rea d tri plicate E C G meas ure m e nts c ollecte d cl osest t o b ut pri or t o t he 
first  d ose  of  st u d y  dr u g  will  ser ve  as eac h  patie nt’s  Baseli ne -Q Tc  v al ue  f or  all  p ost - d ose 
c o m paris o ns. T he Q T c F data c ollecte d o n t h e e C R F pa ge will be use d i n t he s u m mar y.  
Data fr o m E C G s will be liste d, n ota ble val ues will be fla g g e d , a n d a n y ot her i nf or mati o n c ollect e d 
will be liste d as a p pr o pri ate. T he f oll o wi n g s u m m aries will be pr o vi de d f or eac h a p plica ble E C G 
para meter:  
•  Fre q ue nc y c o u nts a n d p erce nt a ges of p atie nts ha vi n g n ota ble E C G val ues acc or di n g t o 
Ta ble 4 . 
•  F or eac h Q T i nter val ( Q T, Q Tc F), s hift ta bles b ase d o n n ota ble Q T i nter val cate g ories 
( ≤4 5 0, > 4 50 - ≤4 8 0, > 4 8 0 - ≤5 0 0, > 5 0 0 ms ) at baseli ne t o t he w orst p ost -baseli ne val ue 
o bser ve d. 
Ta bl e 4: 
C rit e ri a f o r N ot a bl e E C G C rit e ri a  
P ar a meter  
Criteri o n  
Q T, Q Tc F  
i ncrease fr o m baseli ne > 3 0 ms 
 
i ncrease fr o m baseli ne > 6 0 ms 
 
ne w > 4 5 0 ms  
 
ne w > 4 8 0 ms  
 
ne w > 5 0 0 ms  
Heart rate  
I ncrease fr o m baseli ne > 2 5 % t o a val ue > 1 0 0 b p m 
 
Decrease fr o m baseli ne > 2 5 % a n d t o a val ue < 5 0 b p m  
 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
4 8  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
7. 6. 9  
P h ysic al E x a mi n ati o ns 
P h ysical e xa mi nati o n dates will be prese nte d i n a data listi n g. A n y a b n or mal fi n di n gs were t o 
ha ve bee n re p orte d as A Es a n d will be re p ort e d i n t he a p pr o priat e A E listi n gs a n d s u m mar y 
ta bles. 
7. 6. 1 0  
E aster n C o o per ati ve O nc ol o g y Gr o u p Perf or m a nce St at us P erf o r m a nce St at us  
Easter n C o o per ati ve O n c ol o g y Gr o u p (E C O G ) perf or ma nce stat us is use d t o assess t he p h ysical 
healt h of p atie nts, a n d ra n ges fr o m 0 ( m ost acti ve) t o 5 ( d ea d). Fre q ue n c y c o u nts a n d perce nta ges 
of patie nts i n eac h s c ore cate g or y will be pr o vi de d b y assess me nt visit . 
I n a d diti o n, t he E C O G s hift fr o m baseli ne t o hi g hest sc ore d uri n g t he p ost-b aseli ne peri o d will be 
s u m marize d.  
E C O G perf or ma nce stat us  at eac h ti me p oi nt will be liste d.  
7. 6. 1 1  
Cli nic all y Si g nific a nt Pr oce d ures  
All cli nicall y si g nifica nt pr oce d ur es relat e d t o ca n cer w hile o n st u d y (fr o m first d ose t hr o u g h e n d 
of st u d y) will be liste d.  
7. 6. 1 2  
Tr a nsf usi o n 
D ata o n tra nsf usi o ns of bl o o d pr o d ucts recei ve d w hile o n st u d y will be liste d.  
7. 7  
P h ar m ac o ki netic A n al ysis  
T he P har mac o ki n eti c A n al ysis Set will be use d f or all P K a nal ysis, listi n gs a n d fi g ures.  C 1 D 1 is 
defi ne d as si n gle d ose (i.e., first d ose), a n d C 2 D 1 is defi ne d as stea d y stat e.  
7. 7. 1  
Pl as m a C o nce ntr ati o ns of A R R Y - 3 8 2 a n d its t h ree met a b olites ( A R 0 0 4 6 9 0 9 9, 
A R 0 0 4 6 9 1 0 0 a n d A R 0 0 4 7 0 8 7 0) 
Plas ma c o nce ntr ati o ns of A R R Y - 3 8 2 a n d its t hree meta b olites ( A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0 a n d 
A R 0 0 4 7 0 8 7 0) will be c ollecte d a n d t he n d eter mi n e d usi n g a vali date d bi oa nal ytical met h o d at 
t he ti me p oi nts as s pecifie d i n pr ot oc ol. All plas ma c o nce ntrati o n val ues f or eac h p atie nt i n t he 
P K set will be i ncl u de d i n t he bi oa nal ytical plas m a c o nce ntrati o n listi n gs.  I n di vi d ual 
c o nce ntr ati o n rec or ds will be fla g ge d f or t he affecte d visit if a n y of t he f oll o wi n g occ ur: 
a. Patie nt ha d v o miti n g  wit hi n 4 h o urs f oll o wi n g st u d y  dr u g a d mi nistrati o n o n t he da y of 
series P K sa m pli n g. 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
4 9  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
b.  Plas ma le vels were n ot c o nsi dere d t o b e at stea d y -state (i.e. d osi n g was n ot perf or m e d f or 
at least 4 c o nsec uti ve da ys pri or t o C 2 D 1).  
c. S u bject recei v e d a hi g her or l o wer d ose c o m pare d t o pla n ne d treat me nt .  
d.  P K sa m pli n g ti me was o utsi de t he all o w e d wi n d o w or t he el a pse d ti me was n ot calc ula bl e.   
T he plas ma c o nce ntrati o ns of A R R Y -3 8 2 a n d its t hree meta b olites ( A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0 
a n d A R 0 0 4 7 0 8 7 0) will  be s u m marize d b y p hases, d ose le vels a n d c o h orts f or all n o mi nal ti me 
p oi nts, i ncl u di n g pre d ose (tr o u g h) c o nce ntrati o ns f or C 1 D 1 5, C 3 D 1, C 4 D 1, C 5 D 1 a n d C 6 D 1 , 
usi n g t he f oll o wi n g descri pti ve statistics:  n ( n u m ber of patie nts wit h n o n -missi n g val ues), m 
( n u m ber of n o n-zer o c o n ce ntrati o ns), arit h metic mea n, sta n dar d d e viati o n, c oefficie nt of v ariati o n 
( C V),  ge o metric  mea n,  ge o metric  sta n dar d  de vi ati o n,  ge o metric  C V,  mi ni m u m,  me dia n  a n d  
ma xi m u m.  A n  i n di vi d ual  c o nce ntr ati o n -ti me  data  p oi nt  be  e xcl u d e d  fr o m  t he  calc ulati o n  of  
s u m mar y statistics if a n y of t he a b o ve fla gs [a-d] a p pl y. F or eac h ti me p oi nt, statistical val ues will 
o nl y be calc ulate d if at least t w o -t hir ds of t he i n di vi d ual c o nce ntrati o n data meas ure d are a b o ve 
t he li mit of q ua ntitati o n. B L Q s will be set t o zer o f or t he calc ulati o n  of arit h metic mea n, S D, C V,  
mi ni m u m, me dia n a n d ma xi m u m.  F or t he calc ulati o n of ge o metric m ea ns a n d ge o m etric C V s, 
B L Q c o nce ntrati o ns will be re place d b y ½ L L O Q.   W he n greater t ha n o ne-t hir d of data p oi nts are 
B L Q, t he mea ns, sta n dar d de viati o ns a n d C Vs will be re p orte d as n ot calc ulate d ( N C). W he n all 
data p oi nts are B L Q, t he mea n will be re p orte d as B L Q a n d sta n dar d de viati o ns  a n d C Vs will be 
re p orte d as N C. If t her e are less t ha n 3 val ues f or calc ulati o n of sta n dar d de viati o n or C V, t he val u e 
will be re p orte d as N C.  
T he ge o metric  mea n wit h sta n dar d de viati o n plas ma c o nce ntrati o n -v ers us -ti me pr ofiles will be 
prese nte d gra p hi call y f or eac h a n al yt e usi n g b ot h li near a n d se mi -l o garit h mi c scales o n C 1 D 1 a n d 
C 2 D 1 f or P hase 1 b/ Part A a n d P hase 2 . Ge o metric mea n  plas ma c o nce ntrati o ns will o nl y be pl otte d 
f or  a  s pecifi c  ti me  p oi nt  if  at  least  t w o-t hir ds  of  t he  c o nce ntrati o ns  are  a b o v e  t he  li mit  of  
q ua nti tati o n a n d t he act ual ti me of sa m ple c ollecti o n was wit hi n t he pr ot oc ol-s pecifi e d  ti me 
wi n d o w. I n di vi d ual plas ma c o nce ntrati o n -ti me pr ofiles will als o b e prese nte d gra p hicall y usi n g 
li near a n d s e mi-l o garit h mic scales b y st u d y da y. F or ease of pres e ntati o n, n o mi nal ti me will be 
use d t o prese nt r es ults i n s u m mar y a n d act u al ti me f or i n di vi d ual fi g ures. 
7. 7. 2  
Pl as m a P h ar m ac o ki netic P ar a meters f or A R R Y - 3 8 2 a n d its t hree met a b olites 
( A R 0 0 4 6 9 0 9 9, A R 0 0 4 6 9 1 0 0 a n d A R 0 0 4 7 0 8 7 0) 
P K para meters  f or patie nts i n t he P K set will be deri ve d f or A R R Y -3 8 2 a n d its t hree meta b olites 
( A R 0 0 4 6 9 0 9 9,  A R 0 0 4 6 9 1 0 0  a n d  A R 0 0 4 7 0 8 7 0) o n  C 1 D 1  a n d  C 2 D 1  w he n  p ossi ble  a n d  
a p pr o priate. P ara m eters ma y  i ncl u de b ut n ot li mite d t o A U Cτ, Cma x , Tma x , Ctr o u g h, acc u m ulati o n 
rati o, a n d meta b olite-t o-p are nt r ati o. 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
5 0  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
T he  i n di vi d ual  plas ma  c o nce ntrati o n -ti me  dat a  f or  eac h  a nal yte  will  be  e val uate d  wit h  
n o nc o m part me ntal a n al ysis ( N C A ) usi n g P h oe ni x Wi n N o nli n , Versi o n 8. 0 or hi g her. A ct ual 
bl o o d c ollecti o n ti mes a n d d os es will b e use d f or P K calc ulati o ns. All B L Q val ues b ef ore t he 
o bser ve d ma xi m u m plas ma c o nce ntr ati o n ( Cma x ) will be set t o 0; all B L Q val ues after C ma x  will 
be c o nsi dere d as missi n g.  T he A U C para meters will be calc ulate d acc or di n g t o t he li near -u p l o g -
d o w n  tra pez oi dal  r ule.  A d diti o nal  P K  para met ers  ma y  be  cal c ulate d  at  t he  discreti o n  of  t he  
p har mac o ki neticist.  
All P K para meter val ues will be prese nt e d i n data listi n gs b y p hases, d ose le vels a n d c o h orts f or 
a nal yte, c y cle a n d st u d y da y. Eac h p ara m eter will be s u m marize d i n ta bles b y p hases, d ose le vels 
a n d c o h orts f or  a nal yte, c ycle a n d st u d y da y usi n g t he f oll o wi n g descri pti ve statistics:  n, arit h metic 
mea n, sta n dar d d e viati o n, C V, ge o metric mea n, g e o metric C V, mi ni m u m, me dia n a n d ma xi m u m. 
S u m mar y  descri pt i ve  statistics  f or  i n-te xt  s u m mar y  ta bles  will  i ncl u de  ge o metric  mea n  wit h  
ge o metric C V f or A U C, C ma x , a n d R A U C . F or Tma x  a n d t1/ 2  val ues, me dia n, mi ni m u m a n d ma xi m u m 
will be prese nte d. P har m ac o ki netic para meters  will be e xcl u de d fr o m  t he calc ulati o n of s um mar y 
statistics if a n y of t he a b o ve fla gs [a-c] a p pl y. 
 
 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
5 1  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
Ta bl e 5: 
D efi niti o ns of P h a r m a c o ki n eti c P a r a m et e rs  
P K P ar a met er  
Defi niti o n  
C 1 D 1  
A U C 0- 8 
Area  u n der  t he  plas ma  c o nce ntrati o n -ti me  c ur ve  fr o m  zer o  t o  8 h o urs  after  dr u g  
a d mi nistrati o n  
A U C last 
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m zer o t o t he last meas ura ble ti me 
p oi nt  
C ma x  
Ma xi m u m o bser ve d plas ma c o nce ntrati o n after dr u g a d mi nistrati o n  
T ma x  
Ti me t o reac h C ma x   
T last 
Ti me of last P K sa m ple  
M R
C ma x  
Rati o of C ma x  val ues of t he meta b olite c o m pare d t o pare nt , c orrecte d f or m olec ular 
wei g ht,  
M R
A U Clast  
Rati o of A U C last val ues of t he meta b olite c o m pare d t o pare nt , c orrecte d f or m olec ular 
wei g ht,  
C 2 D 1  
A U C 0- 8,ss 
Area  u n der  t he  plas ma  c o nce ntrati o n -ti me  c ur ve  fr o m  zer o  t o  8 h o urs  after  dr u g  
a d mi nistrati o n at stea d y -state 
A U C last,ss 
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m zer o t o t he last meas ura ble ti me 
p oi nt at stea d y -state 
A U C ta u,ss 
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve o ver a d osi n g i nter val at stea d y-state 
T o esti mate A U C ta u,ss, t he c o nce ntrati o n meas ure d at pre d ose o n stea d y state (C 1 D 1 5 f or 
P hase 1 b/ Part A a n d P hase 2)  will be i m p ute d as t he c o nce ntrati o n at t he e n d of t he d osi n g 
i nter val (i.e., 1 2 or 2 4 h o urs, as a p pr o priate) ass u mi n g stea d y-state has bee n attai ne d 
C ma x,ss  
M a xi m u m o bser ve d plas ma c o nce ntrati o n after dr u g a d mi nistrati o n  
C tr o u g h,ss 
Meas ure d c o nce ntrati o n at t he e n d of a d osi n g i nter val at stea d y -state 
T ma x,ss  
Ti me t o reac h C ma x  
T last,ss 
Ti me of last P K sa m ple  
M R
C ma x,ss  
Rati o of C ma x,ss  val ues of t he meta b olite c o m pare d t o pare nt , c orrecte d f or m olec ular 
wei g ht,  
M R
A U Cta u,ss  
Rati o of A U C ta u,ss val ues of t he meta b olite c o m pare d t o pare nt, c orrecte d f or m olec ular 
wei g ht,  
R A U C  
Acc u m ulati o n rati o, calc ulate d as: A U C 0- 8,ss  / A U C0- 8 
R C ma x  
Acc u m ulati o n rati o, calc ulate d as: C ma x,ss  / Cma x  
 
 
 
  
C C
I


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
5 2  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
7. 9  
I nteri m A n al ysis 
N o f or mal i nteri m a nal ysis is pla n ne d i n t his st u d y.  


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
5 3  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
8. 0  
D A T A A N D A N A L Y SI S Q U A LI T Y A S S U R A N C E  
T his pr ot oc ol was c o n d ucte d u n der t he s p o ns ors hi p of Arra y Bi o P har ma. Pers o n nel wit hi n Arra y 
Bi o P har ma or C R O desi g nee pr o vi de d statistical a n d data ma na ge me nt i n p ut f or t he desi g n of t he 
cli nical trial pr ot o c ol; data ma na ge m e nt, statistical a nal ysis a n d g e nerati o n of ta bles, listi n gs a n d 
fi g ures; a n d me dical writi n g s u p p ort f or t he cli nical st u d y re p ort.   
All parties me nti o ne d a b o ve will w or k dili ge ntl y a n d c olla b orati vel y t o e ns ure t hat data c ollecti o n 
a n d  a n al ysis  f or  t his  st u d y  ar e  of  t he  hi g hest  q ualit y.  T his  will  be  acc o m plis he d  t hr o u g h  
pr o gra m me d e dit c hec ks, q ualit y c o ntr ol  pr ocess es, a n d cli nical a n d statistical re vie w of dat a 
dis pla ys. Q ualit y a n d acc urac y of statistical a n al yses will be verifie d t h o u g h esta blis he d statistical 
pr o gra m mi n g vali dati o n pr ocesses. 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
5 4  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
9. 0  
R E F E R E N C E S  
 
1.  E. A. Eise n ha uer. Ne w res p o nse e val uati o n criteria i n s oli d t u m ors: Re vise d R E CI S T 
g ui deli ne ( versi o n 1. 1) 
2.  Je d d D. W olc h o k. G ui d eli nes f or t he E val u ati o n of I m m u ne T h era p y Acti vit y i n S oli d 
T u m ors: I m m u ne- R elate d Res p o nse Criteria  
3.  Si m o n R. O pti mal t w o -sta ge desi g ns f or P has e II Cli nical Trials. C o ntr ol Cli n Trials 
1 9 8 9; 1 0( 1): 1- 1 0.  
4.  Cl o p per CJ, Pears o n E S. T he use of c o nfi de nce or fi d ucial li mits ill ustrate d i n t he case of 
t he bi n o mial. Bi o metri ka 1 9 3 4; 2 6( 4): 4 0 4- 1 3 


A R R Y -3 8 2 ( C S F -1 R i n hi bit or)  
 
Arr a y Bi o P h ar m a I nc.  
A R R A Y -3 8 2 -2 0 1 St atistic al A n al ysis Pl a n  
 
 
 
 
Versi o n 1. 0  
5 5  
C o nfi de ntial  
2 0 Fe br uar y 2 0 2 0  
1 0. 0  
S T A N D A R D  O P E R A TI N G P R O C E D U R E S, F O R M S A N D W O R K 
I N S T R U C TI O N S 
Arra y Bi o p har m a S O Ps will be utilize d.