Clinical trial NCT05177770
Conditions: Metastatic Castration-resistant Prostate Cancer Prostate Cancer
Keywords: mCRPC metastatic castration-resistant prostate cancer prostate cancer CD-39 PD-1 A2a A2b SRF617 AB122 AB928 adenosine pathway cancer immunotherapy phase 2 efficacy checkpoint inhibitor adenosine receptor antagonist
Sponsor: Coherus Biosciences, Inc.
Start date: 2022-01-17; Completion date: 2023-04-05
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This trial will look at the safety and preliminary efficacy of SRF617 in combination with etrumadenant and zimberelimab in patients with metastatic castration-resistant prostate cancer (mCRPC).

Detailed description:
This is a phase 2, open-label, safety and preliminary efficacy trial in patients with mCRPC using the combination of SRF617, etrumadenant (AB928), and zimberelimab (AB122).

Arms: arm 1: All patients will receive SRF617 administered in combination with etrumadenant (AB928) and zimberelimab (AB122).
Interventions: intervention 1: SRF617 intervention 2: etrumadenant intervention 3: zimberelimab
Intervention descriptions: intervention 1: SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39. intervention 2: Etrumadenant is an A2aR and A2bR antagonist. intervention 3: Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Protocol documents:
Prot_000.pdf: 
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TRIAL PROTOCOL 
SRF617-201 
Protocol Title: 
A Phase 2 Trial of SRF617 in Combination With AB928 
(Etrumadenant) and AB122 (Zimberelimab) in Patients With 
Metastatic Castration-Resistant Prostate Cancer 
Protocol Number: 
SRF617-201 
Phase: 
2 
Date of Protocol: 
Version 1.1 30 July 2021 
Original: 
Version 1.0 25 May 2021 
IND: 
144,623 
Sponsor: 
Surface Oncology, Inc. 
50 Hampshire Street, Floor 8 
Cambridge, MA 02139 
Not for Distribution – Do Not Copy 
This trial protocol contains confidential information and is the proprietary property of 
Surface Oncology, Inc. The protocol is for use by the Principal Investigator and his/her designated 
representatives participating in this investigational trial. This protocol may not be copied or made available 
for review by an unauthorized person or firm without the prior written authorization of Surface Oncology, 
Inc. 
NCT #: NCT05177770


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INVESTIGATOR PROTOCOL APPROVAL 
 
I agree to the terms of this trial protocol. I will conduct the trial according to the procedures 
specified herein, and according to principles of Good Clinical Practice and local regulations and 
requirements. 
 
Institution/Clinic:   
Principal Investigator 
 
Printed Name:  
Signature:  
Date (dd/mm/yyyy):  
 


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SPONSOR PROTOCOL APPROVAL 
 
I have read this protocol and approve the design of this trial: 
 
Surface Oncology, Inc. 
  
Date 
 
30-Jul-21 | 18:00 EDT


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CONTACT INFORMATION 
 
Sponsor:  
Surface Oncology, Inc. 
50 Hampshire Street, Floor 8 
Cambridge, MA 02139 
Telephone: 617-714-4096 


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PROTOCOL SYNOPSIS 
Trial Title: 
A Phase 2 Trial of SRF617 in Combination With AB928 (Etrumadenant) and AB122 
(Zimberelimab) in Patients With Metastatic Castration-Resistant Prostate Cancer 
Protocol Number: SRF617-201 
Phase: 2 
Study Drugs: SRF617 in combination with etrumadenant (AB928) and zimberelimab (AB122) 
Trial Population: 
This open-label Simon 2-stage trial will enroll approximately 40 patients with metastatic 
castration-resistant prostate cancer (mCRPC) who have progressed on or after prior androgen 
receptor signaling inhibitor (ARSI) therapy. All patients will receive SRF617 in combination 
with etrumadenant and zimberelimab. 
Duration: 
Patients will continue to receive study drug for up to 2 years or until documented disease 
progression or unacceptable toxicity. Patients may remain on study drug longer than 2 years 
with agreement from the trial Investigator and Sponsor. All patients will have a Safety Follow-
up visit after the last dose of study drug (SRF617, etrumadenant, and/or zimberelimab). 
Trial Centers: 
Enrollment is anticipated at approximately 15 sites in the United States and Canada. 
Trial Design: 
This Phase 2, open-label, safety and preliminary efficacy trial in patients with mCRPC will 
employ a Simon 2-stage design with an integrated safety lead-in for the triplet combination of 
SRF617, etrumadenant, and zimberelimab. Cycles are 28 days in duration. Stage 1 will enroll 
approximately 17 patients, including the Safety Lead-in that will initially treat 6 patients. After 
the first 6 patients have been enrolled, enrollment will be paused until these patients have 
received 1 cycle of the triplet combination and the Safety Review Committee (SRC) has 
reviewed the aggregate safety data. Once the SRC deems it safe to proceed, an additional 
11 patients will be enrolled. Based on an evaluation of safety and response data, the trial will 
proceed to the Stage 2 expansion if ≥ 1 radiographic complete response (CR)/partial response 
(PR) or 2 prostate-specific antigen (PSA) responses (defined as a ≥ 50% decline [PSA50]) 
according to the Prostate Cancer Working Group 3 (PCWG3) criteria are observed in 
17 evaluable patients. An additional 23 patients will be enrolled in Stage 2 for further 
evaluation of the safety and efficacy of the combination. Tumor biopsies are optional; they will 
be performed to explore potential biomarkers of response to the combination in patients who 
consent to the procedure, who have non-bone metastases amenable to biopsy, and for whom the 
procedure is deemed safe. 
Safety Review Committee 
The SRC will be composed of a medical representative from the Sponsor, a Medical/Safety 
Monitor from the Contract Research Organization supporting the trial (if applicable), and all 


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Principal Investigators (or their specified delegates) at each of the enrolling sites. The SRC will 
meet regularly throughout the trial to review all available safety, pharmacokinetics (PK), and 
preliminary efficacy data. The SRC may recommend investigating intermediate doses or 
alternative schedules for administration of SRF617 to optimize combination dose 
determination. The SRC may recommend halting or stopping the trial at any time based on a 
comprehensive review of all clinical data.  
Stage 1 Safety Lead-in  
Once the first 6 patients in Stage 1 have received 1 cycle of the triplet combination, the SRC 
will review the aggregate safety data. To be considered evaluable for the Safety Lead-in, 
patients must have completed at least 50% of the prescribed doses of all 3 drugs during the 
review period (Day 1-28 = Cycle 1) and must not have discontinued treatment during Cycle 1 
for reasons other than drug-related adverse events (AEs). For example, patients who 
discontinued study treatment during Cycle 1 for progressive disease or for patient or physician 
preference but without experiencing a Grade ≥ 3 related toxicity would not be considered fully 
evaluable for the Safety Lead-in and would be replaced. A ‘related’ toxicity is defined as those 
toxicities assessed by the Investigator to be possibly, probably, or definitely related to any study 
drug.  
This analysis set will be used to assess the preliminary safety of the triplet therapy.  
The following safety stopping rule will also be applied during the Safety Lead-in: If 2 or more of 
these 6 patients experience a Grade ≥ 3 related AE (with the exception of toxicities listed in the 
table below), any treatment-related toxicity that causes the participant to discontinue treatment 
during Cycle 1, or prolonged delay (>14 days in initiating Cycle 2 due to toxicity), the trial will 
be halted for SRC review.  
Stopping Rule Exceptions 
The following Grade ≥ 3 toxicities considered at least possibly related to study treatment would not 
be considered to meet criteria for a safety stopping rule: 
Nausea 
Any Grade ≥ 3 event responding to supportive treatment within 3 days 
Vomiting 
Diarrhea 
Fatigue 
Grade ≥ 3 lasting < 7 days 
Asymptomatic 
amylase/lipase elevations  
Grade ≥ 3 lasting any duration if asymptomatic/ no clinical signs of 
pancreatitis 
Thyroid function 
abnormalities (eg, hypo- or 
hyperthyroidism)  
Grade ≥ 3 lasting any duration if can be controlled with treatment such 
as thyroid supplementation or beta blockade 
Rash 
Grade ≥ 3 recovering to Grade 1 with treatment (ie, steroids) within 
7 days 
Alopecia 
Grade ≤ 2 lasting any duration 
Non-hematologic 
laboratory abnormalities  
Clinically nonsignificant, treatable, or reversible laboratory 
abnormalities including liver function tests, electrolytes, uric acid, etc. 
Adverse Event Monitoring 
All patients will be monitored continuously for toxicity while on study drug. AE severity will 
be assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events 


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(NCI-CTCAE) version 5.0, or higher. If a patient has an AE of a particular severity or an AE at 
least possibly related to study drug, then dose modifications should be made according to the 
guidelines set forth in the trial protocol. 
Trial Objectives: 
Primary Objective:  
• To evaluate the preliminary efficacy of SRF617 administered in combination with 
etrumadenant and zimberelimab as determined by objective response and PSA decline  
• To evaluate the safety and tolerability of the combination 
Secondary Objectives:  
• To evaluate additional preliminary efficacy parameters of the combination including 
objective response rate (ORR), PSA response, clinical benefit, duration of response, and 
radiologic progression-free survival (PFS)  
• To evaluate the PK of SRF617 when administered in combination with etrumadenant 
and zimberelimab 
• To characterize additional safety parameters including development of antidrug 
antibodies (ADAs) and symptomatic skeletal events (SSEs) 
Exploratory Objectives: 
• Explore potential biomarkers of response and/or safety of the combination 
• Explore the effects of the triplet on peripheral blood immune cell subsets and circulating 
serum cytokines and chemokines  
• Explore the biological effects of the triplet on tumor cells and immune cell populations 
in the tumor microenvironment 
• Explore germline DNA polymorphic variations in relation to the PK, 
pharmacodynamics, safety, and/or preliminary efficacy  
• Explore correlations between prostate cancer biomarkers in tumors with biomarkers in 
serum in patients who undergo tumor biopsy  
• Explore correlations between prostate cancer biomarkers in tumors with clinical 
response parameters in patients who undergo tumor biopsy 
Trial Endpoints: 
Primary Endpoint: 
• The proportion of patients with a response, defined as PSA50 response (≥ 50% decline) 
and/or radiographic objective response of CR or PR per PCWG3 criteria  
• Incidence and severity of AEs 
Secondary Endpoints: 
• ORR per PCWG3 criteria, ORR per Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1, duration of response, disease control rate, PSA50 response, PSA decline 
≥ 30% (PSA30) response, time to PSA progression, radiographic PFS, and landmark 
PFS rate at 6 and 12 months 


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• Serum concentrations of SRF617 
• Percentage of patients with ADAs to SRF617  
• Incidence of SSEs 
Exploratory Endpoints: 
• Changes in selected blood and tumor tissue biomarkers  
• Germline DNA polymorphic sequence variations in relation to the PK, 
pharmacodynamics, safety, and/or preliminary efficacy of SRF617 
• Serum prostatic acid phosphatase (PAP) levels 
• PAP expression levels in tumors in patients who undergo tumor biopsy  
• Programmed death-ligand 1 (PD-L1) and CD39 expression levels in tumors in patients 
who undergo tumor biopsy 
Inclusion Criteria: 
All patients must meet the following criteria for inclusion: 
1. Males ≥ 18 years of age on the day of signing informed consent. 
2. Metastatic CRPC with castrate levels of testosterone (≤ 50 ng/dL or ≤ 1.7 nmol/L). 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 
4. Must have progressed (by PSA or radiologic criteria) during or following treatment with 
a novel ARSI (eg, abiraterone, enzalutamide, apalutamide, darolutamide), which may 
have been given for either hormone-sensitive prostate cancer or CRPC. 
5. Must have received 1 to 2 prior lines of taxane chemotherapy, unless the physician and 
patient believe the patient is medically ineligible or the patient refuses (ineligibility or 
refusal must be documented in the source documents). 
6. Must have progressed by PSA or radiologic criteria on or during last therapy for 
prostate cancer. 
7. Measurable or non-measurable disease as per radiographic evaluation. Lesions situated 
in a previously irradiated area are considered evaluable if progression has been 
demonstrated in such lesions since radiation. 
• Note: If disease is considered non-measurable, a minimum PSA of 1 ng/dL is 
required with at least 1 confirmed rise at a minimum of a 1-week interval. 
8. Washout period from the last dose of previous anticancer therapy (chemotherapy, 
biologic, or other investigational agent) to the first dose of study drug must be > 5 times 
the half-life of the agent or > 21 days, whichever is shorter. The washout period for 
palliative radiation (defined as ≤ 2 weeks of radiation) to non-central nervous system 
(CNS) disease is > 7 days. 
9. Resolution of non-immune-related AEs secondary to prior anticancer therapy 
(excluding alopecia and peripheral neuropathy) to Grade ≤ 1 per NCI-CTCAE 


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version 5.0 or higher, and complete resolution of immune-related AEs secondary to 
prior immunotherapy. 
• Note: Patients with the following clinically stable or clinically nonsignificant 
immune-related AEs are permitted: Controlled thyroid disorders, vitiligo, 
asymptomatic elevated amylase/lipase, type 1 diabetes on insulin, Grade ≤ 2 
controlled rash, Grade ≤ 2 electrolyte abnormalities on stable dose of 
supplementation. 
10. Adequate hematologic function, defined as absolute neutrophil count ≥ 1.5 × 109/L, 
hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 × 109/L. Transfusions are permitted to 
meet hemoglobin and platelet criteria. However, the patient must have a stable 
hemoglobin level and platelet count for ≥ 2 weeks prior to dosing without transfusion. 
11. Adequate renal function, defined as serum creatinine clearance ≥ 30 mL/min per 
Cockcroft-Gault formula. 
12. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 3 × ULN if elevated because of 
Gilbert’s syndrome, and ≤ 2 × ULN for patients with known liver metastases). 
13. Aspartate aminotransferase and alanine aminotransferase < 2.5 × ULN (< 5 × ULN if 
liver metastases present). 
14. Prothrombin time (PT) or international normalized ratio (INR) and activated partial 
thromboplastin time (aPTT) ≤ 1.5 × ULN unless the patient is receiving anticoagulant 
therapy, in which case PT/INR or aPTT must be within therapeutic range of intended 
use of anticoagulants. 
15. Willingness of male patients who are not surgically sterile to use medically acceptable 
methods of birth control for the duration of the study treatment period, including 
30 days after the last dose of SRF617, 30 days after the last dose of etrumadenant, or 
90 days after the last dose of zimberelimab, whichever is later; male patients must 
refrain from donating sperm for 4 months after the last dose of any study drug. Sexually 
active men, when having sexual intercourse with a female of reproductive potential, 
should use an efficient barrier contraceptive (condom plus spermicide); the respective 
partner should also use an additional efficient contraceptive method (eg, oral pills, 
intrauterine device, or diaphragm, and spermicide). 
16. Ability to adhere to the trial visit schedule and all protocol requirements. 
17. Institutional review board/independent ethics committee-approved informed consent 
form signed and dated by patient (or legally acceptable representative if applicable) 
before any Screening procedures are performed. 
Exclusion Criteria: 
Patients are to be excluded from the trial if they meet any of the following criteria: 
1. Currently participating in or has participated in a trial of an investigational device or has 
used an investigational device within 21 days before the first dose of study drug. 
2. Any component of small cell or neuroendocrine histology. 


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3. Previously received an anti-CD39 antibody, anti-CD39 targeted therapy, or other agent 
targeting the adenosine pathway. 
4. Prior treatment with programmed death-ligand 1 (PD-L1)/programmed death receptor-1 
(PD-1) inhibitors. 
5. Prior treatment with ≥ 3 lines of taxane chemotherapy administered as a single agent or 
as part of a combination regimen. 
6. Symptomatic or untreated brain metastases (including leptomeningeal metastases). 
Patients previously treated for brain metastases must be at least 4 weeks from 
completion of radiation treatment with follow-up imaging showing no progression. 
7. Current pneumonitis with or without steroid requirement or history of pneumonitis 
requiring steroids. 
8. Another malignancy other than prostate within 2 years of trial entry, except for those 
with a low risk of spreading or negligible risk of death such as non-melanoma skin 
cancer or Ta superficial bladder cancer. 
9. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with 
use of disease modifying agents, corticosteroids, or immunosuppressive drugs). 
10. Medical conditions requiring chronic steroid (ie, > 10 mg/day of prednisone or its 
equivalent). 
• Note: Replacement therapy (eg, levothyroxine, insulin, or physiologic 
corticosteroid replacement therapy for thyroid, adrenal, or pituitary insufficiency) is 
allowed. 
11. Concomitant therapy with agents that may have potential drug-drug interactions with 
etrumadenant: 
a) Known P-glycoprotein substrates with a narrow therapeutic window, administered 
orally (eg, digoxin) within 4 weeks or 5 half-lives of the drug (whichever is shorter) 
prior to initiation of study treatment. 
b) Known strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, 
phenobarbital, and St. John’s Wort) and strong CYP3A4 inhibitors (eg, 
clarithromycin, itraconazole, ketoconazole, posaconazole, telithromycin, and 
voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior 
to initiation of study treatment. 
c) Known breast cancer resistance protein substrates with a narrow therapeutic 
window, administered orally (eg, prazosin, rosuvastatin) within 4 weeks or 5 half-
lives of the drug (whichever is shorter) prior to initiation of study treatment. 
d) Additional substrates, inhibitors, and inducers with the potential for drug-drug 
interactions with etrumadenant within 4 weeks or 5 half-lives of the drug 
(whichever is shorter) prior to initiation of study treatment. Refer to Appendix 1 
and the following: https://www.fda.gov/drugs/drug-interactions-labeling/drug-
development-and-drug-interactions-table-substrates-inhibitors-and-inducers. 


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12. History of Grade ≥ 3 allergic or anaphylactic reaction to any monoclonal antibody 
therapy, any excipient in the study drugs, or fusion proteins. 
13. Prior hematopoietic stem cell or solid organ transplant. 
14. Known current or prior infection with HIV, hepatitis B virus (HBV), or current 
infection with hepatitis C virus (HCV).  
• Exception: Controlled active HBV or fully treated HCV infection is permitted. 
Antiviral therapy as per local standard of care should be continued. 
− Controlled disease is considered HBV DNA < 500 IU/mL during the Screening 
Period with willingness to continue antiviral treatment during the length of the 
trial. The patient must be on anti-HBV treatment (per local standard of care; eg, 
entecavir) for a minimum of 14 days prior to trial entry. 
− For patients with HCV, only cured disease or HCV considered fully treated and 
no longer requiring antiviral therapy for control is permitted.  
− No co-infection with HCV and HBV is allowed. HCV and HBV co-infection is 
defined as HCV RNA positive and hepatitis B surface antigen (HBsAg) positive 
and is excluded. However, a patient who is HCV antibody positive, hepatitis B 
core antibody positive, but negative HBsAg is not considered co-infection and is 
permitted. 
15. Administration of a live attenuated vaccine within 6 weeks before the first dose of study 
drug. 
• Exception: Health Authority approved COVID-19 vaccines are permitted. 
16. Baseline QT interval corrected (QTc) with Fridericia’s method 
(QTcF) ≥ 480 milliseconds. This criterion does not apply to patients with a right or left 
bundle branch block. 
17. History of unstable angina or ventricular arrhythmia requiring medication or mechanical 
control within 6 months before Screening. 
18. History of major thromboembolic event (eg, stroke, myocardial infarction, pulmonary 
embolism) ≤ 6 months before the first dose of study drug.  
• Exception: Patients with history of deep vein thrombosis are permitted if they are 
on stable anticoagulation treatment for at least 3 months before the first dose of 
study drug.  
19. Any gastrointestinal condition that would preclude the use of oral medications (eg, 
difficulty swallowing, nausea, vomiting, or malabsorption). 
20. Major surgery within 4 weeks before Screening. 
21. Ongoing, uncontrolled, systemic bacterial, fungal, or viral infections at Screening. Oral 
antibiotics for a controlled infection are permitted. Patients on antimicrobial, antifungal, 
or antiviral prophylaxis are not excluded if all other inclusion and exclusion criteria are 
met. No severe infection within 4 weeks before first dose. 


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22. Unstable or severe, uncontrolled medical condition, important medical illness, abnormal 
laboratory finding, or psychological condition, that would, in the Investigator’s 
judgment, increase the risk to the patient associated with participation in the trial or 
interfere with safe completion of the trial. 
Dosing: 
The doses of SRF617, etrumadenant, and zimberelimab are presented below and will be given 
on a 28-day cycle: 
Study drug 
Dose 
SRF617 
1400 mg intravenously (IV) every 2 weeks 
(q2 weeks) on Days 1 and 15 
Etrumadenant 
150 mg orally daily 
Zimberelimab 
480 mg IV every 4 weeks (q4 weeks) on 
Day 1 
Response Assessments 
Assessment of response will be evaluated by computed tomography or magnetic resonance 
imaging of chest/abdomen/pelvis and bone scan every 12 weeks. PSA will be performed every 
cycle. Patients should continue past PSA progression until clear radiologic progression or 
clinical progression. If osseous disease is present at Baseline, disease assessment will follow 
the 2+2 rule to discriminate between flare and true progressive disease in bone lesions. Patients 
will be permitted to continue on study drug past progression if the Investigator feels the patient 
is otherwise experiencing clinical benefit and Sponsor agrees. 
Statistical Methodology 
Sample Size Determination 
This trial will enroll approximately 40 patients. A patient is enrolled in the trial after they have 
provided informed consent and met all trial eligibility criteria.  
A Simon 2-stage design will be implemented. Simon Stage 1 will include a 6-patient Safety 
Lead-in followed by enrollment of an additional 11 patients for a total of 17 patients. At least 1 
radiographic CR/PR or 2 PSA50 responses by PCWG3 criteria out of 17 evaluable patients must 
be observed in order to consider opening Stage 2, which will enroll an additional 23 patients for 
further evaluation of the safety and efficacy of the triplet. The trial will have met its primary 
endpoint if at least 8 patients in total achieve a response. 
The sample size for this triplet combination therapy dose expansion is based on a null 
hypothesis of a 10% composite response rate (PSA50 or CR/PR) with PD-1 blockade alone 
versus the alternate hypothesis that the composite response rate is 30%, with a calculated alpha 
of 0.040 and power of 0.93. 


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Analysis Sets 
The Safety Lead-in Evaluable Analysis Set is defined as the first 6 patients enrolled in the 
Simon stage 1 who either experienced a Grade ≥ 3 related AE during the first cycle of therapy 
(D1-28) or who completed at least 50% of the prescribed combination therapy doses. The SRC 
will review the aggregate safety data of these 6 patients during Cycle 1 and must clear the trial 
for further enrollment of the remaining 11 patients in Stage 1. The goal of the safety evaluation 
for the triplet is to evaluate for any signal of unexpected or increased toxicities when given 
together that would not be observed with any agent alone. As such, a Grade ≥ 3 toxicity known 
to be associated with any of the 3 study drugs’ established safety profiles would not be 
considered concerning. 
The Safety Analysis Set is defined as all patients who received any amount of study drug. This 
analysis set will be the primary analysis set for all safety endpoints, excluding safety lead-in 
evaluation. This analysis set will be used to assess the tolerability of SRF617 in combination 
with etrumadenant and zimberelimab. 
The Response-Evaluable Analysis Set is defined as all patients at Baseline who received study 
drug and had at least 1 post-Baseline response assessment or who discontinued the treatment 
phase because of radiographic or symptomatic disease progression (including death caused by 
disease progression) within 6 weeks (+ 2 week window) of the first dose of study drug. This 
analysis set will be the primary analysis set for the primary efficacy endpoint and other efficacy 
endpoints. ORR will be assessed separately by PCWG3 criteria as well as RECIST v1.1. For 
the primary composite response endpoint of PSA50 or CR/PR, ORR will be measured using 
PCWG3 criteria. PSA response is defined as a confirmed PSA decrease from Baseline of 50% 
or more based on 2 consecutive assessments measured 3 to 4 weeks apart.1 Changes in PSA 
across the trial period will be described using a waterfall plot. Swimmer plots will be used to 
describe time on trial including timing and incidence of treatment past progression, timing of 
serious adverse events (SAEs) or adverse events of special interest (AESIs), and may be used to 
reflect the concept of no longer clinically benefiting.  
The Intent-to-Treat Analysis Set is defined as all enrolled patients who received any amount of 
study drug.  
Safety Analyses: 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 
22.0 or higher and will be graded according to NCI-CTCAE version 5.0 or higher.  
Summaries of AEs will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that 
emerges or worsens in the period from the first dose of study drug to 30 days after the last dose 
of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last dose of 
zimberelimab (30 days after the last dose of zimberelimab if the patient starts another 
anticancer therapy), whichever is later. 
TEAEs will be summarized by frequency and by MedDRA System Organ Class and Preferred 
Term. Separate tabulations will also be produced for TEAEs assessed as related to study 
drug(s), TEAEs leading to treatment discontinuation, TEAEs leading to death, AESIs, and 
TEAEs Grade ≥ 3 in severity. Treatment-emergent SAEs and SAEs related to study drug(s) will 
also be tabulated.  


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Shifts in grade (per NCI-CTCAE version 5.0 or higher) from Baseline to the maximum 
post-Baseline grade will be summarized for applicable laboratory data. Laboratory values 
Grade ≥ 3 in severity will be tabulated. 
Incidence of SSEs per PCWG3 criteria, defined as symptomatic fracture, radiation or surgery to 
bone, or spinal cord compression, will be reported.1  
 
 
 


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Table 1: 
Screening Assessments Checklist 
• 
Informed consenta 
• 
Inclusion/exclusion criteria 
• 
Medical history and demographics 
• 
Cancer history and Baseline disease 
characterizationb 
• 
Prior/concomitant medications and 
proceduresc 
• 
Full physical examinationd 
• 
ECOG performance status 
• 
ECG (12-lead)e (local read only) 
• 
Blood chemistryf 
• 
Hematologyf 
• 
Coagulationf 
• 
LDHf 
• 
LFTsf  
• 
Amylase and lipasef 
• 
TSH and FT4 testing 
• 
Urinalysisf 
• 
Hepatitis serology (HCV Ab, HBsAg)g 
• 
HIVh 
• 
Buccal swab for pharmacogenomics 
• 
PSA 
• 
PAP 
• 
Testosterone 
• 
Tumor evaluationi 
• 
AE/SAE assessmentj 
• 
Tumor biopsyk 
• 
Archival tumor tissuel 
Abbreviations: AE = adverse event; CT = computed tomography; ECG = electrocardiogram; ECOG = Eastern 
Cooperative Oncology Group; EoT = end of treatment; FT4 = free thyroxine; HBsAg = hepatitis B surface antigen; 
HCV Ab = hepatitis C antibody; HIV = human immunodeficiency virus; ICF = informed consent form; 
LDH = lactate dehydrogenase; LFT = liver function test; MRI = magnetic resonance imaging; PAP = prostatic acid 
phosphatase; PCWG3 = Prostate Cancer Working Group 3 criteria; PSA = prostate-specific antigen; 
RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; TSH = thyroid stimulating 
hormone  
Note: All Screening assessments will be performed ≤ 30 days before the first dose. See Section 6 for details on each 
trial assessment. 
a Informed consent must be obtained before performing Screening assessments (see Section 6.1.1). 
b Include documentation of all previous treatments and treatment results (ie, best response to previous disease-
specific treatments) (see Section 6.1.3). 
c Includes medications received and medical procedures performed within the previous 30 days (previous 6 weeks 
for live attenuated vaccines) and any cancer treatment procedures from any time in the past (see Section 6.1.4). 
d Full physical examination parameters described in Section 6.1.5. 
e A 12-lead ECG will be conducted at Screening after an approximately 10-minute rest period (see Section 6.1.7). 
Heart rate–corrected QT interval measurements will use Fridericia’s correction method. Subsequent ECGs may be 
performed if clinically indicated, per Investigator discretion. 
f For a list of all blood chemistry, LDH, LFTs, amylase, lipase, hematology, and coagulation parameters and 
urinalysis details, see Section 6.1.8. 
g All patients will be tested for anti-HCV Ab and HBsAg at Screening as described in Section 6.1.9. 
h Patients without documentation of a prior negative HIV test result (eg, antibody, antigen, or polymerase chain 
reaction-based test) are required to undergo HIV testing during Screening. Only patients with negative HIV results 
will be eligible to enroll.  
i Quantification of Baseline disease burden by PCWG3 criteria and RECIST v1.1 must be performed within 30 days 
before the first dose of study drug. Imaging should adequately capture all known anatomical sites of disease 
involvement and at a minimum must include chest, abdomen, and pelvis and bone scan. The modality (CT, MRI) 
chosen to evaluate each individual patient should be the same throughout the duration of the trial. See 
Section 6.1.10 for more information on the disease-specific imaging requirements to be conducted at Screening.  
j SAEs for all patients will be reported from the time of signing the ICF (Section 8.1); non-serious AEs will be 
reported from the time of first dose. Clinically significant medical conditions observed at Screening that do not 
meet criteria for an SAE should be recorded as part of the patient’s medical history.  


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k Fresh tumor biopsies are optional and will be performed in patients who consent to the procedure, who have 
non-bone metastases amenable to biopsy, and for whom the procedure is deemed safe. Biopsies in these patients 
will be performed at Screening and, if also done on therapy, any time after dosing during Cycle 2 or EoT, 
whichever visit comes first. A + 7-day window for scheduling is permitted for EoT biopsies. See Section 6.1.11 
for more details.  
l Request for collection of archival tumor tissue to be initiated at Screening including a copy of associated 
pathology report. Archival tumor tissue is required to be collected for all patients unless Sponsor approval is 
obtained. Newly obtained core or excisional biopsy of a tumor lesion not previously irradiated is preferred to 
archived tissue. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides. Note: If submitting 
unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date 
slides are cut (details pertaining to tumor tissue submission can be found in the Laboratory Manual). 
 


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Table 2: 
Schedule of Assessments: SRF617 + Etrumadenant + Zimberelimab Combination Therapy  
 
Cycle 1 
Cycle 2 and Cycle 3 
≥ Cycle 4 
End of 
Treatmenta 
Safety  
Follow-
upb 
(28 ± 2 days) 
(28 ± 2 days) 
(28 ± 2 days) 
D1 
D2 
D8 
± 1 
D15 
± 1 
D1 ± 1 
D15 ± 1 
D1 ± 1 
D15 ± 1 
≤ 7 d from 
treatment 
termination 
30 or 90 
(+ 7) d 
from last 
dose 
Concomitant medications and 
procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE/SAE assessmentc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Symptom-directed physical 
examinationd 
Xe 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG performance status 
Xe 
X 
X 
X 
X 
ADA assessmentf 
See Table 3  
Pharmacokineticsf 
Blood chemistry, LFTs, LDH, 
amylase, lipase, hematology, 
coagulationg 
Xe 
X 
X 
Xh 
Xh 
Xh 
Xg,h 
Xg,h 
X 
X 
TSH and FT4 
Xe,h,i 
 
 
 
Xi 
 
Xi 
 
X 
 
PSAj 
Xe,h 
Xh 
Xh 
X 
PAP 
Xe,h 
 
 
 
Xh 
 
Xh 
 
X 
 
Blood for PBMC 
immunophenotypingk 
X 
 
 
X 
X 
 
X 
 
X 
 
Blood for cytokine analysisl 
X 
 
 
X 
X 
 
X 
 
X 
 
Tumor biopsym 
Xm 
Xm 
SRF617 administrationn 
X 
X 
X 
X 
X 
X 


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Cycle 1 
Cycle 2 and Cycle 3 
≥ Cycle 4 
End of 
Treatmenta 
Safety  
Follow-
upb 
(28 ± 2 days) 
(28 ± 2 days) 
(28 ± 2 days) 
D1 
D2 
D8 
± 1 
D15 
± 1 
D1 ± 1 
D15 ± 1 
D1 ± 1 
D15 ± 1 
≤ 7 d from 
treatment 
termination 
30 or 90 
(+ 7) d 
from last 
dose 
Zimberelimab administrationn 
X 
 
 
 
X 
 
X 
 
 
 
Etrumadenant administrationn 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Etrumadenant treatment 
compliance assessmentn 
X 
 
 
X 
X 
X 
X 
 
X 
 
Disease response assessmentso 
 
 
 
 
Response assessment every 12 wks (± 7 days) after 
C1D1 dosing 
X 
 
Abbreviations: ADA = antidrug antibody; AE = adverse event; aPTT = activated partial thromboplastin time; CXDX = Cycle X Day X; d = day; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EoT = end of treatment; FT4 = free thyroxine; ICF = informed consent form; 
INR = international normalized ratio; LDH = lactate dehydrogenase; LFT = liver function test; PBMC = peripheral blood mononuclear cell; 
PK = pharmacokinetic(s); PAP = prostatic acid phosphatase; PSA = prostate-specific antigen; PT = prothrombin time; SAE = serious adverse event; 
TSH = thyroid stimulating hormone 
a The EoT visit should occur for any patient when they discontinue the last study drug. Each assessment need not be performed if the patient had an identical 
assessment within the previous 2 weeks. Disease response assessment is not required for patients whose most recent scan was ≤ 6 weeks before EoT visit. 
b All patients will have a Safety Follow-up visit approximately 30 days after the last dose of SRF617, 30 days after the last dose of etrumadenant, or 90 days 
(+ 7 days) after the last dose of zimberelimab (30 days after the last dose of zimberelimab if the patient initiates a new anticancer therapy), whichever is later. If 
possible, this visit should occur before the initiation of any subsequent anticancer therapy. At minimum, this visit should include collection of AEs/SAEs and 
concomitant medications/procedures. This can be performed by telephone call if the patient does not require laboratory and/or other procedures related to any 
new or ongoing AEs, in which case, a clinic visit will be required. 
c SAEs for all patients will be reported from the time of signing the ICF through 30 days after the last dose of SRF617, 30 days after the last dose of 
etrumadenant, or 90 days after the last dose of zimberelimab (30 days after the last dose of zimberelimab if the patient initiates new anticancer therapy), 
whichever is later (Section 8.1). Nonserious AEs are collected and monitored from the time of first dose through 30 days after the last dose of SRF617, 30 days 
after the last dose of etrumadenant, or 90 days after the last dose of zimberelimab (30 days after the last dose of zimberelimab if the patient starts another 
anticancer therapy), whichever is later. Clinically significant medical conditions observed at Screening that do not meet criteria for an SAE should be recorded 
as part of the patient’s medical history. Pregnancies occurring in partners of male patients are considered immediately reportable events if the pregnancy occurs 
during the study treatment period through 30 days after the patient’s last dose of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last 
dose of zimberelimab, whichever is later.  
d Physical examination will include an evaluation of disease-relevant systems and capture of vital signs. See Section 6.1.5 for more details. 
e The following Screening evaluations performed within 7 days of the first dose (C1D1) can be used to meet C1D1 criteria and do not need to be repeated: 
physical examination, ECOG performance status, coagulation parameters, TSH, FT4, PSA, PAP, LDH, amylase, and lipase. 


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f An additional blood sample for SRF617 PK and ADA should be drawn if a patient presents with a toxicity that meets the safety stopping rules, including such a 
toxicity outside of Cycle 1. See Section 4.6 and Section 6.1.12 for more details. 
g Blood chemistry, LFTs, and hematology will be performed at every trial visit prior to dosing. On C1D2, sample collection should occur 24 (± 2) hours post 
infusion of the last administered study drug. On each D1 and D15 infusion visit, sample should be collected within 48 hours before dosing of SRF617/the first 
infusion study drug. LDH, amylase, and lipase will be collected within 48 hours before dosing of SRF617/the first infusion study drug on D1of each cycle. 
Additional (unscheduled) assessments should be performed as clinically indicated. After Cycle 5, only hematology and blood chemistry including LFTs and 
LDH will be performed. Coagulation parameters will be assessed only at Screening and C1D1 and then as needed. If patient is on anticoagulation that affects 
PT/INR or aPTT, the appropriate parameter(s) should be measured on D1 of each cycle prior to dosing. See Section 6.1.8 for detailed parameters. 
h Sample collection should be completed within 48 hours before dosing of SRF617/the first infusion study drug. 
i TSH and FT4 should be collected within 48 hours of D1 of every other cycle after C1D1 (eg, C3D1, C5D1, C7D1, etc). If TSH and/or FT4 result(s) are outside 
of the normal range, test(s) should be repeated, treatment should be initiated if appropriate, and results recorded at each visit until they are back to Baseline. 
j The Investigator should follow PSA every cycle. If it is standard of care to follow a biomarker at a frequency other than once per cycle, Investigator should 
follow standard of care. 
k PBMC samples will be collected within 24 (+2) hours before dosing of SRF617 at C1D1, C1D15, C2D1, C3D1, C4D1, C7D1, and EoT.  
l Blood samples for analysis of cytokines, chemokines, and other soluble factors collected at C1D1 and C3D1 should be collected before dosing of SRF617, and 
6 hours ± 15 minutes post SRF617 infusion. C1D15 and all other samples on D1 of a cycle should be collected before dosing of SRF617. EoT samples may be 
collected at any time during the visit.  
m Fresh tumor biopsies are optional and will be performed in patients who consent to the procedure, who have non-bone metastases amenable to biopsy, and for 
whom the procedure is deemed safe. Biopsies in these patients will be performed at Screening and, if also done on therapy, any time after dosing during 
Cycle 2 or EoT, whichever visit comes first. A + 7-day window for scheduling is permitted for EoT biopsies. See Section 6.1.11 for more details. 
n Patients will receive SRF617 once every 2 weeks on Days 1 and 15 of each cycle and zimberelimab once every 4 weeks on Day 1 of each cycle until 
documented disease progression or unacceptable toxicity through Cycle 24. Patients will take etrumadenant orally once daily. On Day 1 and Day 15 infusion 
visit days, patients should hold etrumadenant administration until directed by trial personnel (see Section 7 for more details). On all other days, patients may 
take etrumadenant at home. To assess compliance with self-administration of etrumadenant, patients will be required to record the time and date they took each 
dose in a drug diary; missed doses will also be recorded. Patients will be instructed to bring all unused doses of etrumadenant and their drug diary to the clinic 
at specified visits for assessments of compliance. Patients may remain on study treatment longer than 2 years with agreement from the trial Investigator and 
Sponsor.  
o To include imaging consistent with anatomic areas and modality used at Screening and response evaluation by Investigator (see Section 6.3). These evaluations 
will be conducted on treatment or after treatment discontinuation until the patient experiences progressive disease or discontinues the trial. 


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Table 3: 
Schedule of Pharmacokinetic and Antidrug Antibody Assessments for Combination Therapy  
Cycle 
Day 
Scheduled time point 
SRF617 PK 
samplea 
Etrumadenant 
PK sample 
Zimberelimab 
PK sample 
SRF617 ADA 
samplea 
Zimberelimab 
ADA sample 
1 
1 
Predoseb,c 
X 
X 
X 
X 
X 
Immediately post SRF617 infusion 
(+ 30 min) 
X 
 
 
 
 
15 (± 1) 
Predoseb,c 
X 
X 
 
 
 
 
Immediately post SRF617 infusion 
(+ 30 min) 
X 
 
 
 
 
2 
1 (± 1) 
Predoseb,c 
X 
X 
X 
X 
X 
Immediately post SRF617 infusion 
(+ 30 min) 
X 
 
 
 
15 (± 1) 
Predose,c 
X 
 
 
 
Immediately post SRF617 infusion 
(+ 30 min) 
X 
 
 
 
3 
1 (± 1) 
Predoseb,c 
X 
X 
X 
X 
 
Immediately post SRF617 infusion 
(+ 30 min) 
X 
 
 
 
15 (± 1) 
Predoseb,c 
X 
 
 
 
 
 
Immediately post SRF617 infusion 
(+ 30 min) 
X 
 
 
 
 
4 and 
beyondd 
1 (± 1) 
Predoseb,c 
X 
X 
X 
X 
X 
Immediately post SRF617 infusion 
(+ 30 min) 
X 
 
 
 
EoT 
-- 
-- 
X 
X 
X 
X 
X 
Abbreviations: ADA = antidrug antibody; EoT = end of treatment; PK = pharmacokinetics 
a 
An additional blood sample for SRF617 PK and ADA should be drawn if a patient presents with a toxicity that meets the safety stopping rules, including 
such a toxicity outside of Cycle 1. See Section 4.6 and Section 6.1.12 for more details. 


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b 
On infusion visit days (Day 1 and Day 15 of each cycle), patients will hold etrumadenant administration until directed by trial personnel. Predose PK and 
ADA samples collected on these days should be collected before dosing of any study drugs. On all other days, patients may take etrumadenant at home. 
c 
Pre-dose PK samples obtained on Cycle 1 Day 1 may be collected within 24 hours before SRF617 dosing. Predose PK samples obtained after Cycle 1 Day 1 
may be collected within 2 hours before SRF617 dosing. 
d 
Beginning with Cycle 4, SRF617 PK and ADA samples will be collected on Day 1 of each cycle and EoT. Etrumadenant and zimberelimab PK samples and 
zimberelimab ADA samples will only be collected on Cycle 4 Day 1, Cycle 8 Day 1, Cycle 13 Day 1, and EoT. 


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TABLE OF CONTENTS 
INVESTIGATOR PROTOCOL APPROVAL ................................................................................2 
SPONSOR PROTOCOL APPROVAL ...........................................................................................3 
CONTACT INFORMATION ..........................................................................................................4 
PROTOCOL SYNOPSIS.................................................................................................................5 
TABLE OF CONTENTS ...............................................................................................................22 
LIST OF TABLES .........................................................................................................................26 
LIST OF FIGURES .......................................................................................................................27 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................28 
1. 
BACKGROUND ........................................................................................................31 
1.1. 
Castration-Resistant Prostate Cancer ..........................................................................31 
1.2. 
Adenosine Pathway in Cancer ....................................................................................32 
1.3. 
CD39 ...........................................................................................................................34 
1.3.1. 
CD39 and Prostate Cancer ..........................................................................................34 
1.4. 
SRF617 .......................................................................................................................35 
1.4.1. 
Summary of Nonclinical Safety of SRF617 ...............................................................35 
1.4.2. 
Rationale to Combine SRF617 With PD-1 Blockade .................................................36 
1.4.3. 
Summary of Clinical Studies of SRF617 ....................................................................37 
1.5. 
Etrumadenant (AB928) ...............................................................................................37 
1.6. 
Zimberelimab (AB122) ..............................................................................................38 
1.7. 
Rationale for Combining Etrumadenant and Zimberelimab ......................................39 
1.8. 
Trial Rationale ............................................................................................................39 
1.8.1. 
Selection of Patient Populations .................................................................................40 
1.9. 
Determination of Dose and Schedule .........................................................................40 
2. 
OBJECTIVES .............................................................................................................42 
2.1. 
Primary Objectives .....................................................................................................42 
2.2. 
Secondary Objectives .................................................................................................42 
2.3. 
Exploratory Objectives ...............................................................................................42 
3. 
ENDPOINTS ..............................................................................................................43 
3.1. 
Primary Endpoints ......................................................................................................43 
3.2. 
Secondary Endpoints ..................................................................................................43 
3.3. 
Exploratory Endpoints ................................................................................................43 


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4. 
TRIAL DESIGN .........................................................................................................44 
4.1. 
Stage 1 ........................................................................................................................44 
4.2. 
Stage 2 ........................................................................................................................44 
4.3. 
Safety Review Committee ..........................................................................................44 
4.4. 
Dosing Frequency .......................................................................................................45 
4.5. 
Monitoring of Adverse Events ....................................................................................45 
4.6. 
Trial Stopping Rules ...................................................................................................45 
4.7. 
Treatment Discontinuation .........................................................................................46 
4.8. 
Trial Withdrawal .........................................................................................................47 
5. 
TRIAL POPULATION ..............................................................................................48 
5.1. 
Inclusion Criteria ........................................................................................................48 
5.2. 
Exclusion Criteria .......................................................................................................49 
6. 
TRIAL PROCEDURES AND ASSESSMENTS .......................................................52 
6.1. 
Procedures and Assessments ......................................................................................52 
6.1.1. 
Informed Consent .......................................................................................................52 
6.1.2. 
Inclusion and Exclusion Criteria ................................................................................52 
6.1.3. 
Medical History, Demographics, Disease Characterization, and Cancer 
History ........................................................................................................................52 
6.1.4. 
Prior/Concomitant Medications and Procedures ........................................................52 
6.1.5. 
Physical Examination .................................................................................................53 
6.1.6. 
Eastern Cooperative Oncology Group Performance Status ........................................53 
6.1.7. 
Electrocardiogram .......................................................................................................53 
6.1.8. 
Clinical Laboratory Tests ...........................................................................................53 
6.1.9. 
Additional Screening Laboratory Measurements .......................................................54 
6.1.10. 
Tumor Evaluation .......................................................................................................54 
6.1.11. 
Tumor Biopsies ...........................................................................................................55 
6.1.12. 
Pharmacokinetic Sampling .........................................................................................55 
6.1.13. 
Biomarker Assessments ..............................................................................................55 
6.2. 
Safety Assessments .....................................................................................................56 
6.2.1. 
Adverse Events ...........................................................................................................56 
6.2.2. 
Antidrug Antibody Assay ...........................................................................................57 
6.3. 
Response Assessment Procedures ..............................................................................57 
6.3.1. 
Response Evaluation Criteria .....................................................................................57 


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6.4. 
Safety Follow-up Visit ................................................................................................58 
6.5. 
Long-term Follow-up for Safety .................................................................................58 
6.6. 
Concomitant Medications or Procedures ....................................................................58 
6.6.1. 
Transfusion Support (Prophylaxis or Supportive Care) .............................................58 
6.6.2. 
Prohibited Medications ...............................................................................................58 
6.6.3. 
Other Concomitant Therapies or Procedures ..............................................................59 
6.6.4. 
Contraception and Pregnancy .....................................................................................60 
7. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................62 
7.1. 
SRF617 .......................................................................................................................62 
7.1.1. 
Description of SRF617 ...............................................................................................62 
7.1.2. 
SRF617 Dosage ..........................................................................................................62 
7.1.3. 
SRF617 Administration ..............................................................................................62 
7.1.4. 
SRF617 Storage ..........................................................................................................63 
7.1.5. 
SRF617 Preinfusion Medications ...............................................................................63 
7.1.6. 
SRF617 Postinfusion Medications .............................................................................64 
7.1.7. 
SRF617 Treatment Continuation ................................................................................64 
7.2. 
Etrumadenant ..............................................................................................................64 
7.2.1. 
Etrumadenant Dosage .................................................................................................64 
7.2.2. 
Etrumadenant Administration .....................................................................................64 
7.3. 
Zimberelimab ..............................................................................................................65 
7.3.1. 
Zimberelimab Dosage .................................................................................................65 
7.3.2. 
Zimberelimab Administration ....................................................................................65 
7.4. 
Dose Holds, Modifications, and Discontinuations .....................................................65 
7.5. 
Drug Accountability ...................................................................................................76 
7.6. 
Assignment to Treatment ............................................................................................76 
8. 
SAFETY DATA COLLECTION, RECORDING, AND REPORTING ....................77 
8.1. 
Adverse Events ...........................................................................................................77 
8.1.1. 
Definition of an Adverse Event ..................................................................................77 
8.1.2. 
Definition of Serious Adverse Event ..........................................................................77 
8.1.3. 
Definition of an Adverse Event of Special Interest ....................................................78 
8.2. 
Procedures for Recording and Reporting Adverse Events .........................................78 
8.2.1. 
Recording Adverse Events .........................................................................................78 
8.2.2. 
Reporting of Serious Adverse Events and Adverse Events of Special Interest ..........80 


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8.2.3. 
Pregnancy and In Utero Drug Exposure .....................................................................81 
9. 
STATISTICAL METHODS .......................................................................................83 
9.1. 
Sample Size ................................................................................................................83 
9.2. 
Analysis Sets ...............................................................................................................83 
9.2.1. 
Safety Lead-in Evaluable Analysis Set .......................................................................83 
9.2.2. 
Safety Analysis Set .....................................................................................................83 
9.2.3. 
Response-Evaluable Analysis Set ...............................................................................83 
9.2.4. 
Intent-to-Treat Analysis Set ........................................................................................84 
9.2.5. 
SRF617 Pharmacokinetics Analysis Set .....................................................................84 
9.2.6. 
Biomarker Analysis Set ..............................................................................................84 
9.2.7. 
Tumor Biopsy Analysis Set ........................................................................................84 
9.3. 
Background Characteristics ........................................................................................84 
9.3.1. 
Patient Disposition ......................................................................................................84 
9.3.2. 
Demographics and Baseline Characteristics ...............................................................84 
9.4. 
Study Drug Exposure and Compliance .......................................................................84 
9.5. 
Efficacy Analyses .......................................................................................................85 
9.6. 
Safety Analyses ..........................................................................................................86 
9.6.1. 
Adverse Events ...........................................................................................................86 
9.6.2. 
Clinical Laboratory Assessments ...............................................................................86 
9.7. 
Pharmacokinetic Analyses ..........................................................................................86 
9.8. 
Biomarker Analyses ....................................................................................................87 
10. 
TRIAL ADMINISTRATION .....................................................................................88 
10.1. 
Good Clinical Practice Statement ...............................................................................88 
10.2. 
Informed Consent .......................................................................................................88 
10.3. 
Patient Confidentiality ................................................................................................88 
10.4. 
Institutional Review Board/Ethics Committee Requirements ....................................89 
10.5. 
Case Report Forms and Source Documentation .........................................................89 
10.6. 
Sponsor Monitoring ....................................................................................................89 
10.7. 
Data Monitoring Committee .......................................................................................89 
10.8. 
Quality Assurance .......................................................................................................90 
10.9. 
Trial or Clinical Site Termination ...............................................................................90 
10.10. 
Duration of the Trial, Expected Duration of Patient Participation, and End of 
Trial .............................................................................................................................90 


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10.11. 
Records Retention .......................................................................................................90 
10.12. 
Publications .................................................................................................................90 
11. 
REFERENCES ...........................................................................................................91 
APPENDIX 1. LIST OF PROHIBITED OR CAUTIONARY MEDICATIONS FOR 
CONCOMITANT USE WITH ETRUMADENANT ................................................98 
APPENDIX 2. EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE 
STATUS ...................................................................................................................102 
APPENDIX 3. RESPONSE CRITERIA ...................................................................................103 
 
LIST OF TABLES 
Table 1: 
Screening Assessments Checklist ...............................................................................15 
Table 2: 
Schedule of Assessments: SRF617 + Etrumadenant + Zimberelimab 
Combination Therapy .................................................................................................17 
Table 3: 
Schedule of Pharmacokinetic and Antidrug Antibody Assessments for 
Combination Therapy .................................................................................................20 
Table 4: 
Stopping Rule Exceptions ...........................................................................................45 
Table 5: 
Timing of Administration of Study Drug on Infusion Days in Trial 
SRF617-201 ................................................................................................................63 
Table 6: 
Hematologic Toxicities Leading to Dose Hold of SRF617 ........................................66 
Table 7: 
Nonhematologic Toxicities Leading to Dose Hold, Modification, or 
Discontinuation of SRF617 ........................................................................................68 
Table 8: 
Recommended Dose Reductions for SRF617 ............................................................69 
Table 9: 
Recommended Dose Reductions for Etrumadenant ...................................................70 
Table 10: Guidelines for Management of Patients who Experience Adverse Events 
Considered to be Related to Etrumadenant and/or Zimberelimab ..............................71 
Table 11: List of Prohibited or Cautionary Medications for Concomitant Use With 
Etrumadenant ..............................................................................................................98 
Table 12: PCWG3 Baseline Assessment of Disease – Amended for Trial SRF617-201 .........103 
Table 13: PWCG3 Criteria for Progression at Trial Entry .......................................................105 
Table 14: RECIST Version 1.1 Lesion Response .....................................................................107 
Table 15: Evaluation of Overall Response by RECIST Version 1.1 ........................................108 
 
 


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LIST OF FIGURES 
Figure 1: 
The adenosine pathway’s role in antitumor immunity ...............................................33 
Figure 2: 
CD39 exhibits a stromal expression pattern in prostate cancer ..................................35 
Figure 3: 
An antimurine-CD39 surrogate antibody in combination with an antimurine 
PD-1 antibody increases survival in a syngeneic CT26 tumor model ........................37 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ADA 
antidrug antibody 
ADL 
activities of daily living 
ADP 
adenosine diphosphate 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AMP 
adenosine monophosphate 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ARSI 
androgen receptor signaling inhibitor 
AST 
aspartate aminotransferase 
ATP 
adenosine triphosphate 
BCRP 
breast cancer resistance protein 
C1D1 
Cycle 1 Day 1 
CNS 
central nervous system 
CR  
complete response 
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
DCR 
disease control rate 
DoR 
duration of response 
DVT 
deep vein thrombosis 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ENTPD1 
ectonucleoside triphosphate diphosphohydrolase-1 
EoT 
end of treatment 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GLP 
Good Laboratory Practice 
HBcAb 
hepatitis B core antibody 


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HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HCV Ab 
hepatitis C virus antibody 
HR 
hazard ratio 
HSPC 
hormone-sensitive prostate cancer 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
independent ethics committee 
IFN 
interferon 
IgG4 
immunoglobulin G4 
IL 
interleukin 
INR 
international normalized ratio 
IRB 
institutional review board 
IV 
intravenous(ly) 
KO 
knockout 
LDH 
lactate dehydrogenase 
mCRPC 
metastatic castration-resistant prostate cancer 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NECA 
5′-N-ethylcarboxamide adenosine 
NK 
natural killer 
ORR 
objective response rate 
OS 
overall survival 
PAP 
prostatic acid phosphatase 
PBMC 
peripheral blood mononuclear cell 
pCREB 
cAMP response element-binding protein  
PCWG3 
Prostate Cancer Working Group 3  
PD-1 
programmed death receptor-1 
PD-L1/2 
programmed death-ligand 1/2 
PFS 
progression free survival 
PK 
pharmacokinetic(s) 


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PR 
partial response/remission 
PSA 
prostate-specific antigen 
PSA30 
PSA decline ≥ 30% 
PSA50 
PSA decline ≥ 50%  
PT 
prothrombin time 
q2 weeks 
once every 2 weeks 
q4 weeks 
once every 4 weeks 
QTc 
heart rate–corrected QT interval 
QTcF 
QT interval corrected with Fridericia’s method 
RBC 
red blood cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SRC 
Safety Review Committee 
SSE 
symptomatic skeletal events 
TEAE 
treatment-emergent adverse event 
TME 
tumor microenvironment 
TNFα 
tumor necrosis factor alpha 
ULN 
upper limit of normal 
 


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1. 
BACKGROUND 
1.1. 
Castration-Resistant Prostate Cancer 
Prostate cancer is the second most common cancer in incidence and the fifth leading cause of 
death in men worldwide.2 It is estimated that approximately 249,000 new cases will be diagnosed 
in the United States in 2021, with approximately 34,000 related deaths due to metastatic disease.3 
Current approaches to the treatment of hormone-sensitive metastatic prostate cancer have 
changed rapidly in the last several years, with significant survival advantages achieved by adding 
docetaxel chemotherapy4, 5 or novel androgen receptor signaling inhibitors ([ARSIs] eg, 
abiraterone, enzalutamide, apalutamide6-9) to standard androgen deprivation therapy upon a 
backbone of gonadotropin-releasing hormone analogs in patients who have not had bilateral 
orchiectomy. However, almost all patients will still transition to castration-resistant prostate 
cancer (CRPC, progression despite testosterone levels < 50 ng/dL) in approximately 15 to 19 
months5, 10, which is responsible for most of the morbidity and the mortality of prostate cancer. 
While the advances in the hormone-sensitive space have translated to significant increases in 
overall survival (OS), they have created challenges as to the optimal sequencing of subsequent 
treatments for CRPC. Most patients will receive several second-line regimens for metastatic 
CRPC (mCRPC) ranging from taxane chemotherapy (docetaxel, cabazitaxel11, 12), alternative 
ARSIs (eg, enzalutamide or abiraterone), or the dendritic cell vaccine sipuleucel-T.13 Selected 
patients may receive radium-223, if disease is predominantly represented by bone metastases14, 
or PARP inhibitors (eg, olaparib, rucaparib) for tumors that contain certain DNA repair pathway 
mutations or alterations.15, 16 However, prospective studies and retrospective analyses have 
shown that sequencing one ARSI after another or layering on an additional ARSI achieves 
disappointingly short times to disease progression (by prostate-specific antigen [PSA] or 
radiologically) on the order of 3 to 6 months, especially if the patient has already received both a 
taxane and an ARSI.17-24 The randomized Phase 2 CARD trial (n = 225) investigated whether 
patients whose disease had had prior docetaxel exposure (minimum 3 cycles) and who had 
progressed within the past 12 months on an ARSI with enzalutamide or abiraterone would have a 
longer progression-free survival (PFS) and OS if given cabazitaxel next rather than switching to 
the other ARSI.25 Receipt of cabazitaxel doubled the imaging-based median PFS (8.0 vs. 3.7 
months, hazard ratio [HR] 0.54, p < 0.001) and significantly improved the median OS (13.6 vs 
11 months, HR 0.64, p = 0.008) over receiving the alternative ARSI.  
Prostate cancer is generally an immunologically cold tumor. Attempts at leveraging immune 
checkpoint inhibition with programmed death receptor-1 (PD-1) or cytotoxic T-lymphocyte-
associated protein 4 (CTLA-4) blockade, which have provided significant clinical benefit across 
other solid tumors, have been less fruitful in mCRPC, with an objective response rate (ORR) of 
< 15%.26-29 Multiple Phase 3 trials are ongoing to evaluate PD-1 blockade with standard 
therapies such as docetaxel or enzalutamide. Two Phase 3 trials of the anti-CTLA-4 antibody 
ipilimumab did not induce a survival benefit in either the pre- or post-chemotherapy mCRPC 
space.30-32 As such, immune checkpoint blockade in the form of anti-PD-1 is only approved for 
selected prostate cancers in which there is mismatch repair deficiency (eg, MLH1, MSH2, 
MSH6, PMS2) or high tumor mutational burden.28 
Despite these advances and a multitude of drugs now approved for mCRPC, it remains uniformly 
fatal due to inherent or adaptive resistance mechanisms, and more effective therapies are needed. 


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One such resistance pathway in prostate cancer may be the adenosine pathway. The tumor 
microenvironment (TME) contains high levels of adenosine, an immunosuppressive chemical 
which binds to and activates the A2a and A2b receptors on immune cells resulting in a dampened 
immune response against the tumor. Extracellular adenosine is primarily produced by the 
enzyme CD73. In prostate cancer, A2bR is upregulated33-35 and the activity of prostatic acid 
phosphatase (PAP) produces additional adenosine36, 37, suggesting this tumor type may be more 
susceptible than others to adenosine-mediated immunosuppression. 
1.2. 
Adenosine Pathway in Cancer 
The purine nucleoside adenosine has a critical role in dampening innate and adaptive immune 
responses under various inflammatory conditions.38 In contrast, high levels of extracellular 
adenosine triphosphate (ATP) generated as a result of tissue damage or immunogenic cell death 
can initiate pro-inflammatory responses.39 Extracellular adenosine accumulates in cancerous 
tissues through the degradation of ATP and constitutes an important mechanism of tumor 
immune escape, induction of angiogenesis, and metastasis.40 Early studies demonstrated that 
adenosine could inhibit CD3+ T-cell and natural killer (NK) cell function, and endogenous 
adenosine levels in tumors would be sufficient to mediate immunosuppression.41 Other studies 
have shown that high levels of ATP can act as a potent chemoattractant for innate immune cells 
and can mediate robust inflammation leading to activation of adaptive immune responses.39 
Thus, there is an important role for both extracellular adenosine and ATP in cancer maintenance 
and progression. Thus, inhibition of extracellular adenosine while maintaining high levels of 
ATP in the TME may have anticancer therapeutic activity. 
Reduction of ATP and subsequent increase of extracellular adenosine production in the TME 
depends on the concerted enzymatic activity of 2 ectonucleotidases, CD73 (5'-nucleotidase ecto) 
and CD39 (ectonucleoside triphosphate diphosphohydrolase-1 [ENTPD1]). CD39 catalyzes the 
hydrolysis of ATP and adenosine diphosphate (ADP) to adenosine monophosphate (AMP) and 
CD73 hydrolyzes AMP to adenosine (Figure 1). The effects of adenosine are mediated via 
interactions with adenosine-binding G-protein coupled receptors (A1, A2A, A2B, and A3). 
Notably, adenosine inhibits the activation and expansion of T cells primarily via the A2A 
receptor. Mice that lack the A2A receptor have reduced tumor growth as compared with their 
wildtype littermates, providing genetic evidence for the adenosine/A2A receptor pathway in 
protecting tumors from antitumor T cells.42 A2A receptor stimulation also upregulates expression 
of coinhibitory molecules such as CTLA-4 and PD-143, while stimulation of A2bR results in 
adenosine-driven suppression of myeloid cells through the A2bR present on dendritic cells and 
macrophages. 


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Figure 1: 
The adenosine pathway’s role in antitumor immunity 
 
Abbreviations: AMP = adenosine monophosphate; ATP = adenosine triphosphate; NK = natural killer; 
TME = tumor microenvironment 
CD39 is a key enzyme modulating innate and adaptive immune responses. Extracellular adenosine suppresses tumor 
immunity, while extracellular ATP stimulates innate immunity. Antibody blockade of CD39 decreases AMP and 
adenosine and increases ATP in the TME. 
Studies examining reduction of adenosine through inhibition or loss of CD73 have further 
validated this pathway in mediating tumor immune evasion. Host CD73 deficiency or 
neutralizing antibodies targeting CD73 lead to delayed tumor growth in multiple syngeneic 
transplantable tumor models, including ovalbumin-expressing MC38 colon cancer, EG7 
lymphoma, AT-3 mammary tumors, ID8 ovarian tumors, B16F10 melanoma, and TRAMP-C1 
prostate tumors.44 Depending on the model, the tumor-protective effects of CD73 blockade were 
dependent on CD8+ T cells, NK cells, and interferon gamma secretion.44 Targeting CD73 also 
enhances the activity of anti–PD-1 and anti–CTLA-4 antibodies in mouse syngeneic tumor 
models.45, 46 
Inhibition or loss of CD39 has been shown to have antitumor effects in multiple studies. Notably, 
in CD39 knockout (KO) mice, growth of both MC38 colon cancer cells and B16 melanoma 
hepatic metastatic tumors was significantly inhibited compared with growth in wild-type mice.47 
Interestingly, hepatic metastatic growth was also reduced in chimeric mice reconstituted with 
CD39−/− bone marrow–derived cells, suggesting that CD39 on immune cells alone contributes to 
tumor growth. In a complementary study, CD39 transgenic mice over-expressing CD39 were 
shown to have larger, more rapidly growing metastatic tumors after injection of CT26 colorectal 
cells.48 Treatment with the CD39 inhibitor sodium polyoxotungstate or an anti-CD39 antibody 
was also shown to limit metastatic tumor growth, 49, 50 and direct inhibition of CD39 has been 
shown to inhibit tumor angiogenesis in a variety of models. 47, 49-52 Taken together, these 
observations demonstrate the potential for targeting CD39 in cancer treatment and serve to 
further validate the importance of the extracellular adenosinergic pathway in promoting tumor 
growth. 


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1.3. 
CD39 
CD39 is an enzyme critical to both the production of adenosine and the breakdown of ATP. The 
accumulation of adenosine leads to immunosuppression, whereas maintained levels of ATP 
increase T-cell proliferation, dendritic cell maturation, and pro-inflammatory cytokine levels. 
The adenosine axis is a well-validated immune suppression pathway. CD39 is a key upstream 
target in the pathway modulating innate and adaptive immune responses. CD39 inhibition 
decreases immunosuppressive adenosine while stimulating innate immunity by potentiating ATP 
levels in the TME. Extracellular adenosine suppresses tumor immunity; extracellular ATP 
stimulates innate immunity.  
1.3.1. 
CD39 and Prostate Cancer 
Internal studies have revealed that prostate cancer can strongly express CD39 in the stromal 
compartment of tumors (Figure 2). In general, the TME of prostate cancer is largely devoid of 
immune infiltrate displaying a “cold” tumor phenotype.53 CD39 in the stroma of cancer tissue 
likely contributes to the immunosuppressive barrier by degrading extracellular ATP, thereby 
increasing adenosine levels. Inhibiting CD39 activity in the TME could increase ATP levels and 
reduce available adenosine, which in turn could induce antitumor inflammation of this 
immunologically “cold” tissue with resultant recruitment of immune cells, and ultimately 
suppression of tumor growth. 
PAP is a secreted glycoprotein enzyme that is widely present in prostate gland epithelial cells. 
While PSA is the universally tested serum biomarker for diagnosis and response assessment in 
prostate cancer management, serum PAP levels are also increased in patients with prostate 
cancer, and it was widely used as a biomarker prior to PSA testing. High PAP levels can 
correlate with earlier metastases, larger tumor size, higher pathological grade, and shortened 
survival.54, 55 Although PAP is expressed in other tissues such as brain, kidney, and placenta, its 
expression in normal prostate and prostate cancer tissues is 50-5000x and 110-6000x higher, 
respectively.56 Since more than 95% of prostate cancer cells express PAP, it has been used as a 
target antigen for prostate cancer immunotherapy.56 Although the exact physiological function of 
PAP is not clear, PAP can function as an ectonucleotidase and convert AMP to adenosine.54, 55 
Together with CD39, PAP may contribute to an adenosine-rich, immunosuppressive TME in 
prostate cancer. A recent trial has shown that serum PAP levels can be a useful indicator of an 
adenosine-rich TME.57 This is particularly important in this trial since both SRF617 and 
etrumadenant are therapeutics designed to decrease the immunosuppressive effect of adenosine 
in TME.  
 


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Figure 2: 
CD39 exhibits a stromal expression pattern in prostate cancer 
 
Abbreviations: IHC = immunohistochemistry, TME = tumor microenvironment 
Representative image of a human prostate cancer tissue sample demonstrating CD39 protein expression (brown 
staining) in the stromal component (blue arrow) of the TME by IHC. 
1.4. 
SRF617 
SRF617 is a fully human immunoglobulin G4 (IgG4) antibody against human ENTPD1, also 
known as CD39, that prevents CD39-mediated conversion of ATP and ADP to AMP and 
phosphate, leading to a reduction in adenosine levels within the TME. There is an important role 
for extracellular ATP and adenosine in cancer maintenance and progression. Maintaining high 
levels of ATP (and resultant low levels of adenosine) in the TME may have anticancer 
therapeutic activity.  
The ability of SRF617 to inhibit CD39 enzymatic activity was demonstrated in vitro with 
recombinant CD39 protein and on multiple cell types expressing both human and cynomolgus 
monkey CD39. Functional cellular immunologic assays demonstrated that SRF617 enhances 
T-cell proliferation and dendritic cell maturation in vitro. In vivo, SRF617 has shown significant 
antitumor activity after repeated dosing as a single agent in the MOLP-8 xenograft model in 
mice, which expresses high levels of CD39.  
1.4.1. 
Summary of Nonclinical Safety of SRF617  
The nonclinical toxicology program conducted in support of clinical trials for SRF617 consisted 
of 2 in vivo repeated-dose intravenous (IV) injection studies in cynomolgus monkeys, an in vitro 
cytokine release study using human peripheral blood mononuclear cells (peripheral blood 
mononuclear cells [PBMCs]), and an in vitro off-target binding study using human HEK293 
cells. The in vivo toxicology studies of SRF617 were conducted in cynomolgus monkeys, which 
was the only species identified as pharmacologically relevant based on SRF617 avidity for 
CD39. Both in vivo toxicology studies were conducted by the IV route of administration, which 
is the current clinical route of administration. The pivotal toxicology study was conducted in 
accordance with Good Laboratory Practice (GLP) regulations.  


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The weight of evidence from all the pharmacology and toxicology studies conducted with 
SRF617 in vitro and in vivo supports its safety in the treatment of patients with advanced cancer. 
All the in vivo safety studies conducted with SRF617 resulted in no significant findings up to 
100 mg/kg, corresponding to an average maximum serum concentration of 4,950,000 ng/mL and 
area under the curve of 91,400,000 h*ng/mL. Biologic activity of SRF617 in cynomolgus 
monkeys was confirmed by an in situ CD39 enzymatic activity assay. 
Preclinical evidence implicates CD39 in murine models of thromboregulation. In 
CD39-haploinsufficient mice, there is an increase in thrombogenesis under certain vascular 
conditions.58 Although no evidence of disordered platelet activation or thrombogenesis was 
detected in SRF617 nonclinical studies, including nonhuman primate toxicology studies, this 
clinical trial will monitor for laboratory evidence of such effects, and all thromboembolic 
adverse events (AEs) will be recorded and monitored as adverse events of special interest 
(AESIs). 
SRF617 is not an immune system agonist, and no increases in cytokines were observed in vivo in 
the 4-week GLP toxicology study. In an in vitro cytokine release assay in PBMCs isolated from 
healthy human donors, SRF617 induced secretion of interleukin (IL)-8 at assay concentrations of 
≥ 100 µg/mL and tumor necrosis factor alpha (TNFα) at ≥ 1000 µg/mL, up to 7.6 times and 
2.8 times, respectively, compared with negative control. At the highest assay concentrations of 
10,000 µg/mL, SRF617 induced secretion of IL-1β, IL-6, IL-8, and TNFα from 28.1x to 77.6x. 
This concentration is approximately 30x greater than the human serum concentrations achieved 
with the recommend Phase 2 starting dose of 1400 mg. Although cytokine release did not occur 
at dose levels relevant to clinical doses, these models are not necessarily predictive of the 
response that may be observed in patients with significant circulating tumor cells.  
Further details on the nonclinical development of SRF617 are available in the current version of 
the SRF617 Investigator’s Brochure. 
1.4.2. 
Rationale to Combine SRF617 With PD-1 Blockade 
There is rationale for combining SRF617 with diverse classes of anticancer agents, including 
immune-checkpoint inhibitors. Immune-checkpoint blockade with anti-PD-1/programmed death-
ligand 1 (PD-L1) antibodies are thought to work by activating exhausted CD8+ T cells in the 
TME, which could be further enhanced by removing immunosuppressive adenosine. Nonclinical 
studies have demonstrated that blocking or modulating the immune suppressive adenosine 
pathway in the TME can augment immune responses in combination with PD-1 blockade. A 
recent study showed that CD39 KO mice implanted with both B16F10 syngeneic tumors had 
delayed tumor growth and better survival when treated with an anti-PD-1 antibody.49 Antibody 
inhibitors of CD73 and small molecule inhibitors of the adenosine receptor A2AR were also 
shown to have significantly increased antitumor effects when combined with anti-PD-1 or 
anti-PD-L1 in syngeneic murine tumor models. This further supports the utility of combining 
adenosine-lowering or -blocking agents with checkpoint inhibition. 45, 59, 60 
Internal nonclinical experiments have demonstrated antitumor cooperativity of anti-CD39 
antibody treatment in combination with both PD-1 blockade and chemotherapeutic agents. An 
antimurine CD39 surrogate antibody in combination with an antimurine PD-1 antibody 
significantly decreased tumor growth and increased survival in syngeneic CT26 colorectal 
tumor-bearing mice (Figure 3).61 


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Figure 3: 
An antimurine-CD39 surrogate antibody in combination with an antimurine 
PD-1 antibody increases survival in a syngeneic CT26 tumor model 
 
Abbreviations: BIW = twice a week; IgG1 = immunoglobulin G1; IP = intraperitoneal(ly); mAb = monoclonal 
antibody; n = number; PD-1 = programmed death receptor-1 
Five- to 7-week-old female BALB/c mice were injected with 2.5 × 105 CT-26 tumor cells subcutaneously into the 
right flank and randomized into 4 treatment groups when tumors reached a mean volume of approximately 
50-80 mm3. The groups (n = 16-18 mice/group) were treated IP with either 20 mg/kg isotype control antibody 
(mouse IgG1), 20 mg/kg antimurine CD39 mAb, 10 mg/kg anti–mouse PD-1 antibody (RMP-14), or a combination 
of PD-1 with antimurine CD39 mAb BIW for 3 weeks. Tumors were measured using a caliper BIW, and tumor 
volumes were calculated. Animals in each group were euthanized when they reached an individual tumor volume of 
≥ 2000 mm3 or were necrotic. A Kaplan-Meier curve depicting overall survival is shown here. Statistical 
significance was calculated using the log-rank (Mantel-cox test) (*p < 0.05). 
1.4.3. 
Summary of Clinical Studies of SRF617 
Currently, there is 1 other ongoing SRF617 clinical trial (SRF617-101, NCT04336098), a Phase 
1, open-label, first-in-human, monotherapy and combination therapy dose-escalation, safety, and 
tumor biopsy expansion trial in patients with advanced solid tumors. This trial will enroll 
approximately 100 patients. The combination therapy portion of the trial will evaluate SRF617 in 
combination with gemcitabine + albumin-bound paclitaxel (Abraxane®) or SRF617 in 
combination with pembrolizumab (Keytruda®). The primary objective of this trial is to determine 
the recommended Phase 2 dose (RP2D) as monotherapy and in combination therapy in patients 
with solid tumors, with the primary endpoint of dose-limiting toxicities.  
Further details on the ongoing clinical studies of SRF617 are available in the current version of 
the SRF617 Investigator’s Brochure. 
1.5. 
Etrumadenant (AB928)  
Etrumadenant is the first clinical stage small molecule dual antagonist of both A2aR andA2bR 
and was designed to maximally inhibit the adenosine-driven impairment of tumor-infiltrating 
lymphocytes (mainly through A2aR on CD8+ T cells and NK cells) and myeloid cells (through 
A2bR on dendritic cells and macrophages) in the absence of any agonist activity. Developed 
specifically for the oncology setting, etrumadenant achieves high penetration of tumor tissue, 
robust potency in the presence of high adenosine concentrations, and minimal shift in potency 
*


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from non-specific protein binding. As a result, etrumadenant is hypothesized to uniquely block 
adenosine’s immunosuppressive and cancer cell-intrinsic effects.  
Nonclinical data demonstrate potent inhibition of adenosine receptor-mediated signaling in 
peripheral blood immune cells at plasma levels consistent with those reached in healthy human 
volunteers and cancer patients. Although etrumadenant alone displayed minimal effects on tumor 
growth or on the nature of the immune infiltrate in various mouse models, etrumadenant 
enhanced the antitumor efficacy when administered in combination with standard cancer 
chemotherapy or immunotherapy without additive toxicity. Moreover, etrumadenant provided 
continued benefit in tumor growth inhibition following cessation of the T-cell activating 
combination partner. 
Clinical data show that heavily pretreated patients with metastatic solid tumors have experienced 
clinical benefit with etrumadenant in combination with other anti-cancer agents as defined by 
objective responses or prolonged stabilization of disease.  
Etrumadenant exhibits pharmacokinetics/pharmacodynamics consistent with once-daily dosing 
and has been well tolerated in dose-escalation studies as a single agent and in Phase 1b/2 studies 
administered in combination with chemo/immunotherapy across multiple advanced solid tumor 
indications.62 
The advanced nature of the underlying cancer is associated with clinically significant side effects 
related to the disease under study. Thus far, administration of etrumadenant in cancer patients 
has been well tolerated and in the absence of additive toxicity. The emerging safety profile for 
etrumadenant, together with evidence of clinical benefit across multiple solid tumor types, 
supports a favorable benefit/risk assessment and provides justification for continued clinical 
development of this investigational therapy.63, 64 
Further details on the ongoing clinical studies of etrumadenant are available in the current 
version of the etrumadenant Investigator’s Brochure. 
1.6. 
Zimberelimab (AB122) 
Zimberelimab is a fully human IgG4 monoclonal antibody targeting the human PD-1 immune 
checkpoint. In preclinical and clinical evaluations, zimberelimab has demonstrated 
pharmacokinetics (PK), pharmacodynamics (including receptor occupancy), efficacy, and safety 
that are consistent with currently approved anti-PD-1 therapies. The most advanced trial with 
zimberelimab is entering Phase 2 development for the treatment of first-line metastatic non-small 
cell lung cancer, evaluating zimberelimab in combination with domvanalimab (AB154), an 
anti-TIGIT monoclonal antibody, and etrumadenant. Zimberelimab is also being evaluated as 
monotherapy in a tumor agnostic, biomarker selected Phase 1b trial for cancers with no approved 
anti-PD-1 treatment options. 
Nonclinical data supports its binding to both PD-L1 and PD-L2 and release of the 
immunosuppressive inhibition of the T-cell effector function post exposure to zimberelimab. 
Clinical data from monotherapy treatment in heavily pretreated patients with various advanced 
solid tumors has established tolerable and pharmacokinetically stable dosing regimens of 
zimberelimab intravenously every 2, 3, and 4 weeks. Additional studies in combination with 
etrumadenant and other agents have also established a tolerable combinatory dosing regimen of 


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zimberelimab. Although preliminary safety data from these studies are still maturing and others 
are ongoing, no unique safety risks have been identified for zimberelimab compared to other 
anti-PD-1 agents. However, the risks associated with this drug class are well established given 
significant experience with the approved anti-PD-1 agents such as nivolumab65 and 
pembrolizumab28 and are appropriate for zimberelimab monitoring. The emerging safety profile 
for zimberelimab, together with well-established clinical benefit with this class of agents with 
approvals across multiple tumor types, supports a favorable benefit/risk assessment and provides 
justification for continued clinical development of this investigational therapy. 
Further details on the ongoing clinical studies of zimberelimab are available in the current 
version of the zimberelimab Investigator’s Brochure. 
1.7. 
Rationale for Combining Etrumadenant and Zimberelimab 
The combination of etrumadenant and zimberelimab is currently being evaluated in an ongoing 
Phase 1 trial in patients with advanced solid tumors (NCT03846310). Etrumadenant 
administered together with zimberelimab was well tolerated and demonstrated evidence of 
clinical benefit, including antitumor response and disease stabilization > 6 months, in heavily 
pretreated patients across multiple disease indications.62 
ARC-5 (NCT03629756) is an ongoing, open-label, Phase 1 dose-escalation and dose-expansion 
trial evaluating the safety and tolerability of etrumadenant and zimberelimab in patients with 
advanced malignancies. The dose-escalation phase of the trial is evaluating etrumadenant 
(75 mg, 150 mg, or 200 mg QD) in combination with zimberelimab 240 mg every 2 weeks 
(q2 weeks). The dose-expansion phase is evaluating etrumadenant 150 mg QD and zimberelimab 
240 mg q2 weeks in patients with renal cell carcinoma or mCRPC. Among 11 evaluable patients, 
Investigator-assessed best overall response (according to Response Evaluation Criteria in Solid 
Tumors [RECIST] v1.1) is 1 confirmed partial response (endometrial cancer), 6 stable disease 
(including ovarian cancer [2 patients] as well as colorectal and appendiceal cancers [1 patient 
each]), and 4 progressive disease. The most commonly reported AEs considered at least possibly 
related to etrumadenant have included fatigue, nausea, and diarrhea. The most commonly 
reported AEs considered related to zimberelimab have included fatigue, diarrhea, and increased 
alanine aminotransferase. 
ARC-6 (NCT04381832) is an ongoing open-label, Phase 1b/2 trial evaluating etrumadenant plus 
zimberelimab with or without standard of care docetaxel or enzalutamide in patients with 
mCRPC. Preliminary safety data suggest a safety profile for the combination similar to what has 
been observed thus far in ARC-5. 
1.8. 
Trial Rationale  
While the treatment armamentarium for mCRPC has significantly improved in the last few years 
with next-generation androgen receptor-targeted therapies and chemotherapy, resistance is nearly 
universal. Engaging the patient’s immune system with immune checkpoint blockade and 
targeting the immunosuppressive adenosine pathway that may make for a tumor-permissive 
microenvironment is a rational route to override innate or established resistance mechanisms in 
mCRPC. Dual blockade of the adenosine pathway with proximal inhibition of CD39 with 
SRF617 and distal targeting at the level of the adenosine receptors with the dual A2AR 
antagonist etrumadenant in concert with PD-1 pathway blockade has great potential to induce 


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significant clinical benefit in mCRPC resistant to standard therapies and improve clinical 
outcomes.  
Anti-PD-1 antibodies activate exhausted CD8+ T cells in the TME, an effect that can be 
dampened by the immunosuppressive adenosine within the TME. Nonclinical studies have 
demonstrated that blocking or modulating the adenosine pathway in the TME can augment 
immune responses in combination with PD-1 blockade. In CD39 KO mice implanted with both 
B16F10 syngeneic tumors, delayed tumor growth and better survival was observed after 
treatment with an anti-PD-1 antibody.49 Antibodies against CD73 and small molecule inhibitors 
of the adenosine receptor A2AR have also been shown to significantly increase tumor shrinkage 
when combined with anti-PD-1 or anti-PD-L1 in syngeneic murine tumor models.45, 59, 60 These 
effects are largely attributed to enhanced T-cell activation in the TME. 
In the clinic, preliminary signs of antitumor activity in mCRPC have been observed with several 
adenosine pathway antagonists in combination with PD-1 pathway blockade.66-69 These early 
clinical results, combined with the robust preclinical data, support co-targeting the adenosine and 
PD-1 pathways.45,59,60 The combination of etrumadenant and zimberelimab has already been 
evaluated in early-phase studies across multiple tumor types demonstrating some tumor 
responses and disease stabilization as well as a favorable safety profile. While both SRF617 and 
etrumadenant target the adenosine pathway, the safety profile of both agents appears manageable 
thus far with low-grade fatigue or gastrointestinal (GI) distress as the most common overlapping 
side effects, which will be monitored for any cumulative toxicity and tolerability. Together, the 
safety profiles and strong mechanistic potential for complementary three-way reversal of 
immune suppression and induction of a more hospitable immune milieu provide justification for 
clinical development of this triplet IO therapy.  
1.8.1. 
Selection of Patient Populations 
The population to be studied in this Phase 2 trial includes patients with mCRPC who have 
progressed on or after prior ARSI therapy. 
1.9. 
Determination of Dose and Schedule 
The RP2D of SRF617 monotherapy from Trial SRF617-101 was determined to be 1400 mg, 
based on the totality of safety information, clinical PK/pharmacodynamic relationship, and the 
PK modeling for the biologically active dose using preclinical efficacy models. The dose of 1400 
mg was investigated in Trial SRF617-101 and found to be safe and well-tolerated. Based on 
comprehensive modeling, a dose of 1400 mg will achieve (1) CD39 target occupancy near 
saturation throughout the dosing interval, (2) an SRF617 concentration that is anticipated to 
inhibit CD39 activity in tissues and tumors in human CD39 knock-in mice, and (3) an equivalent 
drug level that resulted in significant tumor growth inhibition in preclinical xenograft efficacy 
models. The SRF617 dose schedule in SRF617-201 will be a q2 week schedule, the same dosing 
frequency as that in SRF617-101; therefore, dose scaling is not planned. In addition, drug-drug 
interactions with SRF617 are not anticipated as etrumadenant is a synthetic, low molecular 
weight drug administered orally and zimberelimab is an antibody targeting the PD-1 pathway 
(different from SRF617’s antibody blocking of the adenosine pathway). Both SRF617 and 
etrumadenant target the adenosine pathway at different levels and have good tolerability as 
single agents with low-grade fatigue and GI distress being the most common overlapping side 


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effects of these agents reported thus far. Cumulative toxicity of dual targeting this pathway will 
be monitored. Therefore, given the lack of anticipated safety or tolerability concerns with the 
combination of SRF617, etrumadenant, and zimberelimab, the SRF617 RP2D of 1400 mg as 
determined in Trial SRF617-101 will be employed as the starting dose in SRF617-201. 
In order to establish the optimal SRF617 dose and schedule in SRF617-201, the Sponsor may 
consider evaluating an alternative dose level or dose schedule, as recommended by  the Safety 
Review Committee (SRC)’s safety review of the monotherapy and combination therapy data. 
The proposed dose of zimberelimab is 480 mg administered IV every 4 weeks (q4 weeks). In the 
first-in-human study of zimberelimab, AB122CSP001, zimberelimab doses of 80 mg, 240 mg, 
and 360 mg q2 weeks, 360 mg every 3 weeks, and 480 mg and 720 mg q4 weeks were 
administered as monotherapy to patients with advanced malignancies. All doses mentioned 
above were found to be safe and well-tolerated, and no maximum tolerated dose was reached. 
PK data were gathered from all subjects after first dose and at steady-state and were used to 
develop a population PK model. Simulations were performed using the population PK model to 
identify appropriate doses for Phase 2 and Phase 3 studies. The dose of 480 mg q4 weeks was 
found to result in steady-state concentrations at trough > 15 µg/mL in a majority of patients. This 
concentration was identified as the target effective concentration that would result in > 99% 
peripheral receptor occupancy of PD-1 receptors, a level of target occupancy that is widely 
believed to result in maximal efficacy.  
The proposed dose of etrumadenant is 150 mg administered orally every day. In the 
first-in-human study of etrumadenant, AB928CSP001, doses up to 200 mg once daily were 
administered as a single agent. Overall, the doses were found to be safe and well-tolerated and a 
maximum tolerated dose for etrumadenant was not identified in the study. Subsequently, 
etrumadenant was administered at doses of 75 mg and 150 mg once daily in combination with 
pegylated liposomal doxorubicin with and without IPI-549. Overall, no major safety concerns 
were identified at this dose. A pharmacodynamic measure was also incorporated in these studies. 
Levels of phosphorylated cAMP response element-binding protein (pCREB) were assessed by flow 
cytometry, both in the absence of and following ex vivo stimulation with the adenosine receptor 
agonist 5′-N-ethylcarboxamide adenosine (NECA). The dose of 150 mg was identified as the dose 
for Phase 2 expansion studies since it resulted in near maximal reduction in pCREB in both 
healthy subjects and cancer patients. Subsequently, the dose of 150 mg has been used in other 
studies in cancer patients; no new concerns regarding safety of this dose have been identified.  
Additional information regarding administration of SRF617, etrumadenant, and zimberelimab is 
described in Section 7 and in the SRF617-201 Pharmacy Manual. 
 


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2. 
OBJECTIVES 
2.1. 
Primary Objectives 
• To evaluate the preliminary efficacy of SRF617 administered in combination with 
etrumadenant and zimberelimab as determined by objective response and PSA 
decline 
• To evaluate the safety and tolerability of the combination 
2.2. 
Secondary Objectives 
• To evaluate additional preliminary efficacy parameters of the combination including 
ORR, PSA response, clinical benefit, duration of response (DoR), and radiologic PFS  
• To evaluate the PK of SRF617 when administered in combination with etrumadenant 
and zimberelimab 
• To characterize additional safety parameters including development of antidrug 
antibodies (ADAs) and symptomatic skeletal events (SSEs) 
2.3. 
Exploratory Objectives 
• Explore potential biomarkers of response and/or safety of the combination 
• Explore the effects of the triplet on peripheral blood immune cell subsets and 
circulating serum cytokines and chemokines  
• Explore the biological effects of the triplet on tumor cells and immune cell 
populations in the TME 
• Explore germline DNA polymorphic variations in relation to the PK, 
pharmacodynamics, safety, and/or preliminary efficacy  
• Explore correlations between prostate cancer biomarkers in tumors with biomarkers 
in serum in patients who undergo tumor biopsy  
• Explore correlations between prostate cancer biomarkers in tumors with clinical 
response parameters in patients who undergo tumor biopsy 
 


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3. 
ENDPOINTS 
3.1. 
Primary Endpoints 
• The proportion of patients with a response, defined as PSA50 response (≥ 50% 
decline) and/or radiographic objective response of complete response (CR) or partial 
response (PR) per Prostate Cancer Working Group (PCWG3) criteria  
• Incidence and severity of AEs 
3.2. 
Secondary Endpoints 
• ORR per PCWG3 criteria, ORR per RECIST v1.1, duration of response, disease 
control rate (DCR), PSA50 response, PSA decline ≥ 30% (PSA30) response, time to 
PSA progression, radiographic PFS, and landmark PFS rate at 6 and 12 months 
• Serum concentrations of SRF617 
• Percentage of patients with ADAs to SRF617  
• Incidence of SSEs 
3.3. 
Exploratory Endpoints  
• Changes in selected blood and tumor tissue biomarkers  
• Germline DNA polymorphic sequence variations in relation to the PK, 
pharmacodynamics, safety, and/or preliminary efficacy of SRF617 
• Serum PAP levels 
• PAP expression levels in tumors in patients who undergo tumor biopsy  
• PD-L1 and CD39 expression levels in tumors in patients who undergo tumor biopsy 


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4. 
TRIAL DESIGN 
This is a Phase 2, open-label, safety and preliminary efficacy trial in patients with mCRPC who 
have progressed on or after prior ARSI therapy. The trial will enroll approximately 40 patients. 
A patient is enrolled in the trial after they have provided informed consent and met all trial 
eligibility criteria. 
The trial will employ a Simon 2-stage design with an integrated safety lead-in for the triplet 
combination of SRF617, etrumadenant, and zimberelimab. Cycles are 28 days in duration.  
Tumor biopsies are optional; they will be performed to explore potential biomarkers of response 
to the combination in patients who consent to the procedure, who have non-bone metastases 
amenable to biopsy, and for whom the procedure is deemed safe. 
Patients will continue to receive study drug for up to 2 years or until documented disease 
progression or unacceptable toxicity (Section 4.7). Patients may remain on study drug longer 
than 2 years with agreement from the trial Investigator and Sponsor.  
4.1. 
Stage 1 
Stage 1 will enroll approximately 17 patients, including the Safety Lead-in that will initially treat 
6 patients. After the first 6 patients have been enrolled, enrollment will be paused until these 
patients have received 1 cycle of the triplet combination and the SRC has reviewed the aggregate 
safety data. Once the SRC deems it safe to proceed, an additional 11 patients will be enrolled.  
To be considered evaluable for the Safety Lead-in, patients must have completed at least 50% of 
the prescribed doses of all 3 drugs during the review period (Day 1-28 = Cycle 1) and must not 
have discontinued treatment during Cycle 1 for reasons other than drug-related AEs. For 
example, patients who discontinued study treatment during Cycle 1 for progressive disease or for 
patient or physician preference but without experiencing a Grade ≥ 3 related toxicity would not 
be considered fully evaluable for the Safety Lead-in and would be replaced. A ‘related’ toxicity 
is defined as those toxicities assessed by the Investigator to be possibly, probably, or definitely 
related to any study drug.  
4.2. 
Stage 2 
Based on an evaluation of safety and response data, the trial will proceed to the Stage 2 
expansion if ≥ 1 radiographic CR/PR or 2 PSA responses (defined as a ≥ 50% decline [PSA50]) 
according to PCWG3 criteria are observed in 17 evaluable patients. An additional 23 patients 
will be enrolled in Stage 2 for further evaluation of the safety and efficacy of the combination.  
4.3. 
Safety Review Committee 
This trial will use an SRC, which will meet regularly throughout the trial to review all available 
safety, PK, and preliminary efficacy data. The SRC will be composed of a medical representative 
from the Sponsor, a Medical/Safety Monitor from the Contract Research Organization 
supporting the trial (if applicable), and all Principal Investigators (or their specified delegates) at 
each of the enrolling sites. The SRC may recommend investigating intermediate doses or 
alternative schedules for administration of SRF617 to optimize combination dose determination. 
The SRC may recommend halting or stopping the trial at any time based on a comprehensive 
review of all clinical data. 


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4.4. 
Dosing Frequency 
SRF617 will be administered in combination with etrumadenant and zimberelimab in 28-day 
cycles according to the following dosing schedule: 
• SRF617 1400 mg IV q2 weeks on Days 1 and 15 
• Etrumadenant 150 mg orally daily 
• Zimberelimab 480 mg IV q4 weeks on Day 1 
4.5. 
Monitoring of Adverse Events 
All patients will be monitored continuously for toxicity while on study drug. AE severity will be 
assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events 
(NCI-CTCAE) version 5.0, or higher. If a patient has an AE of a particular severity or an AE at 
least possibly related to study drug, then dose modifications should be made according to the 
guidelines set forth in the trial protocol (see Section 7.4). 
4.6. 
Trial Stopping Rules 
The following safety stopping rule will also be applied during the Safety Lead-in: If 2 or more of 
these 6 patients experience a Grade ≥ 3 related AE (with the exception of toxicities listed in 
Table 4), any treatment-related toxicity that causes the participant to discontinue treatment 
during Cycle 1, or prolonged delay (>14 days in initiating Cycle 2 due to toxicity), the trial will 
be halted for SRC review. 
Table 4: 
Stopping Rule Exceptions 
The following Grade ≥ 3 toxicities considered at least possibly related to study treatment would not be 
considered to meet criteria for a safety stopping rule:  
Nausea 
Any Grade ≥ 3 event responding to supportive treatment within 3 days 
Vomiting 
Diarrhea 
Fatigue 
Grade ≥ 3 lasting < 7 days 
Asymptomatic 
amylase/lipase elevations 
Grade ≥ 3 lasting any duration if asymptomatic and no clinical signs of 
pancreatitis 
Thyroid function 
abnormalities (eg, hypo- or 
hyperthyroidism) 
Grade ≥ 3 lasting any duration if can be controlled with treatment such 
as thyroid supplementation or beta blockade 
Rash 
Grade ≥ 3 recovering to Grade 1 with treatment (ie, steroids) within 7 
days 
Alopecia 
Grade ≤ 2 lasting any duration 
Non-hematologic laboratory 
abnormalities 
Clinically nonsignificant, treatable, or reversible laboratory 
abnormalities including liver function tests, electrolytes, uric acid, etc.  


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4.7. 
Treatment Discontinuation 
A patient should be discontinued from a study drug if, in the opinion of the Investigator or 
Sponsor, it is medically necessary or if it is the wish of the patient. Discontinuation of study 
treatment does not represent withdrawal from the trial. 
All patients should undergo the Safety Follow-up visit when they discontinue the last study drug 
(Section 6.4). 
Patients will be discontinued from all study drugs for any of the following reasons: 
• AE(s) that requires permanent discontinuation of all study drugs 
• Disease progression as measured by the appropriate response criteria  
− Note: Patients who meet criteria may continue past disease progression (see 
Section 6.3) 
• Noncompliance with protocol  
• Investigator decision (specific justification to be documented) 
• Patient is lost to follow-up  
• Termination of the trial by the Sponsor 
• Voluntary withdrawal by patient  
AEs leading to the discontinuation of study drug will be followed until resolution to Baseline or 
until the event is considered stable or chronic. Patients who discontinue treatment with any study 
drug for any reason, but who are deriving clinical benefit (objective response or stable disease) 
from one or both of the remaining drugs, may continue to receive those study drugs at the 
discretion of the Investigator and Sponsor.  
The End of Treatment (EoT) visit should occur within 7 days after a patient discontinues the last 
study drug. Disease response assessment is not required for patients whose most recent scan was 
≤ 6 weeks before the EoT visit. Other assessments previously performed within the previous 
2 weeks need not be repeated at EoT. For patients who discontinue the last study drug because of 
a treatment interruption lasting ˃ 56 days, the EoT visit should be completed as soon as possible.  
All patients will have a Safety Follow-up visit at 30 days after the last dose of SRF617, 30 days 
after the last dose of etrumadenant, or 90 (+ 7) days after the last dose of zimberelimab (30 days 
after the last dose of zimberelimab if the patient initiates new anticancer therapy), whichever is 
later. If possible, this visit should occur before the initiation of any subsequent anticancer 
therapy. At a minimum, this visit should include collection of AEs and concomitant 
medications/procedures.  
Response assessments will be conducted per Table 2 until the patient experiences progressive 
disease or discontinues the trial. 
 
 


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4.8. 
Trial Withdrawal 
Patients may voluntarily withdraw from the trial at any time for any reason without prejudice.  
Patients will be withdrawn from the trial for any of the following reasons: 
• Patient death 
• Patient lost to follow-up  
• Termination of the trial by Sponsor 
• Voluntary withdrawal of consent by patient 
If the patient withdraws consent from the overall trial participation (and not just study drug), no 
further evaluations should be performed and no attempts should be made to collect additional 
data. 


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5. 
TRIAL POPULATION 
5.1. 
Inclusion Criteria 
All patients must meet the following criteria for inclusion: 
1. Males ≥ 18 years of age on the day of signing informed consent. 
2. Metastatic castration-resistant prostate cancer with castrate levels of testosterone 
(≤ 50 ng/dL or ≤ 1.7 nmol/L). 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 
4. Must have progressed (by PSA or radiologic criteria) during or following treatment with 
a novel ARSI (eg, abiraterone, enzalutamide, apalutamide, darolutamide), which may 
have been given for either hormone-sensitive prostate cancer (HSPC) or CRPC.  
5. Must have received 1 to 2 prior lines of taxane chemotherapy, unless the physician and 
patient believe the patient is medically ineligible or the patient refuses (ineligibility or 
refusal must be documented in the source documents). 
6. Must have progressed by PSA or radiologic criteria on or during last therapy for prostate 
cancer. 
7. Measurable or non-measurable disease as per radiographic evaluation. Lesions situated in 
a previously irradiated area are considered evaluable if progression has been 
demonstrated in such lesions since radiation. 
• Note: If disease is considered non-measurable, a minimum PSA of 1 ng/dL is 
required with at least 1 confirmed rise at a minimum of a 1-week interval. 
8. Washout period from the last dose of previous anticancer therapy (chemotherapy, 
biologic, or other investigational agent) to the first dose of study drug must be > 5 times 
the half-life of the agent or > 21 days, whichever is shorter. The washout period for 
palliative radiation (defined as ≤ 2 weeks of radiation) to non-central nervous system 
(CNS) disease is > 7 days. 
9. Resolution of non-immune-related AEs secondary to prior anticancer therapy (excluding 
alopecia and peripheral neuropathy) to Grade ≤ 1 per NCI-CTCAE version 5.0 or higher, 
and complete resolution of immune-related AEs secondary to prior immunotherapy. 
• Note: Patients with the following clinically stable or clinically nonsignificant 
immune-related AEs are permitted: Controlled thyroid disorders, vitiligo, 
asymptomatic elevated amylase/lipase, type 1 diabetes on insulin, Grade ≤ 2 
controlled rash, Grade ≤ 2 electrolyte abnormalities on stable dose of 
supplementation. 
10. Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.5 × 
109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 × 109/L. Transfusions are 
permitted to meet hemoglobin and platelet criteria. However, the patient must have a 
stable hemoglobin level and platelet count for ≥ 2 weeks prior to dosing without 
transfusion. 


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11. Adequate renal function, defined as serum creatinine clearance ≥ 30 mL/min per 
Cockcroft-Gault formula. 
12. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 3 × ULN if elevated because of 
Gilbert’s syndrome, and ≤ 2 × ULN for patients with known liver metastases). 
13. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN 
(< 5 × ULN if liver metastases present). 
14. Prothrombin time (PT) or international normalized ratio (INR) and activated partial 
thromboplastin time (aPTT) ≤ 1.5 × ULN unless the patient is receiving anticoagulant 
therapy, in which case PT/INR or aPTT must be within therapeutic range of intended use 
of anticoagulants. 
15. Willingness of male patients who are not surgically sterile to use medically acceptable 
methods of birth control for the duration of the study treatment period, including 30 days 
after the last dose of SRF617, 30 days after the last dose of etrumadenant, or 90 days 
after the last dose of zimberelimab, whichever is later; male patients must refrain from 
donating sperm for 4 months after the last dose of any study drug. Sexually active men, 
when having sexual intercourse with a female of reproductive potential, should use an 
efficient barrier contraceptive (condom plus spermicide); the respective partner should 
also use an additional efficient contraceptive method (eg, oral pills, intrauterine device, or 
diaphragm, and spermicide). 
16. Ability to adhere to the trial visit schedule and all protocol requirements. 
17. Institutional review board (IRB)/independent ethics committee (IEC)-approved informed 
consent form (ICF) signed and dated by patient (or legally acceptable representative if 
applicable) before any Screening procedures are performed. 
5.2. 
Exclusion Criteria 
Patients are to be excluded from the trial if they meet any of the following criteria: 
1. Currently participating in or has participated in a trial of an investigational device or has 
used an investigational device within 21 days before the first dose of study drug. 
2. Any component of small cell or neuroendocrine histology. 
3. Previously received an anti-CD39 antibody, anti-CD39 targeted therapy, or other agent 
targeting the adenosine pathway. 
4. Prior treatment with PD-L1/PD-1 inhibitors. 
5. Prior treatment with ≥ 3 lines of taxane chemotherapy administered as a single agent or 
as part of a combination regimen. 
6. Symptomatic or untreated brain metastases (including leptomeningeal metastases). 
Patients previously treated for brain metastases must be at least 4 weeks from completion 
of radiation treatment with follow-up imaging showing no progression. 
7. Current pneumonitis with or without steroid requirement or history of pneumonitis 
requiring steroids. 


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8. Another malignancy other than prostate within 2 years of trial entry, except for those with 
a low risk of spreading or negligible risk of death such as non-melanoma skin cancer or 
Ta superficial bladder cancer. 
9. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with 
use of disease modifying agents, corticosteroids, or immunosuppressive drugs). 
10. Medical conditions requiring chronic steroid (ie, > 10 mg/day of prednisone or its 
equivalent). 
• Note: Replacement therapy (eg, levothyroxine, insulin, or physiologic 
corticosteroid replacement therapy for thyroid, adrenal, or pituitary insufficiency) 
is allowed. 
11. Concomitant therapy with agents that may have potential drug-drug interactions with 
etrumadenant: 
a) Known P-glycoprotein (P-gp) substrates with a narrow therapeutic window, 
administered orally (eg, digoxin) within 4 weeks or 5 half-lives of the drug 
(whichever is shorter) prior to initiation of study treatment. 
b) Known strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, 
phenobarbital, and St. John’s Wort) and strong CYP3A4 inhibitors (eg, 
clarithromycin, itraconazole, ketoconazole, posaconazole, telithromycin, and 
voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is shorter) 
prior to initiation of study treatment. 
c) Known breast cancer resistance protein (BCRP) substrates with a narrow 
therapeutic window, administered orally (eg, prazosin, rosuvastatin) within 4 
weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study 
treatment. 
d) Additional substrates, inhibitors, and inducers with the potential for drug-drug 
interactions with etrumadenant within 4 weeks or 5 half-lives of the drug 
(whichever is shorter) prior to initiation of study treatment. Refer to Appendix 1 
and the following: https://www.fda.gov/drugs/drug-interactions-labeling/drug-
development-and-drug-interactions-table-substrates-inhibitors-and-inducers. 
12. History of Grade ≥ 3 allergic or anaphylactic reaction to any monoclonal antibody 
therapy, any excipient in the study drugs, or fusion proteins. 
13. Prior hematopoietic stem cell or solid organ transplant. 
14. Known current or prior infection with HIV, hepatitis B virus (HBV), or current infection 
with hepatitis C virus (HCV).  
• Exception: Controlled active HBV or fully treated HCV infection is permitted. 
Antiviral therapy as per local standard of care should be continued. 
− Controlled disease is considered HBV DNA < 500 IU/mL during the Screening 
Period with willingness to continue antiviral treatment during the length of the 
trial. The patient must be on anti-HBV treatment (per local standard of care; eg, 
entecavir) for a minimum of 14 days prior to trial entry. 


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− For patients with HCV, only cured disease or HCV considered fully treated and 
no longer requiring antiviral therapy for control is permitted.  
− No co-infection with HCV and HBV is allowed. HCV and HBV co-infection is 
defined as HCV RNA positive and hepatitis B surface antigen (HBsAg) positive 
and is excluded. However, a patient who is hepatitis C antibody (HCV Ab) 
positive,  hepatitis B core antibody (HBcAb) positive, but negative HBsAg is not 
considered co-infection and is permitted. 
15. Administration of a live attenuated vaccine within 6 weeks before the first dose of study 
drug. 
• Exception: Health Authority approved COVID-19 vaccines are permitted. 
16. Baseline QT interval corrected (QTc) with Fridericia’s method 
(QTcF) ≥ 480 milliseconds. This criterion does not apply to patients with a right or left 
bundle branch block. 
17. History of unstable angina or ventricular arrhythmia requiring medication or mechanical 
control within 6 months before Screening. 
18. History of major thromboembolic event (eg, stroke, myocardial infarction, pulmonary 
embolism) ≤ 6 months before the first dose of study drug.  
• Exception: Patients with history of deep vein thrombosis (DVT) are permitted if 
they are on stable anticoagulation treatment for at least 3 months before the first 
dose of study drug.  
19. Any gastrointestinal condition that would preclude the use of oral medications (eg, 
difficulty swallowing, nausea, vomiting, or malabsorption). 
20. Major surgery within 4 weeks before Screening. 
21. Ongoing, uncontrolled, systemic bacterial, fungal, or viral infections at Screening. Oral 
antibiotics for a controlled infection are permitted. Patients on antimicrobial, antifungal, 
or antiviral prophylaxis are not excluded if all other inclusion and exclusion criteria are 
met. No severe infection within 4 weeks before first dose. 
22. Unstable or severe, uncontrolled medical condition, important medical illness, abnormal 
laboratory finding, or psychological condition, that would, in the Investigator’s judgment, 
increase the risk to the patient associated with participation in the trial or interfere with 
safe completion of the trial. 


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6. 
TRIAL PROCEDURES AND ASSESSMENTS 
Time points for assessments to be collected throughout the trial can be found in the following 
tables: 
• Table 1: 
Screening Assessments Checklist  
• Table 2: 
Schedule of Assessments: SRF617 + Etrumadenant + Zimberelimab 
Combination Therapy  
• Table 3: 
Schedule of Pharmacokinetic and Antidrug Antibody Assessments for 
Combination Therapy  
A brief description of all assessments is presented in Section 6.1.  
6.1. 
Procedures and Assessments 
All potential patients will undergo Screening assessments to determine trial eligibility. Patients 
who do not meet Screening criteria may be rescreened later within the initial Screening Period 
(ie, ≤ 30 days from first dose) to confirm eligibility. If rescreening occurs after the initial 
Screening Period, sites should contact the trial Medical Monitor for approval. During the 
Screening Period, a patient number will be assigned. 
6.1.1. 
Informed Consent 
Patients potentially eligible for participation must sign an ICF before initiating any trial-specific 
procedures. Standard of care assessments that fulfill trial eligibility requirements may be 
performed before the patient signs the ICF. 
6.1.2. 
Inclusion and Exclusion Criteria 
Inclusion and exclusion criteria (Section 5.1 and Section 5.2, respectively) will be reviewed for 
each potential patient and documented in the patient medical record and electronic case report 
form (eCRF).  
6.1.3. 
Medical History, Demographics, Disease Characterization, and Cancer History 
Each patient’s complete medical history will be obtained, including demographics, cancer 
history (eg, date of prostate cancer diagnosis, date of metastatic disease diagnosis, date when the 
disease became castrate resistant, and castrate-resistant status [chemical vs. surgical]), disease 
characterization (eg, Gleason score at diagnosis [≤ 6, 7, ≥ 8], distribution of metastatic disease at 
trial entry [eg, bone, lymph node, visceral disease (lung or liver), other soft tissue], number of 
bone metastases [0, 1 to 4, 5 to 9, 10 to 20, > 20], pain [yes/no/NA], and when available: tumor 
genomics [eg, microsatellite instability-high/deficient mismatch repair, DNA repair pathway 
alterations such as BRCA1/2, ATM, PALB2] or PD-L1 immunohistochemistry status), and 
documentation of all previous treatments and treatment results, ie, best response to previous 
prostate cancer treatments.  
6.1.4. 
Prior/Concomitant Medications and Procedures 
At Screening, concomitant and previous medications and procedures will be assessed including 
all medications/procedures that have occurred within the previous 30 days (previous 6 weeks for 


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live attenuated vaccines). In addition, any cancer treatment procedures from any time in the past 
(eg, radiation, surgical resection) should be captured under prior procedures. Assessment of any 
change in concomitant medications or procedures since the last visit will occur at all further 
patient visits through Safety Follow-up. 
6.1.5. 
Physical Examination 
A full physical examination will be performed at Screening and will include vital signs 
(temperature, blood pressure [sitting for 5 minutes], pulse, and respiratory rate), height, and 
weight, as well as a systematic physical examination; this will constitute the Baseline 
examination. If vital signs need to be repeated during a single visit, assessments should be 
conducted approximately 5 minutes apart. Clinically significant findings at Screening should be 
recorded as medical history. 
After Screening, physical examination will be symptom directed and will include collection of 
vital signs; vital signs will be collected at each clinic visit. Results from the symptom-directed 
physical examinations will be used for assessment of disease response. Any new clinically 
significant abnormality or worsening conditions from Baseline should be recorded as an AE. 
6.1.6. 
Eastern Cooperative Oncology Group Performance Status  
ECOG performance status will be assessed at Screening and frequently during the study 
treatment period, as well as at the EoT and 90-day Safety Follow-up visits. If the ECOG 
performance status assessed at Screening is performed within 7 days before the first dose 
(Cycle 1 Day 1 [C1D1]), the Screening assessment can be used and does not need to be repeated. 
Refer to Appendix 2 for a sample of the ECOG assessment.  
6.1.7. 
Electrocardiogram 
At Screening, a standard 12-lead electrocardiogram (ECG) will be conducted after an 
approximately 10-minute rest period in all patients and will be interpreted by the Investigator to 
confirm eligibility. QTc measurements will use Fridericia’s correction method (QTcF). Patients 
with Screening/Baseline QTcF ≥ 480 milliseconds will be excluded from trial participation (see 
Section 5.2 for additional details). Subsequent ECGs will only be conducted if clinically 
indicated, per Investigator discretion. 
6.1.8. 
Clinical Laboratory Tests 
The following laboratory parameters will be measured as indicated at Screening (Table 1) and/or 
throughout the treatment period (Table 2), as appropriate for the site, and will be analyzed 
locally: 
• Blood chemistry laboratory parameters, including sodium, potassium, chloride, 
bicarbonate (or carbon dioxide), blood urea nitrogen or urea, creatinine, calcium, 
phosphorous, magnesium, glucose, albumin, and total protein 
• Liver function tests, including serum ALT, serum AST, total and direct bilirubin, and 
alkaline phosphatase 
• Pancreatic tests, including amylase and lipase 


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• Hematology laboratory parameters, including hemoglobin, hematocrit, red blood cell 
(RBC) count, and white blood cell count with differential, including ANC, absolute 
lymphocyte count, platelet count, and reticulocyte count  
• Coagulation laboratory parameters, including PT and aPTT 
− For patients receiving anticoagulation therapy affecting prothrombin time, an INR 
must be obtained. For patients receiving anticoagulation therapy affecting PT/INR 
or aPTT, these laboratory parameters should be monitored serially during the trial. 
• Thyroid function tests, including thyroid stimulating hormone and free thyroxine 
• Complete urinalysis with qualitative analysis for protein 
• PSA 
• PAP 
• Lactate dehydrogenase (LDH) 
• Testosterone 
Unscheduled assessments should be done as clinically indicated. 
Clinically significant laboratory findings at Screening should be recorded as medical history. 
Clinically significant laboratory findings identified after Screening, including but not limited to 
those findings resulting in a drug interruption/hold/reduction/discontinuation or medical 
intervention, should be reported as AEs (see Section 8.1.1 for the definition of an AE).  
6.1.9. 
Additional Screening Laboratory Measurements 
At Screening, the following assessments will be performed to determine eligibility: 
Hepatitis:  
• All patients will be tested for anti-HCV Ab and HBsAg at Screening. If Ab test is 
positive, hepatitis C RNA (viral load) or HBV DNA will be collected. Patients with a 
positive anti-HCV and HCV RNA titer or HBsAg test will be excluded from 
enrolling in the trial (except for patients with controlled viral disease as outlined in 
eligibility criteria). While HCV and HBV co-infection is defined as HCV RNA 
positive and HBsAg positive and is excluded, a patient who is HCV Ab+, HBcAb+ 
but negative HBsAg is not considered co-infection and is permitted. 
HIV: 
• Patients without documentation of a prior negative HIV test result (eg, antibody, 
antigen or polymerase chain reaction-based test) are required to undergo HIV testing 
during Screening. Only patients with negative HIV results will be eligible to enroll. 
6.1.10. 
Tumor Evaluation 
Quantification of Baseline disease burden should be performed at Screening (Table 1) and 
on-trial tumor response evaluated as outlined in the Schedule of Assessments (Table 2).  


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Assessments of Baseline disease burden, response, and disease progression will be evaluated 
using PCWG3 criteria and RECIST v1.1. See Section 6.3 for additional information about 
specific tests to be performed while on trial. See Appendix 3 for details about the PCWG3 
criteria and RECIST v1.1. 
6.1.11. 
Tumor Biopsies 
Fresh tumor biopsies are optional and will be performed in patients who consent to the 
procedure, who have non-bone metastases amenable to biopsy, and for whom the procedure is 
deemed safe. Tumor biopsies may be performed for any accessible non-bone tumor during the 
Screening period and again any time after dosing during Cycle 2 or at EoT, whichever visit 
comes first. A + 7-day window for scheduling is permitted for EoT biopsies.  
Fresh tumor tissue biopsies may be performed at the time points outlined in Table 1 (Screening) 
and Table 2.  
Archival tumor tissue collection is required for all patients unless an exception is granted with 
Sponsor approval. Refer to the Laboratory Manual for details on sample handling procedures and 
shipping requirements for fresh tumor biopsy samples and archival tumor tissue samples. 
6.1.12. 
Pharmacokinetic Sampling 
PK sample collection time points are shown in Table 3. Serum samples will be analyzed for 
SRF617 and zimberelimab concentrations. Plasma samples will be analyzed for etrumadenant. 
The date and time of each sample collection, and the date and time of the prior study drug dose, 
must be recorded for all collected samples. 
An additional PK sample, beyond those listed in Table 3 may be requested (when feasible) at the 
time of any unusual safety event (ie, an AE different in type and severity from that which is 
expected in the setting of SRF617, etrumadenant, or zimberelimab use), or if a sample is found 
to be compromised.  
Refer to the Laboratory Manual for details on sample handling procedures and shipping 
requirements for PK samples. 
6.1.13. 
Biomarker Assessments 
Samples will be collected for biomarker analysis to investigate the biological effects of SRF617 
at the molecular and cellular level, as well as to evaluate how changes in the markers and 
immune cell populations may relate to exposure and clinical outcomes. The goal of the 
biomarker assessments is to provide supportive data for the clinical trial. There may be 
circumstances when a decision is made to stop a collection, not perform, or discontinue an 
analysis because of either practical or strategic reasons, eg, inadequate sample number, sample 
quality issues precluding analysis. Therefore, sample collection and/or analysis may be omitted 
at the discretion of the Sponsor. The timing around collection of these assessments is outlined in 
Table 1 (archival tumor tissue) and Table 2. 
Additional biomarker samples beyond those listed in Table 2 may be requested (when feasible) 
at the time of any unusual safety event (ie, an AE different in type and severity from that which 


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is expected in the setting of SRF617, etrumadenant, or zimberelimab use), or if a sample is found 
to be compromised. 
The following biomarker samples may be analyzed at a central laboratory or a specialized 
laboratory vendor: 
• Blood (PBMCs) for immunophenotyping and immune monitoring: 
− To monitor the effects of treatment on various peripheral blood immune cell 
populations, PBMC immunophenotyping by flow cytometry analysis will be used 
for quantitation and to assess relative frequency of various immune cell subsets. 
Subsets may include, but are not limited to, monocytes, neutrophils, myeloid-
derived suppressor cells, and T/B/NK-cell populations.  
• Blood for cytokine/chemokine/soluble factors: 
− For profiling of potential predictive and pharmacodynamic biomarkers of 
response and/or resistance to SRF617. 
− Serum levels of soluble factors associated with cancer and immunological 
function will be assessed. Examples include, but are not limited to, MCP-1 
(CCL2), TNFα, MIP-1α (CCL3), MIP-1β (CCL4), IL-1β, interferon (IFN)γ, IL-
10, IL-8, IL-6, and IL-2.  
• Archival tumor tissue and fresh tumor biopsy tissues, when available: 
− For assessment of potential predictive biomarkers in the tumor and TME. 
− In situ examination of markers on tumor cells, distinct immune cell populations, 
and other nontumor cellular compartments (eg, stroma) by immunohistochemistry 
may include, but are not limited to, CD39, PD-L1, and T-cell and macrophage 
populations as assessed by various immune cell markers (eg, CD8 and CD68). 
− Gene expression evaluation of tumor-specific and immune-related genes and/or 
gene signatures.  
Samples collected during the trial will banked for up to 10 years. Any remaining material, as 
permitted, may be used to conduct research related to either SRF617 and CD39-relevant 
pathways, or to cancer biology in general. 
Refer to the Laboratory Manual for biomarker sample handling procedures and shipping 
requirements. 
6.2. 
Safety Assessments 
6.2.1. 
Adverse Events 
Serious adverse events (SAEs) will be immediately reported from the time of signing the ICF 
until the Safety Follow-up visit, 30 days after the last dose of SRF617, 30 days after the last dose 
of etrumadenant, or 90 days after the last dose of zimberelimab (30 days after the last dose of 
zimberelimab if the patient initiates new anticancer therapy), whichever is later, or until the 
patient has been deemed to be a screen failure. At any time after completion of the AE reporting 


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period, if an Investigator becomes aware of an SAE that the Investigator considers to be related 
to any study drug, the event must be reported.  
Nonserious AEs will be monitored from the time of the first dose of study drug through 30 days 
after the last dose of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the 
last dose of zimberelimab (30 days after the last dose of zimberelimab if the patient starts another 
anticancer therapy), whichever is later. After the patient is enrolled, all AEs will be captured on 
the eCRF. 
See Section 8.2 for a full description of the collection and reporting of AEs during this trial. 
6.2.2. 
Antidrug Antibody Assay 
An ADA assay will be performed at a central laboratory for SRF617 immunogenicity testing. 
Refer to the Laboratory Manual for sample handling procedures and shipping requirements. 
ADA assays will also be performed for zimberelimab, with sparse sampling throughout the trial. 
The time points for the collection of this assessment are detailed in Table 3. An additional ADA 
sample, beyond those listed, may be requested (when feasible) at the time of any unusual safety 
event, ie, an AE different in type and severity from that which is expected in the setting of 
SRF617, etrumadenant, or zimberelimab use. Patients who test positive for SRF617 ADA will be 
tested until their ADA levels revert to Baseline or the end of the trial. 
6.3. 
Response Assessment Procedures 
For all parts of the trial, response and progression will be determined by Investigator assessment 
at the time points shown in Table 2 as compared with Baseline tumor evaluation (see 
Section 6.1.10) performed in Screening assessments (Table 1). The modality chosen to evaluate 
each individual patient should be the same throughout the duration of the trial. Redacted images 
may be collected. 
Of note, for patients who achieve a CR or PR, a follow-up response assessment should be 
performed after at least 4 weeks to confirm the response. Patients will be expected to continue to 
follow the response assessment schedule as outlined in the Schedules of Assessments. 
These evaluations will be conducted until the patient experiences progressive disease or 
discontinues the trial. See Section 6.3.1 for more information regarding the response procedures 
and response criteria. 
Note that pseudoprogression or initial progression followed by clinical benefit/response may 
occur in patients treated with immune-modulating agents; therefore, treatment past progression 
may be considered if the Investigator and Sponsor agree and the patient is otherwise clinically 
stable and believed to be deriving clinical benefit. Patients who remain on trial past initial 
radiologic progression should have repeat imaging within 4 to 8 weeks.  
6.3.1. 
Response Evaluation Criteria  
PCWG3 criteria will be applied at the time points specified in the Schedules of Assessments 
(Table 2). Assessment of response will be evaluated by computed tomography or magnetic 
resonance imaging of chest/abdomen/pelvis and bone scan every 12 weeks. PSA assessment will 
be performed every cycle. Patients should continue past PSA progression until clear radiologic 
progression or clinical progression (eg, symptomatic or physical deterioration in the absence of 


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radiographic progression that meets PCWG3 criteria). If osseous disease is present at Baseline, 
disease assessment will follow the 2+2 rule to discriminate between flare and true progressive 
disease in bone lesions. The Screening bone scan will be used as the Baseline scan. Patients will 
be permitted to continue on study drug past progression if the Investigator feels the patient is 
otherwise experiencing clinical benefit and Sponsor agrees (see Section 6.3). However, if a 
repeat scan 4 to 8 weeks after initial progressive disease confirms additional progression per 
PCWG3 criteria, the patient should discontinue study drug(s). 
6.4. 
Safety Follow-up Visit 
All patients will have a Safety Follow-up visit at 30 days after the last dose of SRF617, 30 days 
after the last dose of etrumadenant, or 90 days (+ 7 days) after the last dose of zimberelimab 
(30 days after the last dose of zimberelimab if the patient initiates a new anticancer therapy), 
whichever is later. If possible, this visit should occur before the initiation of any subsequent 
anticancer therapy. Patients continuing to experience toxicity at this point after the 
discontinuation of treatment will continue to be followed at least monthly by phone/telehealth or 
in-person visit until resolution or determination in the clinical judgment of the Investigator that 
no further improvement is expected.  
6.5. 
Long-term Follow-up for Safety 
SAEs will be reported through 30 days after the last dose of SRF617, 30 days after the last dose 
of etrumadenant, or 90 days after the last dose of zimberelimab (30 days after the last dose of 
zimberelimab if the patient initiates new anticancer therapy), whichever is later. Pregnancy 
events in female partners of male trial participants will be followed for 30 days after the last dose 
of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last dose of 
zimberelimab, whichever is later. Long-term follow-up reporting may be conducted in person or 
by phone. 
6.6. 
Concomitant Medications or Procedures 
6.6.1. 
Transfusion Support (Prophylaxis or Supportive Care)  
Blood cell transfusion (packed RBCs or platelets) are permitted as clinically indicated. 
Transfusions are also permitted to meet hemoglobin and platelet inclusion criteria. However, the 
patient must have a stable hemoglobin level and platelet count for ≥ 2 weeks prior to dosing 
without transfusion. 
6.6.2. 
Prohibited Medications 
During the study treatment period, the following medications are prohibited: 
• Any additional anticancer therapy. 
• Other investigational agents. 
• Systemic immunostimulatory agents (including but not limited to IFNs and IL-2). 
• Systemic immunosuppressive medications (eg, cyclophosphamide, azathioprine, 
methotrexate, thalidomide, and antitumor necrosis factor-α agents), including 


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systemic corticosteroids administered at > 10 mg/day prednisone or equivalent on a 
long-term basis are prohibited.  
− Acute, low dose (≤ 10 mg/day prednisone or equivalent) systemic 
immunosuppressant medications for management of adverse events or 
premedication are allowed after Medical Monitor approval has been obtained.  
− Inhaled steroids for the management of asthma/chronic obstructive pulmonary 
disease are permitted. 
• If there is a clinical indication for any medication or vaccination specifically 
prohibited during the trial, discontinuation from trial therapy may be required. The 
Investigator should discuss any questions regarding this with the Medical Monitor. 
− Exception: The Sponsor is supportive of patients receiving a Health Authority 
approved COVID-19 vaccine if they have no known contraindications to the 
vaccination. If administered, the name of the vaccine, the dose, and the dates 
administered should be documented in the medical records as well as the 
concomitant medication section of the eCRF. Investigators should have an 
informed risk/benefit discussion with the patient in making the decision to receive 
the vaccine and monitor for toxicity as there could be unknown risks of (1) 
heightened immune response and thus toxicity or (2) diminished immune 
response to either the study treatment, the vaccine, or both. If a trial patient 
decides to pursue an approved COVID-19 vaccination, the Sponsor recommends 
scheduling vaccination such that the full vaccination course occurs at least 
2 weeks before C1D1, when possible.  
• Given potential interactions with etrumadenant, co-administration of the following 
medications are prohibited: 
− BCRP substrates with a narrow therapeutic window, administered orally (eg, 
prazosin, rosuvastatin). 
− P-gp substrates with a narrow therapeutic window, administered orally (eg, 
digoxin). 
− Strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, 
and St. John’s Wort) and strong CYP3A4 inhibitors (eg, clarithromycin, 
grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and 
voriconazole). 
− Refer to Appendix 1 and the following for more examples of relevant substrates, 
inhibitors, and inducers with the potential for drug-drug interactions with 
etrumadenant: https://www.fda.gov/drugs/drug-interactions-labeling/drug-
development-and-drug-interactions-table-substrates-inhibitors-and-inducers. 
6.6.3. 
Other Concomitant Therapies or Procedures 
• Radiation therapy to a symptomatic or progressing solitary lesion including the brain may 
be allowed at the Sponsor’s discretion and if the Investigator feels the patient is deriving 
clinical benefit/disease control in the other disease sites. 


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• Any other medication that is considered necessary for the patient’s welfare, including 
antimicrobial prophylaxis and growth factor support, and that is not expected to interfere 
with the evaluation of study drug may be given at the discretion of the Investigator. 
• Supportive care medicines (eg, bisphosphonates or RANK ligand inhibitors) are allowed 
on trial.  
• Patients may receive a COVID-19 vaccination. Because COVID-19 vaccines are reported 
to have side effects similar to those of an infusion reaction, the vaccination should take 
place at a different place and time from any trial infusion. For vaccines requiring 2 doses, 
both doses should be administered in this fashion. For any patient presenting to clinic or 
emergency department with symptoms consistent with COVID-19 infection70, testing for 
the presence of the novel coronavirus is recommended, as well as isolation and 
quarantine following institutional and local health authority guidance71(for experience 
and recommendations specific to oncology clinics). AEs or treatment discontinuation 
suspected to be attributable to infection with COVID-19 should be indicated as such on 
the relevant case report forms. 
6.6.4. 
Contraception and Pregnancy 
The effects of the study treatment on conception, pregnancy, and lactation are unknown. 
Male patients with female partners of reproductive potential are required to use highly effective 
contraceptive measures from the first dose of study treatment until 30 days after the last dose of 
SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last dose of 
zimberelimab, whichever is later.  
• A man is considered fertile after puberty unless permanently sterile by bilateral 
orchiectomy. 
• A female partner of a male patient is considered fertile following menarche and until 
becoming post-menopausal unless permanently sterile. 
− Permanent sterilization methods include hysterectomy, bilateral salpingectomy, 
and bilateral oophorectomy. 
− A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle-stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a post-menopausal state in women 
not using hormonal contraception or hormonal replacement therapy. However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient. 
Highly effective contraception is defined as use of one or more methods that result in a low 
failure rate (ie, < 1%). Highly effective contraceptive measures include: 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: oral, intravaginal, transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
oral, injectable, implantable 


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• Intrauterine device  
• Intrauterine hormone-releasing system in combination with a barrier method 
(preferably male condom) 
• Surgical sterilization 
− Male patient is vasectomized (with documented medical confirmation of surgical 
success) and is the sole sexual partner of a female with reproductive potential 
− Female partner of the male patient has undergone bilateral tubal ligation 
• Complete sexual abstinence defined as refraining from heterosexual intercourse 
during the entire period of risk associated with study treatment. The reliability of 
sexual abstinence needs to be evaluated in relation to the duration of the clinical trial 
and the preferred and usual lifestyle of the patient 
To ensure proper birth control, male patients, when having sexual intercourse with a female of 
reproductive potential, should use an efficient barrier contraceptive (condom plus spermicide); 
the respective partner should also use an additional efficient contraceptive method (eg, oral pills, 
intrauterine device, or diaphragm, and spermicide). 
Patients should not donate sperm for 4 months after the last dose of any study drug. 
 


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7. 
STUDY DRUG MATERIALS AND MANAGEMENT 
On visit days where study drug is administered in the clinic, dosing will be performed in a 
monitored setting in which there is immediate access to trained personnel and adequate 
equipment and medicine to manage potentially serious reactions.  
7.1. 
SRF617 
7.1.1. 
Description of SRF617 
SRF617 drug product is a sterile filtered liquid, aseptically filled into a single-use stoppered 
glass vial and sealed with a flip-off seal. SRF617 drug product contains at least 2.0 mL at a target 
concentration of 50 mg/mL in 10 mM histidine, 280 nM sucrose, and 0.02% polysorbate 20, pH 
6.0. All lots of drug product are tested to ensure product identity, strength, quality, purity, and 
potency. For IV infusion, the drug product will be diluted into normal saline (0.9%, Sodium 
Chloride Injection, US Pharmacopeia) for injection as diluent. Additional details on the 
preparation and administration of SRF617 drug product will be provided to the Investigator in 
the Pharmacy Manual. 
7.1.2. 
SRF617 Dosage 
Patients will receive SRF617 1400 mg IV q2 weeks on Days 1 and 15 of a 28-day cycle. SRF617 
is administered as an IV infusion supplied by the Sponsor.  
Dose reductions and discontinuations for SRF617 in individual patients may be made based on 
the clinical judgment of the Investigator with notification to the Medical Monitor/Sponsor 
(see Section 7.4).  
7.1.3. 
SRF617 Administration 
SRF617 will be administered as an IV infusion. SRF617 infusion should be administered under 
the supervision of a physician, or other trial personnel, experienced in the use of IV agents. The 
suggested infusion duration range is approximately 30 to 60 minutes. The timing of SRF617 
administration relative to etrumadenant and zimberelimab is shown in Table 5. 


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Table 5: 
Timing of Administration of Study Drug on Infusion Days in Trial 
SRF617-201 
Cycle/Day 
Order/Timing of study drug administrationa 
Day 1 of each 
cycleb 
• 
SRF617 will be administered first 
• 
Etrumadenant will be taken orally after at least a 30-minute observation 
period that begins at the end of the SRF617 infusion 
• 
Zimberelimab will be administered at least 30 minutes after the patient 
has taken etrumadenant  
Day 15 of each 
cycleb 
• 
SRF617 will be administered first 
• 
Etrumadenant will be taken orally after at least a 30-minute observation 
period that begins at the end of the SRF617 infusion 
a 
The timing and order of administration of study drug may be changed at the direction of the trial Safety Review 
Committee. 
b 
On Day 1 and Day 15 infusion visits, patients will hold etrumadenant administration until directed by trial 
personnel.  
Missed doses of SRF617 or zimberelimab (more than ± 3 days) should not be made up; rather, 
follow the schedule for the next biweekly dose. There should be a minimum of 11 days between 
SRF617 infusions and between zimberelimab infusions. The ± 3-day window may be used one 
time per patient during the study treatment period without contacting the Sponsor. Please contact 
the Sponsor if a second ± 3-day window is needed. 
Please refer to the Pharmacy Manual for detailed administration instructions.  
7.1.4. 
SRF617 Storage 
SRF617 is supplied in vials for single use. Each vial contains 100 mg of SRF617 for IV infusion. 
The drug product vials should always be stored in the container provided to the pharmacy and 
should be stored at -20 °C ± 5 ℃ (-13 °F to 5 °F) protected from light. Caution is required when 
handling SRF617. Pharmacists should follow standard procedures for handling investigational 
drugs, including avoidance of eye or skin contact with the drug product. If there is exposure to 
the drug product, the individual should treat for physical exposure (skin washing) or inhalation 
(move to fresh air, as necessary) and, if needed, seek medical advice. During the preparation of 
SRF617, drug product is diluted in normal saline (0.9% Sodium Chloride for Injection, United 
States Pharmacopeia) as diluent. Once diluted, SRF617 should be stored at 2 °C to 8 °C or at 
room temperature until infusion and administered within 4 hours. 
7.1.5. 
SRF617 Preinfusion Medications 
For the first administration of SRF617 (C1D1), no preinfusion medication is required. If a 
Grade 1 or higher infusion-related AE is recorded at any dose, the following premedications 
should be administered for all subsequent doses for that patient: 
• Antipyretics (oral acetaminophen 650-1000 mg) 
• Antihistamine (oral or IV diphenhydramine 25-50 mg or equivalent) 


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Patients with a Grade 2 or higher infusion reaction should also be premedicated with a 
glucocorticoid (IV dexamethasone 20 mg or methylprednisolone 80 mg) for all subsequent 
infusions. 
7.1.6. 
SRF617 Postinfusion Medications 
No specific postinfusion medications are required for SRF617.  
7.1.7. 
SRF617 Treatment Continuation 
Patients will remain on study treatment until disease progression, unacceptable toxicity, or the 
completion of approximately 2 years of study treatment. Patients may remain on study treatment 
longer than 2 years with agreement from the trial Investigator and Sponsor. 
7.2. 
Etrumadenant 
7.2.1. 
Etrumadenant Dosage 
Etrumadenant will be taken orally at a daily dose of 150 mg. Enough etrumadenant bottles 
should be dispensed to cover patient dosing through the next visit. When more than 1 bottle of 
etrumadenant is dispensed, patients should be instructed to open 1 bottle and consume all 
contents before opening another bottle. To assess compliance with self-administration of 
etrumadenant, patients will be required to record the time and date they took each dose in a drug 
diary; missed doses will also be recorded. Patients will be instructed to bring all unused doses of 
etrumadenant and their drug diary to the clinic at specified visits for assessments of compliance. 
See Table 9 for information about possible dose modifications of etrumadenant to manage drug-
related toxicities. 
7.2.2. 
Etrumadenant Administration 
Etrumadenant must be taken with a full cup or glass of non-carbonated room temperature water. 
All capsules for the etrumadenant dose should be taken within minutes of each other. 
Etrumadenant should be taken daily at approximately the same time each day. Patients should 
only take the prescribed dose of etrumadenant once per day. If the patient forgets to take 
etrumadenant at the scheduled time, they should take the dose as soon as they remember. 
However, if the dose is not taken by 9 PM (21:00) that same day, it should be documented as a 
“missed” dose in the dosing diary and the patient should resume dosing the following day at the 
planned dose time. 
Details about the timing of etrumadenant administration on infusion days are provided in 
Table 5. 
Formulation information for etrumadenant may be found in the etrumadenant Investigator 
Brochure. Additional information on the administration, distribution, storage, preparation, 
handling, and destruction of etrumadenant is described in the Pharmacy Manual. 


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7.3. 
Zimberelimab 
7.3.1. 
Zimberelimab Dosage 
Patients will receive zimberelimab 480 mg IV q4 weeks on Day 1 of a 28-day cycle. 
Zimberelimab is administered as an IV infusion supplied by the Sponsor.  
There will be no dose modifications for zimberelimab in this trial. See Table 9 for additional 
information about management of drug-related toxicities with zimberelimab. 
7.3.2. 
Zimberelimab Administration 
Details about the timing of zimberelimab administration are provided in Table 5. 
To reduce the risk of infusion reaction, patients may receive acetaminophen with or without an 
antihistamine or other standard therapy according to local guidelines as pre-medication prior to 
an infusion. 
Formulation information for zimberelimab may be found in the zimberelimab Investigator 
Brochure. Additional information on the administration, distribution, storage, preparation, 
handling, and destruction of zimberelimab is described in the Pharmacy Manual. 
7.4. 
Dose Holds, Modifications, and Discontinuations 
Patients will be monitored continuously for toxicity while on study drug. Toxicity severity will 
be assessed using the NCI-CTCAE version 5.0 or higher. Every effort should be made to 
administer the study drug according to the planned dose and schedule; however, in the event of 
significant treatment-related toxicity, administration of study drug may need to be adjusted as 
described below. 
Holding of 1 agent and not the other agents is appropriate if, in the opinion of the Investigator, 
the toxicity is clearly related to one of the study drugs. Appropriate documentation is required 
regarding the drug(s) to which the Investigator is attributing the AE. If, in the opinion of the 
Investigator, the toxicity is related to the combination of all 3 study drugs, then all 3 drugs 
should be held. 
If all 3 drugs have been withheld for > 56 days, then all study treatment should be discontinued. 
Patients who discontinue any study drug(s) but are continuing to derive clinical benefit from any 
of the others may continue treatment at the discretion of the Investigator and Sponsor.  
7.4.1.1. 
SRF617 
If in the opinion of the Investigator, the patient experiences any of the toxicities outlined in 
Table 6 that are not clearly related to disease progression, intercurrent illness, or concomitant 
medications, then SRF617 dose(s) will be held until recovery of the toxicity to Grade ≤ 1 or to 
the patient’s previous Baseline. Appropriate follow-up assessments should be done until 
adequate recovery occurs as assessed by the Investigator.  


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Table 6: 
Hematologic Toxicities Leading to Dose Hold of SRF617  
Toxicity 
Recommended Dose Delay or Reduction 
Neutropenia 
Grade 3 (ANC < 1000/µL; 1 x 109/L) with a 
single temperature of > 38.3°C (101°F) or a 
sustained temperature of ≥ 38°C (100.4 °F) for 
> 1 hour 
Hold until toxicity recovers to Baseline and then resume at 
reduced dose. If Grade ≥ 3 recurs, permanently discontinue. 
Grade 4 (ANC < 500/µL; < 0.5 × 109/L) 
persisting for ≥ 7 days, and/or complicated by 
infection 
Permanently discontinue. 
Grade 4 life-threatening consequences; urgent 
intervention indicated 
Permanently discontinue. 
Platelets 
Grade 3 (platelets < 50,000-25,000/µL; 
< 50.0-25.0 × 109/L) with associated clinically 
significant bleeding 
Permanently discontinue. 
Grade 4 (platelets < 25,000/µL; < 25.0 × 109/L) 
of any duration bleeding 
Permanently discontinue. 
Anemia 
Grade 4 anemia defined as life-threatening 
consequences; urgent intervention indicated 
(any duration) 
Permanently discontinue. 
All other hematologic toxicity 
Intolerable or recurrent Grade 2 
Hold until resolves to baseline and resume at reduced dose. 
Grade 3 
Hold until resolves to baseline and resume at reduced dose. 
Recurrent Grade 3 or 4 
Permanently discontinue. 
Grade 4 not detailed above 
Permanently discontinue. 
Abbreviation: ANC = absolute neutrophil count. 
Steroids may be used to manage severe (Grade ≥ 3) hematologic toxicity if thought to be 
immune-related.  All attempts should be made to rule out other causes such as metastases, sepsis, 
and/or infection. Relevant diagnostic studies such as peripheral blood smear, reticulocyte count, 
lactate dehydrogenase, haptoglobin, bone marrow biopsy, or Coomb’s test, etc., should be 
considered to confirm the diagnosis. The AE should be reported to the Sponsor regardless of 
etiology. 
In the unlikely event of severe bone marrow suppression, a bone marrow biopsy should be 
performed, if clinically feasible, to assist in determining causality. 
 


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Nonhematologic toxicities that occur during treatment with SRF617 that are not clearly related to 
disease progression, intercurrent illness, or concomitant medications should be managed 
according to the guidelines in Table 7. 


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Table 7: 
Nonhematologic Toxicities Leading to Dose Hold, Modification, or 
Discontinuation of SRF617  
Toxicity 
Recommended dose delay or reduction 
Immune-mediated AEs 
Grade 2 or Grade 3 immune-
mediated AEs 
Hold SRF617 until resolves to Grade ≤ 1 and resume with dose 
reduced by 1 level. 
Grade 4 immune-mediated AEs 
Permanently discontinue SRF617. 
Hepatotoxicity 
> 2 × ULN bilirubin AND 
Grade ≥ 2 ALT/AST (> 3 × ULN) 
in patients who enroll with 
Grade ≤ 1 ALT/AST 
 
OR 
 
> 2 × ULN bilirubin AND doubling 
of ALT/AST in patients who enroll 
with Grade 2 ALT/AST 
In the absence of biliary obstruction or other cause responsible 
for the concurrent elevation, permanently discontinue SRF617. 
Grade 4 ALT/AST elevation 
OR 
Grade 4 bilirubin elevation 
Permanently discontinue SRF617. 
Metabolic 
Grade 3 electrolyte disturbance 
Hold SRF617 until resolves to Grade ≤ 1 or Baseline and 
resume with same dose (first occurrence) or with dose reduced 
by 1 level after resolution (second occurrence). 
Grade 4 electrolyte disturbance 
Hold SRF617 until resolves to Grade ≤ 1 or Baseline and 
resume with same dose if resolves in ≤ 72 hours; permanently 
discontinue if resolution takes > 72 hours. 
Gastrointestinal  
Grade 3 vomiting, diarrhea, or 
nausea  
Hold SRF617 until resolves to Grade ≤ 1 or Baseline and 
resume with same dose if resolves in ≤ 72 hours with supportive 
care. If it lasts > 72 hours despite optimal supportive care, 
resume with dose reduced by 1 level. 
Patients must be contacted by the Investigator or trial nurse 
daily until it is clear that the problem has resolved or requires 
additional support (eg, hospitalization). 
Grade 4 vomiting or diarrhea 
Permanently discontinue SRF617. 


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Toxicity 
Recommended dose delay or reduction 
Other nonhematologic toxicities 
Grade 2 or Grade 3 AEs that, in the 
opinion of the Investigator, require 
dose reduction  
Hold SRF617 until resolves to Grade ≤ 1 or Baseline and 
resume with dose reduced by 1 level. 
Evaluate at least once weekly after the initial identification of 
the toxicity until its resolution or stabilization. 
Grade 4a AEs that, in the opinion of 
the Investigator, require dose 
reduction 
Permanently discontinue SRF617. 
Other  
 
Treatment delays of > 56 days due 
to drug–related toxicities 
Permanently discontinue SRF617. 
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
ULN = upper limit of normal. 
a Other than laboratory abnormalities that Investigator deems clinically insignificant and that last ≤ 72 hours. 
For toxicities that also meet the stopping rule criteria for safety (see Section 4.6), after the first 
occurrence of the toxicity, the Investigator may resume SRF617 treatment at 1 dose level lower 
upon recovery of the toxicity to Grade ≤ 1 or Baseline value (Table 8). For toxicities that do not 
meet the stopping rule criteria for safety, the Investigator may resume SRF617 treatment at the 
same dose level upon recovery of the toxicity to Grade ≤ 1 or Baseline value. Any patient who 
requires more than 2 dose level reductions or requires holding of SRF617 for more than 56 days 
will be permanently discontinued from the study drug. 
 
Table 8: 
Recommended Dose Reductions for SRF617 
 
Initial dose 
First dose reduction 
Second dose reduction 
SRF617 
1400 mg 
700 mg 
350 mg 
 
Patients who have a dose reduction because of a toxicity may be eligible for a dose increase back 
to the dose level before the reduction if the following criteria are met and approved by the 
Sponsor: 
• Patient has tolerated the lower dose level for > 1 treatment cycle 
• Patient has recovered to Baseline levels from the toxicity that caused the dose 
reduction 
Patients who have a dose reduction because of a Grade 4 nonhematologic AE may not 
re-escalate the dose after a dose reduction. 


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Infusion-Related Reactions 
For infusion reactions of any grade/severity, immediately interrupt the SRF617 infusion and 
manage symptoms. Management of infusion reactions may require reduction in the rate of 
infusion or treatment discontinuation of SRF617, as outlined below:  
• Grade 1 to 2 (mild or moderate): Once reaction symptoms resolve, resume the 
infusion at no more than half the rate at which the reaction occurred. If the patient 
does not experience any further reaction symptoms, infusion rate escalation may 
resume in increments and at intervals clinically appropriate up to the maximum rate 
of 100 mL/h. 
• Grade 3 (severe): Once reaction symptoms resolve, consider restarting the infusion at 
no more than half the rate at which the reaction occurred. Repeat the procedure above 
in the event of recurrence of Grade 3 symptoms. Permanently discontinue SRF617 
upon the third occurrence of a Grade 3 or greater infusion reaction. 
• Grade 4 (life-threatening): Permanently discontinue SRF617 treatment. 
No dose reductions of SRF617 for infusion-related reactions are recommended.  
For any patient who has a Grade ≥ 2 infusion reaction with SRF617, steroidal premedication 
should be used for all subsequent infusions (see Section 7.1.5). 
7.4.1.2. 
Etrumadenant and Zimberelimab 
Dose holds of etrumadenant or zimberelimab are allowed throughout the trial for no more than 
56 days. If either drug has been withheld for more than 56 days, then that drug should be 
permanently discontinued.  
For management of drug-related toxicities, the dose of etrumadenant may be reduced up to 
2 times as outline in Table 9. If further dose reduction below 75 mg is indicated, etrumadenant 
should be discontinued. After dose reduction, the dose may be escalated during subsequent 
administrations at the Investigator’s discretion with Medical Monitor approval. There will be no 
dose reductions for zimberelimab in this trial. 
 
Table 9: 
Recommended Dose Reductions for Etrumadenant 
 
Initial dose 
First dose reduction 
Second dose reduction 
Etrumadenant 
150 mg 
100 mg 
75 mg 
Zimberelimab 
480 mg 
N/A 
N/A 
 
Guidelines for the management of patients who experience specific AEs are provided in 
Table 10. For AEs for which management guidelines are not provided, patients should be 
managed, and study treatment should be modified as deemed appropriate by the Investigator 
according to best medical practice.


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Table 10: 
Guidelines for Management of Patients who Experience Adverse Events Considered to be Related to 
Etrumadenant and/or Zimberelimab 
Event 
Severity 
Etrumadenant action to be taken 
Zimberelimab action to be taken 
Infusion-related 
reaction 
(including 
hypersensitivity 
and anaphylaxis) 
Grade 1-2 
Continue etrumadenant at the same dose level. Institute 
symptom-directed supportive care according to institutional 
guidelines. 
Refer to the NCCN or institutional guidelines for the 
Management of Immune CPI-Related Toxicities for 
symptom-directed supportive care. Zimberelimab, if 
interrupted, may be withheld for up to 56 days after event 
onset. 
Grade 3-4 
Consider etrumadenant dose modification as clinically 
indicated, otherwise continue at the same dose. 
Institute symptom-directed supportive care according to 
institutional guidelines. 
Consider zimberelimab treatment interruption or 
permanent discontinuation as clinically indicated. Refer to 
the NCCN or institutional guidelines for the Management 
of Immune CPI Related Toxicities for symptom-directed 
supportive care. 
Dermatologic 
toxicity 
(including but not 
limited to rash, 
maculopapular 
rash, and pruritis) 
Grade 1 
Continue etrumadenant at the same dose level. Immediately 
institute supportive care measures for symptomatic relief. 
Refer to the NCCN or institutional guidelines for the 
Management of Immune CPI-Related Toxicities for 
symptom-directed supportive care. Zimberelimab, if 
interrupted, may be withheld for up to 56 days after event 
onset. 
Grade 2 
Consider etrumadenant dose modification as clinically 
indicated; otherwise continue at the same dose. 
For suspected etrumadenant-related events: 
• 
Immediately institute supportive measures. 
• 
If the event does not resolve to Grade 1 or better within 
7 days, consider dose interruption. If event resolves to 
Grade 1 or better, resume etrumadenant at the same 
dose or with a one-level dose reduction (Table 9). 
• 
Etrumadenant dose re-escalation is permitted at the 
Investigator’s discretion. 
Grade 3 
Withhold etrumadenant for at least 7 days until toxicity 
resolves to Grade 1 or better. 
For suspected etrumadenant-related events: 
• 
Immediately institute supportive measures. 
• 
If event resolves to Grade 1 or better within 56 days, 
resume etrumadenant with a one-level dose reduction 
(Table 9).a If not, permanently discontinue 
etrumadenant and contact Medical Monitor. 


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Event 
Severity 
Etrumadenant action to be taken 
Zimberelimab action to be taken 
• 
Etrumadenant dose re-escalation is permitted at the 
Investigator’s discretion. 
Grade 4 
Permanently discontinue etrumadenant and contact Medical 
Monitor 
Permanently discontinue zimberelimab and contact 
Medical Monitor 
Hepatic toxicity 
(including 
elevations in 
transaminases 
and/or bilirubin) 
Grade 1-2 
ALT/AST 
≤ 5 × ULN 
Continue etrumadenant at the same dose level at the 
Investigator’s discretion. Monitor LFTs more frequently 
until return to < 3 × ULN or Baseline. 
Refer to the NCCN or institutional guidelines for the 
Management of Immune CPI-Related Toxicities for 
symptom-directed supportive care. Zimberelimab, if 
interrupted, may be withheld for up to 56 days after event 
onset. 
Grade 3 
ALT/AST 
> 5 × ULN 
but ≤ 20 × 
ULN 
For suspected non-immune-mediated transaminase elevations: 
• 
Withhold etrumadenant and zimberelimab for up to 56 days. 
• 
Monitor LFTs at least weekly for a minimum of 4 weeks until transaminases return to < 3 × ULN or Baseline. 
• 
Consider patient referral to GI specialist for evaluation and liver biopsy to establish etiology of hepatic injury. 
• 
If event resolves to Grade 1 or better within 56 days, resume etrumadenant with a one-level dose reduction (Table 9) 
and resume zimberelimab.a If not, permanently discontinue etrumadenant and zimberelimab and contact Medical 
Monitor. 
For suspected immune-mediated transaminase elevations: 
• 
Permanently discontinue zimberelimab and contact Medical Monitor. 
• 
Withhold etrumadenant for up to 56 days. 
• 
Consider patient referral to GI specialist for evaluation and liver biopsy to establish etiology of hepatic injury. 
• 
Initiate treatment with corticosteroids equivalent to 1-2 mg/kg/day oral prednisone. If event does not improve within 
48 hours after initiating corticosteroids, consider adding an immunosuppressive agent. 
• 
If event resolves to Grade 1 or better within 56 days, taper corticosteroids over ≥ 1 month and resume etrumadenant 
with a one-level dose reduction (Table 9).a If not, permanently discontinue etrumadenant and contact Medical 
Monitor. 
Grade 4 
ALT/AST 
> 20 × 
ULN 
Permanently discontinue etrumadenant and contact Medical 
Monitor. For suspected immune-mediated transaminase 
elevations, follow Grade 3 management guidelines. 
Permanently discontinue zimberelimab and contact 
Medical Monitor. For suspected immune-mediated 
transaminase elevations, follow Grade 3 management 
guidelines. 
ALT/AST 
> 3 × ULN 
with 
• 
Permanently discontinue etrumadenant and zimberelimab and contact Medical Monitor. 
• 
Monitor liver function at least weekly until values return to Baseline. 


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Event 
Severity 
Etrumadenant action to be taken 
Zimberelimab action to be taken 
concurrent 
bilirubin > 
2 × ULN 
• 
Investigate causes for elevated bilirubin and initiate treatment according to institutional guidelines. 
• 
Exception: Patients with Gilbert syndrome who develop elevated transaminases should be managed as per the above 
outlined recommendations for the respective observed elevation of ALT and/or AST. 
Fatigue 
Grade 1-2 
Continue etrumadenant at the same dose level. Institute 
symptom-directed supportive care according to institutional 
guidelines. 
Refer to the NCCN or institutional guidelines for the 
Management of Immune CPI-Related Toxicities for 
symptom-directed supportive care. Zimberelimab, if 
interrupted, may be withheld for up to 56 days after event 
onset. 
Grade 3-4 
Consider etrumadenant dose modification as clinically 
indicated, otherwise continue at the same dose.a 
Institute symptom-directed supportive care according to 
institutional guidelines. 
Consider zimberelimab treatment interruption or 
permanent discontinuation as clinically indicated. Refer to 
the NCCN or institutional guidelines for the Management 
of Immune CPI Related Toxicities for symptom-directed 
supportive care. 
Gastrointestinal 
toxicity 
(including but not 
limited to diarrhea 
and colitis) 
Grade 1 
• 
Continue etrumadenant at the same dose level. 
• 
Initiate symptomatic treatment and monitor closely. 
• 
Endoscopy is recommended if symptoms persist 
> 7 days. 
Refer to the NCCN or institutional guidelines for the 
Management of Immune CPI-Related Toxicities for 
symptom-directed supportive care. Zimberelimab, if 
interrupted, may be withheld for up to 56 days after event 
onset. 
Grade 2 
• 
Consider etrumadenant dose modification as clinically 
indicated, otherwise continue at the same dose. 
• 
Initiate symptomatic treatment. 
• 
Referral to GI specialist is recommended. 
• 
For recurrent events or events that persist > 5 days, 
initiate treatment with corticosteroids equivalent to 
1-2 mg/kg/day oral prednisone. 
• 
1st occurrence: If etrumadenant was withheld and 
event resolves to Grade 1 or better within 56 days, 
resume etrumadenant at the same dose level. 
• 
Recurrent or persistent events: If etrumadenant was 
withheld and event resolves to Grade 1 or better within 
56 days, resume etrumadenant with a one-level dose 
reduction (Table 9).a If not, permanently discontinue 
etrumadenant and contact Medical Monitor. 


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Event 
Severity 
Etrumadenant action to be taken 
Zimberelimab action to be taken 
• 
Etrumadenant dose re-escalation is permitted at the 
Investigator’s discretion. 
Grade 3 
Withhold etrumadenant for up to 56 days after event onset. 
For suspected immune-mediated events (including 
colitis): 
• 
Refer patient to GI specialist for evaluation and 
confirmatory biopsy. 
• 
Initiate treatment with corticosteroids equivalent to 
1-2 mg/kg/day IV methylprednisolone and convert to 
1-2 mg/kg/day oral prednisone or equivalent upon 
improvement. 
• 
Follow guidance for Grade 2 recurrent or persistent 
events. 
Grade 4 
Permanently discontinue etrumadenant and zimberelimab and contact Medical Monitor. 
• 
Refer patient to GI specialist for evaluation and confirmation biopsy. 
• 
Initiate treatment with corticosteroids equivalent to 1-2 mg/kg/day IV methylprednisolone and convert to 
1-2 mg/kg/day oral prednisone or equivalent upon improvement. If event does not improve within 48 hours after 
initiating corticosteroids, consider adding an immunosuppressive agent. 
• 
If event resolves to Grade 1 or better, taper corticosteroids over ≥ 1 month. 
Etrumadenant-
related toxicities 
not described 
above 
Grade 1-2 
Consider etrumadenant dose modification as clinically 
indicated, otherwise continue at the same dose. Institute 
symptom directed supportive care according to institutional 
guidelines. 
Continue zimberelimab. 
Grade 3 
• 
Withhold etrumadenant for up to 56 days after event 
onset.  
• 
If event resolves to Grade 1 or better within 56 days 
resume etrumadenant with a one level dose reduction.a 
If not, permanently discontinue etrumadenant and 
contact Medical Monitor. 
• 
Etrumadenant dose re-escalation is permitted at the 
Investigator’s discretion. 
Continue zimberelimab at the Investigator’s discretion. 


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Event 
Severity 
Etrumadenant action to be taken 
Zimberelimab action to be taken 
Grade 4 
Permanently discontinue etrumadenant and contact Medical 
Monitor. 
Withhold zimberelimab for up to 56 days after event 
onset. If event improves and Medical Monitor agrees that 
zimberelimab should be continued, resume zimberelimab; 
otherwise, permanently discontinue zimberelimab. 
Zimberelimab-
related toxicities 
not described 
above 
Grade 1-2 
Continue etrumadenant at the same dose level. 
Refer to the NCCN or institutional guidelines for the 
Management of Immune CPI-Related Toxicities for 
symptom-directed supportive care. Zimberelimab, if 
interrupted, may be withheld for up to 56 days after event 
onset. 
Grade 3 
• 
Consider etrumadenant dose modification as clinically 
indicated, otherwise continue at the same dose. 
• 
Initiate symptomatic treatment. 
• 
If etrumadenant was withheld and event resolves to 
Grade 1 or better within 56 days, resume etrumadenant 
with a one-level dose reduction.a 
• 
Etrumadenant dose re-escalation is permitted at the 
Investigator’s discretion. 
Refer to the NCCN or institutional guidelines for the 
Management of Immune CPI-Related Toxicities for 
symptom-directed supportive care. Zimberelimab, if 
interrupted, may be withheld for up to 56 days after event 
onset. 
Grade 4 
Permanently discontinue etrumadenant and contact Medical 
Monitor. 
Permanently discontinue zimberelimab and contact 
Medical Monitor. 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPI = checkpoint inhibitor; GI = gastrointestinal; IV = intravenous; 
LFT = liver function test; NCCN = National Comprehensive Cancer Network; ULN = upper limit of normal 
a The dose of etrumadenant can be reduced from 150 mg to 100 mg (ie, one dose level) and then from 100 mg to 75 mg for management of drug-related 
toxicities. Additional dose reductions are not allowed. If a dose reduction is indicated for a patient receiving the 75 mg dose of etrumadenant, then that patient 
should discontinue etrumadenant. 
 


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7.5. 
Drug Accountability 
The Investigator or designee is responsible for taking an inventory of each shipment of study 
drug received and comparing it with the accompanying drug order form. 
All unused study drug will be retained at the site. After full drug accountability and 
reconciliation, the Investigator will dispose of any study drug at the clinical trial site per site 
procedures, or if necessary, all study drug will be returned to the Sponsor, or its designee. 
Disposition of all study drug should be documented, including any study drug that is lost or 
damaged.  
7.6. 
Assignment to Treatment 
All patients will receive open-label study drug at a dose and schedule based on the trial design 
(see Section 4). 


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8. 
SAFETY DATA COLLECTION, RECORDING, AND 
REPORTING 
8.1. 
Adverse Events  
8.1.1. 
Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence associated with the use of a drug, or with 
trial participation, whether or not considered related to study drug.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease temporally associated with the use of the medicinal 
product, whether or not considered related to the medicinal product.  
AEs include worsening of a preexisting medical condition as well as clinically significant changes 
from Baseline laboratory values/conditions. Worsening of the preexisting medical condition (eg, 
diabetes, hypertension) means that it has increased in severity, frequency, and/or duration, and/or 
has an association with a significantly worse outcome. A preexisting condition that has not 
worsened during the trial is not considered an AE. Progression of the cancer under study is not 
considered an adverse event unless it results in hospitalization or death.  
8.1.2. 
Definition of Serious Adverse Event  
An AE or suspected adverse reaction is termed “serious” if according to the Investigator or 
Sponsor, it: 
• Results in death 
• Is life-threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization  
− Elective or preplanned treatment for a preexisting condition that is unrelated to 
the indication under study and has not worsened since signing the ICF (as 
documented as medical history on the eCRF) is not considered an SAE. 
− Scheduled therapy for the target disease of the trial, including admissions for 
transfusion support or convenience, is not considered an SAE. 
• Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions 
• Results in congenital anomaly/birth defect 
• Is considered an important medical event 
− If an AE does not meet one of the serious criteria, but the Investigator or Sponsor 
considers an event to be clinically important, the event could be classified as an 
SAE under the criterion of important medical event. Examples of such medical 
events may include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, or blood dyscrasias or convulsions that do not result 
in inpatient hospitalization. 


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Per NCI-CTCAE version 5.0, if death is due to an AE (eg, Cardiac disorders: Cardiac arrest; 
infection, pulmonary embolism), it should be reported as a Grade 5 event under that System 
Organ Class and Preferred Term. However, if death is due to disease progression but cannot be 
attributed to a specific NCI-CTCAE term associated with Grade 5, the AE should be reported as 
NCI-CTCAE Preferred Term “disease progression” found in the System Organ Class, “General 
disorders and administration site conditions.” Evidence that the death was a manifestation of the 
underlying disease (eg, radiological changes suggesting tumor growth or progression; clinical 
deterioration associated with a disease process) should be submitted. 
8.1.3. 
Definition of an Adverse Event of Special Interest 
AESIs will be collected to evaluate potential class effects for antibodies targeting CD39. AESIs 
for this trial are defined as thromboembolic events, eg, DVT, pulmonary embolism, stroke, 
myocardial infarction.  
8.2. 
Procedures for Recording and Reporting Adverse Events 
8.2.1. 
Recording Adverse Events 
Patients will be instructed to report all AEs and will be asked a general health status question at 
each trial visit. All SAEs occurring in patients will be recorded in the eCRF from the time of 
signing the ICF through the Safety Follow-up visit, 30 days after the last dose of SRF617, 
30 days after the last dose of etrumadenant, or 90 days after the last dose of zimberelimab 
(30 days after the last dose of zimberelimab if the patient starts another anticancer therapy), 
whichever is later. All AEs occurring in treated patients will be recorded in the eCRF from the 
time of first dose through 30 days after the last dose of SRF617, 30 days after the last dose of 
etrumadenant, or 90 days after the last dose of zimberelimab (30 days after the last dose of 
zimberelimab if the patient starts another anticancer therapy), whichever is later. An AE will be 
followed until it is either resolved, has returned to Baseline, or is determined to be a stable or 
chronic condition. All SAEs occurring from the signing of the ICF through 30 days after the last 
dose of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last dose of 
zimberelimab (30 days after the last dose of zimberelimab if the patient starts another anticancer 
therapy), whichever is later, will be processed as outlined in Section 8.2.2.  
At each required visit during the trial, all AEs that have occurred since the previous visit must be 
reviewed by the Investigator. The Investigator must determine if the AE is serious or nonserious.  
The Investigator must assign the following AE attributes: 
• AE diagnosis or syndrome(s) if known 
− If not known at time of the report, record the signs and/or symptoms as AEs and 
provide an updated report with diagnosis when obtained. 
• Dates of onset and resolution 
• Severity as defined per protocol 
• Assessment of relatedness to each study drug 
• Action taken with each study drug as a result of the AE 


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In general, an AE that is the primary cause of subsequent events should be identified by the 
primary cause; eg, for dehydration due to diarrhea, the AE would be diarrhea. However, AEs 
occurring secondary to an initiating event that are separated in time should be recorded as 
independent events; eg, for sepsis secondary to pneumonia, both events should be recorded.  
The signs and symptoms of progressive disease that meet the AE criteria should be reported as 
specific AEs and not as disease progression.  
8.2.1.1. 
Relationship to Study Drug 
The Investigator must assess whether the AE may be related to each study drug or trial-mandated 
procedure, when applicable. The relationship is defined below:  
Relationship assessments that indicate the event is “not drug related”: 
• None: The event is related to an etiology other than the study drug administration (the 
alternative etiology must be documented in the trial patient’s medical record). 
• Remote: The event is unlikely to be related to the study drug and likely to be related 
to factors other than study product. 
Relationship assessments that indicate the event is “drug related”: 
• Possible: There is an association between the event and the administration of study 
drug, and there is a plausible mechanism for the event to be related to the study drug; 
but there may also be alternative etiology, such as characteristics of the patient’s 
clinical status or underlying disease. 
• Probable: There is an association between the event and the administration of study 
drug, there is a plausible mechanism for the event to be related to the study drug, and 
the event could not be reasonably explained by known characteristics of the patient’s 
clinical status or an alternative etiology is not apparent. 
• Definite: There is an association between the event and the administration of study 
drug, there is a plausible mechanism for the event to be related to the study drug, and 
causes other than study drug have been ruled out and/or the event reappeared on 
re-exposure to study drug. 
8.2.1.2. 
Adverse Event Severity 
The Investigator will assess the grade of the AE per the NCI-CTCAE version 5.0 or higher. 
Toxicities that are not specified in NCI-CTCAE will be defined as follows:  
• Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
• Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL) 
• Grade 3: severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL 
• Grade 4: life-threatening consequences; urgent intervention indicated 


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• Grade 5: death related to AE 
Note: It is important to distinguish between SAEs and severe AEs. Severity is a measure of 
intensity, whereas seriousness is classified by the criteria based on the regulatory definitions as 
described in Section 8.1.2 above. 
8.2.1.3. 
Abnormal Laboratory and Electrocardiogram Values 
The Investigator is responsible for reviewing clinical laboratory test and ECG results and 
determining whether an abnormal value in a patient represents a clinically significant change 
from the patient’s Baseline value. In general, abnormal laboratory findings and ECGs without 
clinical significance (based on the Investigator’s judgment) should not be recorded as AEs. In 
general, an abnormal laboratory test and ECG results should be reported as an AE if the 
laboratory result: 
• Requires an adjustment or discontinuation of study drug  
• Requires treatment or adjustment to concomitant medications 
• Is considered to be an AE by the Investigator 
8.2.1.4. 
Medication Errors, Misuse, and Abuse of Study Drug 
Overdose, medication error, misuse, and abuse are defined as follows: 
• Medication error: refers to an unintentional error in dispensing or administration of 
study drug not in accordance with the protocol  
• Off-label use: relates to situations where the study drug is intentionally used for 
medical purpose not in accordance with the protocol 
• Misuse: refers to situations where the study drug is intentionally and inappropriately 
used not in accordance with the protocol 
• Abuse: corresponds to the persistent or sporadic, intentional excessive use of the 
study drug, which is accompanied by harmful physical or psychological effects 
• Occupational exposure: refers to the exposure to the study drug because of one’s 
professional or nonprofessional occupation 
No specific information is available on the treatment of overdose of study drug. In the event of 
overdose, the patient should be observed closely for signs of toxicity. Appropriate supportive 
treatment should be provided if clinically indicated. 
Overdoses, medication errors, abuse, and misuse will be collected as part of investigational 
medicinal product dosing information and/or as protocol violations, as required.  
8.2.2. 
Reporting of Serious Adverse Events and Adverse Events of Special Interest 
An SAE/AESI report form will be completed in the electronic data capture (EDC) system and 
submitted to the Sponsor or designee within 24 hours of the Investigator’s first knowledge of the 
event, even if the experience does not appear to be related to study drug, from the time of signing 
the ICF through 30 days after the last dose of SRF617, 30 days after the last dose of 
etrumadenant, or 90 days after the last dose of zimberelimab (30 days after the last dose of 


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zimberelimab if the patient initiates new anticancer therapy), whichever is later. In the event that 
EDC is unavailable, the SAE/AESI paper report form must be filled out by the Investigator and 
sent via email within 24 hours of awareness of the event to the Clinipace Pharmacovigilance 
Department (safetygroup@clinipace.com), and then the information entered into the EDC once 
available.  
Please refer to the SAE/AESI report form and completion guidelines for more detailed 
instructions.  
The initial SAE/AESI report must be as complete as possible, including details of the current 
illness and SAE/AESI and an assessment of the relationship between the event and study drugs. 
Additional information relating to a previously reported SAE/AESI must also be reported within 
24 hours of the Investigator’s first knowledge of information. The Investigator may also be 
asked, by the Sponsor, to provide clarifications or additional information. 
If the Investigator becomes aware of an SAE/AESI considered related to study drug(s) by the 
Investigator occurring more than 30 days after the last dose of SRF617, 30 days after the last 
dose of etrumadenant, or 90 days after the last dose of zimberelimab, the SAE must be reported 
as described above.  
8.2.2.1. 
Reporting of Serious Adverse Events to Regulatory Authorities, Ethics 
Committee, and Institutional Review Board 
The Sponsor or designee will determine expectedness for each reported SAE based on the 
appropriate reference safety information for the study drug per local requirements. The Sponsor 
or designee shall notify regulatory authorities of serious, unexpected, and related AEs or other 
AEs, per local requirements.  
The Sponsor or designee shall notify the Investigator of serious, related, and unexpected AE(s) 
submitted to the regulatory agencies, per local country requirements.  
The Investigator shall notify the Central Ethics Committees of serious, related, and unexpected 
AE(s), or significant risks to patients, per country requirements. 
The Investigator will notify the appropriate IRB/Local Ethics Committees of serious, related, and 
unexpected AE(s), or significant risks to patients, per local country requirements. The 
Investigator must keep copies of all AE information on file, including correspondence with the 
Sponsor or IRBs/IECs. 
8.2.2.2. 
Reporting Adverse Events of Special Interest 
AESIs for this trial are defined as thromboembolic events, eg, DVT, pulmonary embolism, 
stroke, myocardial infarction. The Investigator should report both serious and nonserious 
thromboembolic events to the Sponsor using the same methods as described for reporting SAEs.  
8.2.3. 
Pregnancy and In Utero Drug Exposure 
Pregnancies occurring in partners of male patients are considered immediately reportable events 
if the pregnancy occurs during the study treatment period through 30 days after the patient’s last 
dose of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last dose of 


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zimberelimab, whichever is later. The Investigator will attempt to collect pregnancy information 
on any male patient’s female partner who becomes pregnant while the male patient is in this trial.  
Please refer to the pregnancy notification form or pregnancy outcome form and associated 
completion guidelines on where and how to submit the forms.  


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9. 
STATISTICAL METHODS 
Details of the statistical methods for this trial will be documented in a statistical analysis plan 
(SAP). The SAP may modify the statistical methods outlined in the protocol; however, any major 
modification will also be reflected in a protocol amendment. 
9.1. 
Sample Size 
This trial will enroll approximately 40 patients. A patient is enrolled in the trial after they have 
provided informed consent and met all trial eligibility criteria.  
A Simon 2-stage design will be implemented. Simon Stage 1 will include a 6-patient Safety 
Lead-in followed by enrollment of an additional 11 patients for a total of 17 patients. At least 1 
radiographic CR/PR or 2 PSA50 responses by PCWG3 criteria out of 17 evaluable patients must 
be observed in order to consider opening Stage 2, which will enroll an additional 23 patients for 
further evaluation of the safety and efficacy of the triplet. The trial will have met its primary 
endpoint if at least 8 patients in total achieve a response. 
The sample size for this triplet combination therapy dose expansion is based on a null hypothesis 
of a 10% composite response rate (PSA50 or CR/PR) with PD-1 blockade alone versus the 
alternate hypothesis that the composite response rate is 30%, with a calculated alpha of 0.040 
and power of 0.93.  
9.2. 
Analysis Sets 
The main analysis sets are defined in this section. Additional analysis sets may be defined in the 
SAP.  
9.2.1. 
Safety Lead-in Evaluable Analysis Set 
The Safety Lead-in Evaluable Analysis Set is defined as the first 6 patients enrolled in the Simon 
Stage 1 who either experienced a Grade ≥ 3 related AE during the first cycle of therapy (D1-28) 
or who completed at least 50% of the prescribed combination therapy doses. The SRC will 
review the aggregate safety data of these 6 patients during Cycle 1 and must clear the trial for 
further enrollment of the remaining 11 patients in Stage 1. The goal of the safety evaluation for 
the triplet is to evaluate for any signal of unexpected or increased toxicities when given together 
that would not be observed with any agent alone. As such, a Grade ≥ 3 toxicity known to be 
associated with any of the 3 study drugs’ established safety profiles would not be considered 
concerning.  
9.2.2. 
Safety Analysis Set 
The Safety Analysis Set is defined as all patients who received any amount of study drug. This 
analysis set will be the primary analysis set for all safety endpoints, excluding safety lead-in 
evaluation. This analysis set will be used to assess the tolerability of SRF617 in combination 
with etrumadenant and zimberelimab. 
9.2.3. 
Response-Evaluable Analysis Set 
The Response-Evaluable Analysis Set is defined as all patients at Baseline who received study 
drug and had at least 1 post-Baseline response assessment or who discontinued the treatment 


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phase because of radiographic or symptomatic disease progression (including death caused by 
disease progression) within 6 weeks (+ 2 week window) of the first dose of study drug. This 
analysis set will be the primary analysis set for the primary efficacy endpoint and other efficacy 
endpoints.  
9.2.4. 
Intent-to-Treat Analysis Set 
The Intent-to-Treat Analysis Set is defined as all enrolled patients who received any amount of 
study drug. 
9.2.5. 
SRF617 Pharmacokinetics Analysis Set 
The PK Analysis Set is defined as all enrolled patients who received at least 1 dose of study drug 
and had at least 1 measurable PK concentration after SRF617 administration. 
9.2.6. 
Biomarker Analysis Set 
The Biomarker Analysis Set is defined as all enrolled patients who received at least 1 dose of 
study drug and had at least 1 adequate pharmacodynamic assessment after SRF617 
administration. 
9.2.7. 
Tumor Biopsy Analysis Set 
The Tumor Biopsy Analysis Set is defined as patients with non-bone metastases amenable to 
biopsy, who consent to optional Baseline (± on therapy) biopsies of the metastatic site, and for 
whom the procedure is deemed safe. 
9.3. 
Background Characteristics 
9.3.1. 
Patient Disposition 
The number and percentage of patients in each trial population, number of cycles completed, 
reason for discontinuing treatment, and reason for discontinuing the trial will be summarized.  
9.3.2. 
Demographics and Baseline Characteristics 
The following demographics and Baseline characteristics will be summarized for the Safety 
Analysis Set: sex, race, age, tumor stage (tumor-node-metastases), ECOG performance status, 
time elapsed since cancer diagnosis, sites of disease at trial entry, and prior anticancer therapies. 
These parameters will be summarized by incidence (n, %). Additional parameters may be 
specified in the SAP.  
9.4. 
Study Drug Exposure and Compliance 
Total number of cycles is defined as the maximum number of treatment cycles that a patient 
receives. Total cumulative dose (mg) is the sum of the actual doses that the patient receives 
across cycles. Total planned dose (mg) is the sum of the planned doses. The total number of 
cycles, total cumulative dose (mg), and total planned dose (mg) will be summarized. 
The study drug exposure will be summarized based on the Safety Analysis Set. 


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9.5. 
Efficacy Analyses 
ORR will be assessed separately by PCWG3 criteria as well as RECIST v1.1. The primary 
response endpoint is defined as the proportion of patients achieving PSA50 and/or radiographic 
objective response of CR/PR measured using PCWG3 criteria. PSA response (PSA50) is defined 
as a confirmed PSA decrease from Baseline of 50% or more based on 2 consecutive assessments 
measured 3 to 4 weeks apart.1 Changes in PSA across the trial period will be described using a 
waterfall plot. Swimmer plots will be used to describe time on trial, including timing and 
incidence of treatment past progression and timing of SAEs or AESIs, and may be used to reflect 
the concept of no longer clinically benefiting. 
For efficacy endpoints derived from progression and/or response status, disease assessments after 
the start of new anticancer therapy will be excluded from consideration. 
The number and percentage of patients with best overall response per PCWG3 criteria and per 
RECIST v1.1 in each of the response categories will be presented. ORR will be estimated by the 
percentage of patients achieving a best overall response of CR or PR. The estimated ORR along 
with the 2-sided 80% and 95% exact CIs will be provided.  
Time-to-event endpoints such as the following will be summarized and estimated via the Kaplan-
Meier method if the number of events is adequate: 
• DoR, defined as the time from the first documented response (PSA50 and/or CR/PR) 
to documented disease progression as determined by applicable disease criteria, or 
documented death due to any cause, whichever occurs first. PSA50 and objective 
responses (CR or PR) will also be assessed individually. 
• DCR, defined as the percentage of patients with CR, PR, or stable disease lasting a 
minimum of 12 weeks 
• PFS, defined as the time from the first treatment on trial with study drug to 
documented disease progression as determined by applicable disease criteria or death 
• Landmark PFS, defined as the percentage of patients who have not developed PFS 
events (ie, death or documented disease progression as determined by applicable 
disease criteria) at 6 months, 12 months, 18 months, and 24 months  
• Time to PSA progression 
• Time to radiologic progression 
Subgroup analyses for efficacy endpoints will be done when possible and will be generally 
descriptive. The following subgroups are prespecified for analysis, based on Baseline 
characteristics: PSA (above or below the median at trial Baseline), age (above or below the 
median at trial Baseline, ≥ 70 years or < 70 years), ECOG performance status (0 or 1), 
distribution of metastatic disease (bone only ± nodal disease, nodal disease only [no bone disease 
present]: pelvic and extrapelvic, visceral [lung, liver, adrenal, CNS] disease [± other sites]; high 
vs. low volume per CHAARTED criteria5), type of progression at trial entry (per PCWG3: PSA 
only, bone only ± nodal disease, nodal disease only [no bone disease present]: pelvic and 
extrapelvic; visceral [lung, liver, adrenal, CNS] disease [± other sites]), number of prior 
treatments (1, 2, or ≥ 3), class of therapy (eg, prior chemotherapy [yes/no]), alkaline phosphatase 


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(above or below the median at trial Baseline), LDH (above or below the median at trial 
Baseline), and Gleason score (> 7 or ≤ 7 at diagnosis). 
9.6. 
Safety Analyses 
The Safety Analysis Set will be used to evaluate all safety endpoints. 
9.6.1. 
Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 
22.0 or higher and will be graded according to the NCI-CTCAE version 5.0 or higher.  
Summaries of AEs will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that 
emerges or worsens in the period from the first dose of study drug to 30 days after the last dose 
of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last dose of 
zimberelimab (30 days after the last dose of zimberelimab if the patient starts another anticancer 
therapy), whichever is later. 
TEAEs will be summarized by frequency and by MedDRA System Organ Class and Preferred 
Term. Separate tabulations will also be produced for TEAEs assessed as related to study drug(s), 
TEAEs leading to treatment discontinuation, TEAEs leading to death, AESIs, and TEAEs Grade 
≥ 3 in severity. Treatment-emergent SAEs and SAEs related to study drug(s) will also be 
tabulated.  
Incidence of SSEs per PCWG3 criteria, defined as symptomatic failure, radiation or surgery to 
bone, or spinal cord compression, will be reported.1 
9.6.2. 
Clinical Laboratory Assessments 
All statistical analyses of laboratory values will be performed using International System units.  
Shifts in grade (per NCI-CTCAE version 5.0 or higher) from Baseline to the maximum 
post-Baseline grade will be summarized for applicable laboratory data. Laboratory values 
Grade ≥ 3 in severity will be tabulated. 
A listing of individual patient hematology, serum chemistry, and coagulation values outside the 
reference ranges will be provided. This listing will include data from scheduled and unscheduled 
time points. 
9.7. 
Pharmacokinetic Analyses 
Serum samples will be analyzed for SRF617 concentrations using a validated 
ligand-binding-based method. PK parameters based on the actual sample collection times will be 
determined using standard noncompartmental methods using the PK Analysis Set. The PK 
parameters to be assessed include, but are not necessarily limited to:  
Cmax  
Maximum observed serum concentration  
Cmin  
Minimum observed serum concentration prior to administration of subsequent 
dose 


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Evaluations of PK data will include maintenance concentration, accumulation upon 
multiple-dose administration, and immunogenicity analysis, when appropriate. Blood samples 
will be collected for etrumadenant and zimberelimab concentration analysis. Due to the 
limitations of sparse sampling, PK evaluation of etrumadenant and zimberelimab will be limited 
to the maintenance concentrations and descriptive statistics. Additional details on the PK 
analyses will be provided in the SAP.  
9.8. 
Biomarker Analyses  
Biomarker analyses will generally be descriptive in nature. Summary tabulations may be 
produced if data from a sufficient number of patients are collected. Additional details on the 
biomarker analyses will be provided in the SAP.  
Tumor and serum PAP expression levels will be correlated to estimate if serum can provide a 
reliable indication of tumor expression levels. Specifically, a linear regression model will be fit 
to estimate the tumor PAP level versus the serum PAP level. The regression estimate, along with 
a 95% confidence interval, will be provided. Tumor samples will also be assessed for PD-L1 and 
CD39 expression levels and correlation with clinical response parameters, although no formal 
statistical test will be performed. 
Additional biomarkers measured in serum, plasma, blood, and tumor tissues will be analyzed in 
an exploratory fashion. These exploratory analyses may or may not be presented formally. If 
presented, they will be limited to biomarkers for which data from a sufficient number of patients 
are available. 
 


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10. 
TRIAL ADMINISTRATION 
10.1. 
Good Clinical Practice Statement 
This trial is to be performed in accordance with the protocol, the Declaration of Helsinki, the 
International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good 
Clinical Practice (GCP), and all applicable local regulatory requirements. 
10.2. 
Informed Consent 
The Sponsor or its designee will provide a sample patient ICF for modification, as appropriate, 
by the Investigator. The ICF must include all elements required by ICH and GCP and must 
adhere to the IRB/IEC requirements and the ethical principles that have their origin in the 
Declaration of Helsinki. 
The Investigator or his/her staff will explain the nature of the trial, its purpose and associated 
procedures, the expected duration, and the potential risks involved to the patient before 
enrollment. The Investigator or designee will obtain written, informed consent. The patient will 
have ample time and opportunity to ask questions and will be informed about the right to 
withdraw from the trial at any time without any disadvantage and without having to provide a 
reason for this decision. After the discussion regarding the trial, a patient will be asked if they are 
willing to sign and personally date a statement of informed consent. Only if the patient 
voluntarily agrees to sign the informed consent statement and has done so, may he/she enter the 
trial. A copy of the signed and dated ICF will be provided to the patient. The signed ICF is to 
remain in the Investigator’s file, per local requirements. 
The ICF and any other written information provided to the patients will be revised whenever 
important new information becomes available that may be relevant to the patient’s consent, or if 
there is an amendment to the protocol which necessitates a change to the content of the patient’s 
informed consent. The Investigator will inform the patients of changes in a timely manner and 
will ask the patients to confirm continuation of their participation in the trial by their signature on 
the revised ICF (if applicable). Any written ICF and written information must receive the 
approval/favorable opinion of the IRB/IEC in advance of use. Any additional approvals from the 
initial ICF should be forwarded to the Sponsor. 
10.3. 
Patient Confidentiality 
The written ICF will explain that trial data will be stored in a database, maintaining 
confidentiality in accordance with national data legislation. All data processed by the Sponsor or 
its representative(s) will be identified by patient number and trial code. 
The written ICF will also explain that for data verification purposes, authorized representatives 
of the Sponsor, a regulatory authority, and an IRB/IEC may require direct access to parts of the 
hospital or clinic records relevant to the trial that include the patient’s medical history. 
The Investigator must ensure that the patients’ anonymity is maintained. On the eCRFs or other 
documents submitted to the Sponsor, patients should not be identified by their names, but by 
their assigned patient number and trial code. Documents not for submission to the Sponsor, such 
as signed ICF, should be maintained in strict confidence by the Investigator. 


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10.4. 
Institutional Review Board/Ethics Committee Requirements 
The final trial protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB/IEC at each clinical trial site. The Principal Investigator 
must submit written approval to the Sponsor before he or she can enroll any patient into the trial. 
The Principal Investigator is responsible for informing the IRB/IEC of any amendment to the 
protocol. In addition, the IRB/IEC must approve all advertising used to recruit patients for the 
trial. The protocol must be reapproved by the IRB/IEC annually or as applicable. 
Progress reports and notifications of SAEs will be provided to the IRB/IEC according to 
regulations and guidelines. 
10.5. 
Case Report Forms and Source Documentation 
eCRFs will be provided for the recording of all data. The Principal Investigator/subinvestigator 
or designee will record data from all observations, tests, and assessments specified in the 
protocol on the eCRFs provided by the Sponsor. 
10.6. 
Sponsor Monitoring 
Before the first patient is enrolled into the trial, a representative of the Sponsor will visit the trial 
site in person, or remotely as COVID restrictions persist, to: 
• Determine the adequacy of the facilities 
• Discuss with the Investigator(s) (and other personnel involved with the trial) their 
responsibilities about the protocol and the responsibilities of the Sponsor  
During the conduct of the trial, a representative of the Sponsor will have regular contact with the 
clinical trial site and have regular visits to the clinical trial site in person, or remotely as COVID 
restrictions persist, to: 
• Provide information and support the Principal Investigator 
• Confirm that the facilities remain acceptable 
• Confirm that the trial team is adhering to the protocol, data are being accurately 
recorded in the eCRFs, and the investigational product is being properly maintained 
and accountability records are current 
• Perform source data verification with access to all original clinical records for each 
patient 
10.7. 
Data Monitoring Committee 
There will be no formal Independent Data Monitoring Committee.  


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10.8. 
Quality Assurance 
In compliance with GCP and regulatory requirements, the Sponsor, a third party on behalf of the 
Sponsor, regulatory agencies, or IRB/IECs may conduct quality assurance audits at any time 
during or after a trial. The Investigator must agree to allow auditors direct access to all 
trial-related documents including source documents and must agree to allocate his or her time 
and the time of his or her trial staff to the auditors to discuss findings and issues. 
10.9. 
Trial or Clinical Site Termination 
The Sponsor, or designee, reserves the right to terminate the trial or a clinical trial site at any 
time. Conditions that may warrant termination of the trial include, but are not limited to: 
• The discovery of an unexpected, serious, or unacceptable risk to patients enrolled in 
the trial 
• The decision on the part of the Sponsor to suspend or discontinue testing the study 
drug 
• Failure of the Investigator to comply with GCP 
• Submission of knowingly false information from the clinical trial site to the Sponsor 
or regulatory authorities 
• Insufficient adherence to protocol requirements 
If terminating the trial, the Sponsor and the Investigator(s) will ensure that adequate 
consideration is given to the protection of the patients’ interests. 
10.10. 
Duration of the Trial, Expected Duration of Patient Participation, 
and End of Trial 
Patients will continue study treatment for up to 2 years or until documented disease progression 
or unacceptable toxicity. Patients may remain on study drug longer than 2 years with agreement 
from the trial Investigator and Sponsor.  
10.11. 
Records Retention 
All correspondence related to this clinical trial should be kept in appropriate trial files. Records 
of patients, source documents, eCRFs, study drug inventory, and IRB and Sponsor 
correspondence pertaining to this trial must be kept on file. All trial documents must be kept 
secured for a period of 2 years after a marketing application is approved for SRF617, or until 
2 years after shipment and delivery of the study drug for investigational use is discontinued, or as 
long as required by local regulations, whichever is longer. There may be other circumstances for 
which the Sponsor is required to maintain trial records; therefore, the Sponsor should be 
contacted before removing or relocating trial records for any reason. 
10.12. 
Publications 
Publication by the clinical trial site(s) of any data from this trial must be carried out in 
accordance with the Clinical Trial Agreement. 


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11. 
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progression on a first-line ARTA in a US community oncology setting. Urol Oncol. 
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the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel 
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32. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, et al. Ipilimumab 
versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer 
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double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700-12. 
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Adenosine A2B Receptor Constitutive Activity as a Promoter of Prostate Cancer Cell 
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37. Zimmermann H. Prostatic acid phosphatase, a neglected ectonucleotidase. Purinergic Signal. 
2009;5(3):273-5. 
38. Antonioli L, Blandizzi C, Pacher P, Hasko G. Immunity, inflammation and cancer: a leading 
role for adenosine. Nat Rev Cancer. 2013;13(12):842-57. 
39. Di Virgilio F, Sarti AC, Falzoni S, De Marchi E, Adinolfi E. Extracellular ATP and P2 
purinergic signalling in the tumour microenvironment. Nat Rev Cancer. 2018;18(10):601-18. 
40. Spychala J. Tumor-promoting functions of adenosine. Pharmacol Ther. 2000;87(2-3):161-73. 
41. Blay J, White TD, Hoskin DW. The extracellular fluid of solid carcinomas contains 
immunosuppressive concentrations of adenosine. Cancer Res. 1997;57(13):2602-5. 
42. Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, et al. A2A adenosine 
receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A. 2006;103(35):13132-
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43. Hasko G, Linden J, Cronstein B, Pacher P. Adenosine receptors: therapeutic aspects for 
inflammatory and immune diseases. Nat Rev Drug Discov. 2008;7(9):759-70. 
44. Allard B, Longhi MS, Robson SC, Stagg J. The ectonucleotidases CD39 and CD73: Novel 
checkpoint inhibitor targets. Immunol Rev. 2017;276(1):121-44. 
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47. Sun X, Wu Y, Gao W, Enjyoji K, Csizmadia E, Muller CE, et al. CD39/ENTPD1 expression 
by CD4+Foxp3+ regulatory T cells promotes hepatic metastatic tumor growth in mice. 
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48. Kunzli BM, Bernlochner MI, Rath S, Kaser S, Csizmadia E, Enjyoji K, et al. Impact of CD39 
and purinergic signalling on the growth and metastasis of colorectal cancer. Purinergic Signal. 
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49. Perrot I, Michaud HA, Giraudon-Paoli M, Augier S, Docquier A, Gros L, et al. Blocking 
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and CD39 in the immunological control of tumor metastases. Oncoimmunology. 
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51. Feng L, Sun X, Csizmadia E, Han L, Bian S, Murakami T, et al. Vascular CD39/ENTPD1 
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55. Xu H, Wang F, Li H, Ji J, Cao Z, Lyu J, et al. Prostatic Acid Phosphatase (PAP) Predicts 
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56. Kong HY, Byun J. Emerging roles of human prostatic Acid phosphatase. Biomol Ther 
(Seoul). 2013;21(1):10-20. 
57. Subudhi SK, Wise DR, Liu ST, et al. ARC-6: A Phase 1b/2, open-label, randomized platform 
study evaluating the efficacy and safety of etrumadenant (AB928)-based treatment combinations 
in patients with metastatic castrate-resistant prostate cancer. Poster presented at: ESMO Virtual 
Congress 2020; September 19-21, 2020. 
58. Yadav V, Chi L, Zhao R, Tourdot BE, Yalavarthi S, Jacobs BN, et al. Ectonucleotidase 
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60. Willingham SB, Ho PY, Hotson A, Hill C, Piccione EC, Hsieh J, et al. A2AR Antagonism 
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61. Holland PM. Targeting the adenosine axis to treat cancer. Presented at the Brisbane 
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62. Powderly J, Spira A, Gutierrez R, DiRenzo D, Udyavar A, Karakunnel JJ, et al. Phase 1 
evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy 
or AB122 (anti-PD-1) in patients (pts) with advanced malignancies. Ann Oncol. 
2019;30(suppl_5):v475-v532. 
63. Sachdev J, Prawira A, Chaudhry A, et al Efficacy and safety of AB928 plus pegylated 
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64. Cecchini M, Modiano M, Braiteh F, Gardner OS, Gilbert HN, DiRenzo D, et al. Abstract LB-
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66. Bendell J, Bauer T, Patel M, Falchook G, Karlix JL, Lim E, et al. Abstract CT026: Evidence 
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68. Lim EA, Bauer TM, Patel MR, Falchook GS, Karlix JL, Choe JH, et al. A phase I, open-
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73. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New 
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APPENDIX 1. LIST OF PROHIBITED OR CAUTIONARY 
MEDICATIONS FOR CONCOMITANT USE WITH 
ETRUMADENANT 
Due to the potential risk for drug-drug interactions, the following medications are either 
prohibited or require dose modification for concomitant use with etrumadenant (Table 11). This 
list is intended for use as a guidance document for site staff and may not be exhaustive. 
Specific details regarding the potential for etrumadenant or its active metabolites to inhibit or 
induce CYP-mediated metabolism as well as interact with drug transporters are provided in the 
etrumadenant Investigator Brochure. 
For questions regarding the potential drug-drug interaction risk for medications not included 
herein, please follow up with the trial Medical Monitor. 
Table 11: 
List of Prohibited or Cautionary Medications for Concomitant Use With 
Etrumadenant 
Medication name 
Concomitant use with 
etrumadenant 
Dose modification guidance 
Loperamide 
Administer with caution 
• 
Coadministration with etrumadenant may 
result in reduced or increased exposure to 
loperamide and may be associated with 
potential loss of efficacy or greater risk of 
side effects. 
• 
If initiating new antidiarrheal therapy, avoid 
loperamide and administer alternate 
treatment if possible (cholestyramine, 
alosetron, bismuth subsalicylate). 
• 
If loperamide is an ongoing concomitant 
therapy at the time etrumadenant is initiated, 
loperamide may be continued with more 
frequent monitoring for safety and/or loss of 
efficacy in accordance with institutional 
standards. 
Colchicine 
Prohibited for patients with 
renal or hepatic impairment 
• 
Administer alternate treatment for associated 
symptoms. 


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Medication name 
Concomitant use with 
etrumadenant 
Dose modification guidance 
Administer with caution in 
patients without renal or 
hepatic impairment 
• 
Coadministration with etrumadenant may 
result in reduced or increased exposure to 
colchicine and may be associated with 
potential loss of efficacy or greater risk of 
side effects. 
• 
Continue colchicine with more frequent 
monitoring for safety and/or loss of efficacy 
in accordance with institutional standards. 
Reduce colchicine dose by 50% in response 
to treatment-emergent side effects. 
Apixaban 
Administer with caution 
• 
Continue etrumadenant at the planned dose 
and implement additional safety monitoring 
in accordance with institutional standards. 
• 
Reduce apixaban dose by 50% in response 
to treatment-emergent side effects. 
Rivaroxaban 
Administer with caution 
• 
If initiating new anticoagulant therapy, 
avoid rivaroxaban and administer alternate 
treatment for associated symptoms. 
• 
If rivaroxaban is an ongoing concomitant 
therapy at the time etrumadenant is initiated, 
rivaroxaban may be continued with more 
frequent monitoring for safety and/or loss of 
efficacy in accordance with institutional 
standards. 
Dabigatran 
Prohibited for patients with 
severe renal impairment 
• 
Administer alternate treatment for associated 
symptoms. 
Administer with caution in 
patients with moderate renal 
impairment 
• 
Coadministration with etrumadenant may 
result in increased exposure to dabigatran. 
• 
Reduce dabigatran dose to 75 mg and 
implement additional safety monitoring in 
accordance with institutional standards. 
Rosuvastatin 
(> 10 mg QD) 
Administer with caution 
• 
Coadministration with etrumadenant may 
result in increased exposure to rosuvastatin. 
• 
Implement additional safety monitoring in 
accordance with institutional standards. 
Rosuvastatin 
(≤ 10 mg QD) 
Permitted 
N/A 


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Medication name 
Concomitant use with 
etrumadenant 
Dose modification guidance 
Atorvastatin 
Permitted 
• 
Coadministration with etrumadenant may 
result in decreased exposure to atorvastatin. 
• 
Continue current dose regimen and monitor 
for loss of efficacy. 
Simvastatin 
Permitted 
• 
Coadministration with etrumadenant may 
result in decreased exposure to simvastatin. 
• 
Continue current dose regimen and monitor 
for loss of efficacy. 
Fluvastatin 
(> 20 mg BID) 
Administer with caution 
• 
Coadministration with etrumadenant may 
result in increased exposure to fluvastatin. 
• 
Implement additional safety monitoring in 
accordance with institutional standards. 
Fluvastatin 
(≤ 20 mg BID) 
Permitted 
N/A 
Opioid agonists 
and antagonists 
Naloxegol: Administer with 
caution 
• 
Coadministration with etrumadenant may 
result in reduced naloxegol exposure and 
efficacy. 
• 
If initiating new opioid therapy, avoid 
naloxegol and administer alternate treatment 
for associated symptoms. 
• 
If naloxegol is an ongoing concomitant 
therapy at the time etrumadenant is initiated, 
naloxegol may be continued with more 
frequent monitoring for loss of efficacy. 
Methylnaltrexone: Permitted 
N/A 
Oxymorphone, 
Hydromorphone, 
Oxycodone, Hydrocodone, 
Codeine, Morphine: 
Administer with caution 
• 
Coadministration with etrumadenant may 
result in reduced or increased opioid 
exposure. 
• 
Implement additional monitoring for 
supratherapeutic opioid dose-related adverse 
events as well as subtherapeutic opioid dose-
related loss of efficacy. 
Fentanyl: Administer with 
caution 
• 
Coadministration with etrumadenant may 
result in reduced fentanyl exposure. 
• 
Implement additional monitoring for 
subtherapeutic opioid dose-related loss of 
efficacy. 


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Medication name 
Concomitant use with 
etrumadenant 
Dose modification guidance 
Methadone: Prohibited 
• 
Administer alternate treatment for associated 
symptoms. 
Cannabinoids 
Tetrahydrocannabinol, 
Cannabidiol (oral, 
intravenous, inhaled 
formulations): Administer 
with caution 
• 
Coadministration with etrumadenant may 
result in reduced cannabinoid exposure. 
• 
Implement additional monitoring for loss of 
efficacy. 
Degarelix 
Administer with caution 
• 
Coadministration with etrumadenant may 
result in reduced or increased exposure to 
degarelix and may be associated with 
potential loss of efficacy or greater risk of 
side effects. 
• 
It is recommended to avoid degarelix. If 
coadministration is unavoidable, stagger 
etrumadenant and degarelix doses by 
≥ 6 hours. Implement additional monitoring 
for safety and/or loss of efficacy in 
accordance with institutional standards. If 
loss of efficacy is observed, increase 
degarelix dose to 240 mg. 
Digoxin 
Prohibited 
• 
Administer alternate treatment for associated 
symptoms. 
Abbreviations: BID = twice daily; N/A = not applicable; QD = once daily. 
Note: The half-life of etrumadenant is approximately 20 hours. A washout period of at least 4 days (equivalent to 
approximately 5 half-lives) following the last dose etrumadenant is therefore recommended prior to initiation of any 
medication listed in in this table. 
 


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APPENDIX 2. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS 
Grade 
ECOG 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, eg, light housework, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities; 
up and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled. Cannot carry on any self-care; totally confined to bed or 
chair 
5 
Dead 
Source: Oken et al, 1982. 72 
 
 
 


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APPENDIX 3. RESPONSE CRITERIA 
Table 12: 
PCWG3 Baseline Assessment of Disease – Amended for Trial SRF617-201 
Parameter 
Assessments 
Histology 
• 
Adenocarcinoma 
• 
Excluded from Trial SRF617-201: 
o Adenocarcinoma with small-cell or neuroendocrine features 
o Small-cell carcinoma 
• 
Report Gleason score sum for primary tumor at diagnosis, when available 
• 
Consider re-biopsy of metastatic disease 
Clinical 
• 
Age, pain, analgesic use, performance status, comorbidities, history, physical examination; 
prior local therapy; TNM stage and Gleason score at diagnosis; and PSA 
Prior systemic treatment 
• 
Record each line of systemic therapy (single agent or combination) in order of 
administration, including start and stop dates, dose(s), and schedule(s), the disease state in 
which it was administered, and response (resistant versus sensitive) on the basis of PSA or 
radiologic findings, if appropriate 
Prior radiation therapy 
• 
Site, administered dose per fraction, treatment duration if applicable and when available 
Blood-based biomarkers 
• 
Host: CBC with differential, ALP, kidney/liver function, albumin, LDH, testosterone 
• 
Tumor: PSA and PSA kinetics (PSADT)a 
Imaging 
Prostate/Prostate bed 
• 
Endorectal MRI (cross-sectional imaging of prostate region, if applicable) 
Nodal 
CT or MRI: 
• 
Nodes ≥ 1.5 cm in short axis are considered measurable; nodes ≥ 1.0 and < 1.5 cm in short 
axis are considered pathologic according to clinical discretion, and nontarget; nodes < 1.0 cm 
in short axis are considered nonpathologic 


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Parameter 
Assessments 
• 
Record pelvic and extra-pelvic nodal disease separately, up to 5 nodes in total; pelvic nodes 
should be classified as locoregional and extrapelvic (retroperitoneal, mediastinal, thoracic, or 
other) nodes as metastatic 
• 
Record new lesions vs growth of pre-existing lesions, and sites of new lesions 
Visceral 
CT or MRI: 
• 
Record individual sites of spread separately; up to 5 lesions per site 
• 
Lesions ≥ 1.0 cm in longest dimension are considered measurable 
• 
Record new lesions vs growth of pre-existing lesions, and sites of new lesions 
Bone 
99mTc MDP  
• 
Record new lesions and sites of new lesions 
Tumor profiling for determinants of 
prognostic, predictive, and resistance 
biomarkers 
• 
Consider re-biopsy of metastatic or locally recurrent lesion(s) for biologic characterization 
• 
Catalog prior biopsy (or cfDNA/ctDNA) genomic results 
Abbreviations: 99mTc MDP = 99mTc methylene diphosphate; ALP = alkaline phosphatase; CBC = complete blood count; CEA = carcinoembryonic antigen; 
cfDNA= cell free DNA; CT = computed tomography; ctDNA = circulating tumor DNA; HRQoL = health-related quality of life; LDH = lactate dehydrogenase; 
MRI = magnetic resonance imaging; PCWG3 = Prostate Cancer Working Group 3; PSA = prostate-specific antigen; PSADT = prostate-specific antigen doubling 
time; TNM = tumor, node, metastasis. 
a PSADT should be calculated using a linear regression model of the normal logarithm of PSA and time. The calculation should be based on (1) at least 3 
consecutive PSA values with each value ≥ 0.2 ng/dL, (2) inclusion of the most recent PSA values during androgen deprivation therapy, and (3) interval 
between first and last PSA values of ≥ 8 weeks but ≤ 12 months. 
Source: Scher, 2016.1 
 
 


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Table 13: 
PWCG3 Criteria for Progression at Trial Entry 
Variable 
Criteria 
Blood-based 
PSA 
• 
Obtain sequence of rising values at a minimum of 1-week intervals 
• 
1 ng/mL is the minimal starting value if confirmed rise is only indication of progression  
• 
If nonmeasurable disease, estimate pretherapy PSADT if ≥ 3 values available ≥ 4 weeks apart 
Imaging 
Nodes 
• 
Nodal progression sufficient for trial entry independent of PSA  
• 
Measurable lesions not required for entry 
• 
Modified RECIST v1.1 criteria, separate pelvic and extra-pelvic disease, up to 5 nodal lesions total recorded  
• 
Previously normal (< 1.0 cm) lymph nodes must have grown by ≥ 5 mm in the short axis from Baseline or 
nadir and be ≥ 1.0 cm in the short axis to be considered to have progressed 
• 
If the node progresses to ≥ 1.5 cm in the short axis, it is measurable; nodes that have progressed to 1.0 to 
< 1.5 cm are pathologic, subject to clinical discretion, and nonmeasurable 
• 
For existing pathologic adenopathy, progression is defined per RECIST v1.1 
• 
Record presence of nodal and/or visceral disease separately 
o Nodal sites: 
 
Locoregional: pelvic only 
 
Extra-pelvic: retroperitoneal, mediastinal, thoracic, or other 
Viscera 
• 
Visceral progression sufficient for trial entry independent of PSA (recorded separately by site of spread [lung, 
liver, adrenal, CNS]); up to 5 lesions per site of metastatic disease 
• 
Measurable lesions not required for entry 
• 
Use RECIST criteria to record visceral lesions as target or nontarget 
• 
Record presence of nodal and/or visceral disease separately (visceral sites: lung, liver, adrenal, CNS) 
Prostate/Prostate bed 
(primary site) 
• 
Record prior treatment of primary tumor (eg, surgery, radiation, cryoablation, radiofrequency ablation, none, 
other) 
• 
Perform directed pelvic imaging (CT, MRI, PET/CT, endorectal MRI, transrectal ultrasound) to document 
presence or absence of disease 


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Variable 
Criteria 
Bone 
• 
2 new lesions 
• 
Confirm ambiguous results by other imaging modalities (eg, CT or MRI), but only positivity on bone scan 
defines metastatic disease to bone 
Other sites of disease 
• 
Patients with treated epidural lesions and no other epidural progression are eligible 
Type of progression at trial entry 
 
• 
Report separately: 
o PSA only 
o Bone only ± nodal disease 
o Nodal disease only (no bone disease present): pelvic and extrapelvic 
o Visceral (lung, liver, adrenal, CNS) disease (± other sites) 
• 
Record new lesions and site of new lesions versus growth of pre-existing lesions, or both 
Abbreviations: CNS = central nervous system; CT = computed tomography; MRI = magnetic resonance imaging; PET =positron emission tomography; 
PSA = prostate-specific antigen; PSADT = prostate-specific antigen doubling time; RECIST = Response Evaluation Criteria in Solid Tumors 
Source: Scher, 2016.1 
 
 


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SRF617 
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Table 14: 
RECIST Version 1.1 Lesion Response 
Evaluation of target lesions 
Complete response (CR): 
Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to 
< 10 mm in short axis 
Partial response (PR): 
At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum 
of diameters 
Progressive disease (PD): 
At least a 20% increase in the sum of diameters of target lesions from the smallest value on trial 
(including Baseline, if that is the smallest). The sum of diameters must also demonstrate an absolute 
increase of at least 5 mm. Or, the appearance of one or more lesions 
Stable disease (SD): 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD 
Evaluation of nontarget lesions 
Complete response (CR): 
Disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size 
(< 10 mm in short axis), and normalization of tumor marker level 
Non-CR/non-PD:  
Persistence of 1 or more nontarget lesion(s) or/and maintenance of tumor marker level above the 
normal limits 
Progressive disease (PD): 
Unequivocal progression of existing nontarget lesions. Or, the appearance of one or more lesions  
Note: Evaluations for target, nontarget, and new lesions are to be considered together to assess an overall response status at a time point as detailed in Table 15. 
For the overall response of CR or PR, confirmation of the response status at a subsequent time point at least 4 weeks apart from the initial observation is 
recommended.  
Source: Eisenhauer et al, 2009.73 
 
 


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Table 15: 
Evaluation of Overall Response by RECIST Version 1.1 
Target lesions 
Nontarget lesions 
New lesions 
Overall response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or no 
PD 
Any 
PD 
Yes or no 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR = complete response; NE = inevaluable; PD = progressive disease; PR = partial response/ remission, SD = stable disease. 
Source: Eisenhauer et al, 2009.73 
 

SAP_001.pdf: 
Protocol No.: SRF617-201 
A Phase 2 Trial of SRF617 in Combination with 
AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients 
with Metastatic Castration-Resistant Prostate Cancer 
Statistical Analysis Plan 
Version: v2.0 
Date: 19 June 2023 
NCT #: NCT05177770


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
Protocol Version: 1.1 
Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
2 
 
SIGNATURE PAGE 
 
 
Surface Oncology, Inc. 
Date 
 
Surface Oncology, Inc. 
Date 
 
 
Caidya 
 
Date 
 
 
19-Jun-2023
19-Jun-2023
19-Jun-2023


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
Protocol Version: 1.1 
Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
3 
 
Table of Contents 
Modification history................................................................................................................... 5 
Abbreviations ............................................................................................................................. 6 
1 
Introduction ........................................................................................................................ 8 
1.1 
Discrepancies Between the SAP and the Protocol ......................................................... 8 
2 
Study Design....................................................................................................................... 8 
2.1 
Study Objectives and Endpoints .................................................................................... 9 
2.2 
Study Treatment ............................................................................................................. 9 
2.3 
Sample Size Considerations ......................................................................................... 10 
3 
Analysis Sets..................................................................................................................... 10 
3.1 
Enrolled Analysis Set ................................................................................................... 10 
3.2 
Safety Lead-in Evaluable Analysis Set ........................................................................ 10 
3.3 
Safety Analysis Set ...................................................................................................... 10 
3.4 
Response-Evaluable Analysis Set ................................................................................ 11 
4 
General Considerations ..................................................................................................... 11 
4.1 
Programming Environment .......................................................................................... 11 
4.2 
General Statistical Methods ......................................................................................... 11 
4.3 
Subgroups .................................................................................................................... 12 
4.4 
Multiple Comparison/Multiplicity ............................................................................... 12 
5 
Definitions & data Handling conventions ........................................................................ 12 
5.1 
Study Day, Duration, and Study Periods ..................................................................... 12 
5.2 
Analysis Visit Windows .............................................................................................. 12 
5.3 
Data Derivation ............................................................................................................ 13 
5.4 
Missing Data ................................................................................................................ 13 
5.4.1 
Partial or Missing Dates and Time ....................................................................... 13 
5.4.2 
Other Missing Values ........................................................................................... 13 
6 
Study Population, Conduct and Patient Disposition ......................................................... 13 
6.1 
Analysis Sets ................................................................................................................ 13 
6.2 
Patient Disposition ....................................................................................................... 14 
6.3 
Protocol Deviations ...................................................................................................... 15 
7 
Demographics and Basleine Characteristics ..................................................................... 16 
7.1 
Demographics .............................................................................................................. 16 
7.2 
Cancer History ............................................................................................................. 16 


 
Sponsor: Surface Oncology 
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4 
 
7.3 
Prior Systemic Cancer Therapies ................................................................................. 17 
7.4 
Prior Radiation Therapies ............................................................................................ 18 
7.5 
Medical History ........................................................................................................... 19 
8 
Protocol-Required Drug Exposure and Compliance ........................................................ 19 
8.1 
Study Drug Exposure ................................................................................................... 19 
9 
Prior and Concomitant Therapies ..................................................................................... 20 
9.1 
Prior and Concomitant Medications ............................................................................ 20 
9.2 
Prior and Concomitant Procedures .............................................................................. 20 
10 Efficacy Analysis .............................................................................................................. 20 
10.1 
Definitions of Efficacy-related Variables .................................................................... 21 
10.1.1 
Best Overall Response .......................................................................................... 21 
10.1.2 
PSA50 Response .................................................................................................... 21 
10.1.3 
Primary Composite Response Rate ...................................................................... 21 
10.1.4 
Efficacy Endpoints Excluded from Analysis ....................................................... 21 
10.2 
Analysis of Efficacy Variables .................................................................................... 22 
10.2.1 
Primary Composite Response Rate ...................................................................... 22 
11 Safety Analyses ................................................................................................................ 22 
11.1 
Adverse Events ............................................................................................................ 22 
11.2 
Deaths .......................................................................................................................... 23 
11.3 
Vital Signs and Body Measurements ........................................................................... 23 
11.4 
Clinical Laboratory ...................................................................................................... 23 
11.4.1 
Hematology, coagulation, clinical chemistry, thyroid function tests, testosterone, 
PAP and PSA ........................................................................................................................... 23 
11.4.2 
Urinalysis .............................................................................................................. 24 
11.4.3 
Serology ................................................................................................................ 24 
11.5 
ECG.............................................................................................................................. 24 
11.6 
Eastern Cooperative Oncology Group (ECOG) Performance Status .......................... 24 
12 Other Analyses ................................................................................................................. 25 
12.1 
Pharmacokinetic and Pharmacokinetic/Pharmacodynamic analyses ........................... 25 
12.2 
Pharmacodynamic Analyses ........................................................................................ 25 
12.3 
Immunogenicity Analyses ........................................................................................... 25 
13 Interim Analyses ............................................................................................................... 25 
14 Statistical Analyses for Safety Monitoring ....................................................................... 25 
15 References ........................................................................................................................ 25 
 
 


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
Protocol Version: 1.1 
Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
5 
 
 
MODIFICATION HISTORY 
 
Version 
Version Date  
Author 
Changes from Previous Version 
Final 1.0 
29SEP2022 
 NA 
Final 2.0 
19JUN2023 
 Combined related TEAE to TEAE related 
to any drug; 
Kept summary of “Primary Composite 
Response Rate”, but removed other 
efficacy analyses;  
Removed the analysis sets that are not used 
in final analysis.  
 
 
 


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
Protocol Version: 1.1 
Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
6 
 
ABBREVIATIONS 
ADA 
Antidrug antibody 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
BP 
Blood Pressure 
bpm 
Beats per minute 
CFB 
Change from Baseline 
CR 
Complete Response 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTMS 
Clinical Trial Management System 
DCR 
Disease control rate 
DoR 
Duration of Response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EoT 
End of Treatment 
iv 
Intravenously 
MedDRA 
Medical Dictionary for Regulatory Activities 
mCRPC 
Metastatic Castration-Resistant Prostate Cancer 
mg 
milligram 
mL 
milliliter 
mmHg 
millimeter of mercury 
NCI 
National Cancer Institute  
NE 
Not Evaluable 
ng 
nanogram 
ORR 
Objective Response Rate 
PAP 
Prostatic Acid Phosphatase 
PCWG 
Prostate Cancer Working Group 
PD 
Progressive Disease 
PD-L1 
Programmed Death-Ligand 1 
PDMP 
Protocol Deviations Management Plan 
PFS 
Progression Free Survival 
PK 
Pharmacokinetics 
PN 
Preferred Name 
p.o. 
per os, by mouth 
PR 
Partial Response 
PSA 
Prostate-Specific Antigen 
PSA30 
At least 30% decline in PSA 
PSA50 
At least 50% decline in PSA 
PT 
Preferred Term 
q2w 
Once every 2 weeks 
q4w 
Once every 4 weeks 
q.d. 
quaque die, once a day 
QTc 
Heart rate-corrected QT interval 
QTcF 
QT Interval corrected with Fridericia’s method 
RECIST 
Response Evaluation Criteria in Solid Tumors 


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
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Version: final v2.0 
           Version date: 19JUN2023 
 
7 
 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
SRC 
Safety Review Committee 
SSE 
Symptomatic Skeletal Event 
TEAE 
Treatment Emergent Adverse Event 
TLF 
Tables, Listings, and Figures 
 
 


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
Protocol Version: 1.1 
Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
8 
 
1 
INTRODUCTION 
The objective of this document is to detail the statistical methodology to be used in the 
statistical analyses of clinical protocol SRF617-201 “A Phase 2 Trial of SRF617 in 
Combination With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With 
Metastatic Castration-Resistant Prostate Cancer” Amendment 1.1 dated on 30JUL2021) and 
Patient Case Report Forms (CRFs version 3.0 dated on 19MAY2022)  
Pharmacokinetics and pharmacodynamics analyses, with the exception of data summaries, and 
reporting are not included in this analysis plan. 
1.1 
Discrepancies Between the SAP and the Protocol 
Surface (sponsor) terminated the study when 15 subjects received treatment. The abbreviated 
analysis will focus on safety assessments. 
Pharmacokinetics Analysis Set, Blood Biomarker Analysis Set, Tumor Biopsy Analysis Set, 
and Immunogenicity Analysis Set, and corresponding analyses are removed from this SAP. 
2 
STUDY DESIGN 
This is a Phase 2, open-label, safety and preliminary efficacy trial in patients with mCRPC who 
have progressed on or after prior ARSI therapy. The study will employ a 2-stage design with 
an integrated safety lead-in for the triplet combination of SRF617, etrumadenant, and 
zimberelimab.  
Stage 1 will enroll approximately 17 patients, including the Safety Lead-in that will initially 
treat 6 patients. After the first 6 patients have been enrolled, enrollment will be paused until 
these patients have received 1 cycle of the triplet combination and the Safety Review 
Committee has reviewed the aggregate safety data. Once the SRC deems it safe to proceed, an 
additional 11 patients will be enrolled.  
Based on an evaluation of safety and response data, the trial will proceed to the Stage 2 
expansion if ≥ 1 radiographic complete response (CR)/partial response (PR) or prostate-
specific antigen (PSA) responses (defined as a ≥ 50% decline [PSA50]) according to the Prostate 
Cancer Working Group 3 (PCWG3) criteria are observed in 17 evaluable patients. An 
additional 23 patients will be enrolled in Stage 2 for further evaluation of the safety and efficacy 
of the combination. At the end of Stage 2, at least 8 responses (radiographic responses or PSA 
response) are needed to claim preliminary efficacy of the study treatment.  
Tumor biopsies are optional; they will be performed to explore potential biomarkers of 
response to the combination in patients who consent to the procedure, who have non-bone 
metastases amenable to biopsy, and for whom the procedure is deemed safe.  
Patients will continue to receive study drug for up to 2 years or until documented disease 
progression or unacceptable toxicity. Patients may remain on study drug longer than 2 years 
with agreement from the trial Investigator and Sponsor. 
In November 2022, the Sponsor announced that development of SRF617 would be 
discontinued. Patients enrolled and/or consented for treatment on SRF617-201 were permitted 
to continue treatment per study protocol, but additional patients were not enrolled.   Importantly 
the decision to discontinue development of SRF617 was a business decision; there were no 
safety concerns.  As of 19JUN2023, 15 subjects received treatment. 


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
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Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
9 
 
2.1 
Study Objectives and Endpoints 
Primary Objectives 
Primary Endpoints 
• 
To evaluate the preliminary efficacy of 
SRF617 administered in combination with 
etrumadenant and zimberelimab as 
determined by objective response and PSA 
decline 
• 
To evaluate the safety and tolerability of the 
combination 
• 
The proportion of patients with a response, 
defined as PSA50 response (≥50% decline) 
and/or radiographic objective response of 
CR or PR per PCWG3 criteria 
• 
Incidence and severity of AEs 
Secondary Objectives 
Secondary Endpoints 
• 
To evaluate additional preliminary efficacy 
parameters of the combination including 
objective response rate (ORR), PSA 
response, clinical benefit, duration of 
response, and radiologic progression-free 
survival (PFS) 
• 
To evaluate the PK of SRF617 when 
administered in combination with 
etrumadenant and zimberelimab 
• 
To characterize additional safety parameters 
including development of antidrug 
antibodies (ADAs) and symptomatic 
skeletal events (SSEs) 
• 
ORR per PCWG3 criteria, ORR per 
Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1, duration of 
response, disease control rate, PSA50 
response, PSA decline ≥ 30% (PSA30) 
response, time to PSA progression, 
radiographic PFS, and landmark PFS rate at 
6 and 12 months 
• 
Serum concentrations of SRF617 
• 
Percentage of patients with ADAs to 
SRF617 
• 
Incidence of SSEs 
Exploratory Objectives 
Exploratory Endpoints 
• 
Explore potential biomarkers of response 
and/or safety of the combination 
• 
Explore the effects of the triplet on 
peripheral blood immune cell subsets and 
circulating serum cytokines and chemokines 
• 
Explore the biological effects of the triplet 
on tumor cells and immune cell populations 
in the tumor microenvironment 
• 
Explore germline DNA polymorphic 
variations in relation to the PK, 
pharmacodynamics, safety, and/or 
preliminary efficacy 
• 
Explore correlations between prostate 
cancer biomarkers in tumors with 
biomarkers in serum in patients who 
undergo tumor biopsy 
• 
Explore correlations between prostate 
cancer biomarkers in tumors with clinical 
response parameters in patients who 
undergo tumor biopsy 
• 
Changes in selected blood and tumor tissue 
biomarkers 
• 
Germline DNA polymorphic sequence 
variations in relation to the PK, 
pharmacodynamics, safety, and/or 
preliminary efficacy of SRF617 
• 
Serum prostatic acid phosphatase (PAP) 
levels 
• 
PAP expression levels in tumors in patients 
who undergo tumor biopsy 
• 
Programmed death-ligand 1 (PD-L1) and 
CD39 expression levels in tumors in 
patients who undergo tumor biopsy 
 
2.2 
Study Treatment  
Treatment cycles are 28 days in duration.  


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
Protocol Version: 1.1 
Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
10 
 
Study Drug 
Dosing Route and Schedule 
Initial 
Dose  
1st 
Reduction 
2nd 
Reduction 
SRF617 
iv q2w on Days 1 and 15 of each cycle 1400 mg  
700 mg 
350 mg 
Etrumadenant 
orally at a daily dose 
150 mg  
100 mg 
75 mg 
Zimberelimab 
iv q4w on Day 1 of each cycle 
480 mg  
NA 
NA 
2.3 
Sample Size Considerations 
This trial will enroll approximately 40 patients. A patient is enrolled in the trial after they have 
provided informed consent and met all trial eligibility criteria.  
A 2-stage design will be implemented. Stage 1 will include a 6-patient Safety Lead-in followed by 
enrollment of an additional 11 patients for a total of 17 patients. At least 1 radiographic CR/PR or 
2 PSA50 responses by PCWG3 criteria out of 17 evaluable patients must be observed in order to 
consider opening Stage 2, which will enroll an additional 23 patients for further evaluation of the 
safety and efficacy of the triplet. The trial will have met its primary endpoint if at least 8 patients 
in total achieve a response.  
The sample size for this triplet combination therapy dose expansion is based on a null hypothesis 
of a 10% composite response rate (PSA50 or CR/PR) with PD-1 blockade alone versus the alternate 
hypothesis that the composite response rate is 30%, with a calculated alpha of 0.040 and power of 
0.93.  
 
3 
ANALYSIS SETS 
3.1 
Enrolled Analysis Set  
The enrolled analysis set includes all patients who provided informed consent and met all study 
eligibility criteria as recorded in the eCRF. Patients who are later found to be incorrectly 
enrolled are also included this analysis set, but they may be excluded from some or all other 
analysis sets according to an agreement to be reached and documented in the Final Data Review 
Decisions document before database lock. 
3.2 
Safety Lead-in Evaluable Analysis Set  
The Safety Lead-in Evaluable Analysis Set is defined as the first 6 patients enrolled in Stage 1 
who completed at least 50% of the prescribed combination therapy doses during the first cycle 
of therapy (D1–28) or who received less than 50% of the prescribed combination therapy doses 
due to any Grade ≥ 3 related AE (including relationship to SRF617, Etrumadenant and/or 
Zimberelimab as Definite, Probable, and/or Possible ) during the first cycle of therapy (D1–28).  
This analysis set will be used to assess the preliminary safety of the combination therapy in the 
Safety Lead-in Period.  
3.3 
Safety Analysis Set  
The Safety Analysis Set is defined as all patients who received any amount of SRF617. This 
analysis set will be the primary analysis set for all safety endpoints, excluding safety lead-in 
evaluation. 


 
Sponsor: Surface Oncology 
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11 
 
3.4 
Response-Evaluable Analysis Set  
The Response-Evaluable Analysis Set is defined as all enrolled patients who received SRF617 
and had at least 1 post-Baseline response assessment (including PSA assessment and/or tumor 
assessment) or who discontinued the treatment phase because of radiographic or symptomatic 
disease progression (including death caused by disease progression) within 6 weeks (+ 2-week 
window) of the first dose of SRF617. This analysis set will be the primary analysis set for the 
primary efficacy endpoint and other efficacy endpoints. 
 
4 
GENERAL CONSIDERATIONS 
4.1 
Programming Environment 
Unless otherwise specified, all analyses will be conducted using SAS version 9.4 or later.  
4.2 
General Statistical Methods 
The statistical analyses will be presented for the different analysis sets being defined in Section 
3.  
Descriptive Summaries: 
In general, numerical variables will be summarized using descriptive statistics, displaying the 
number of patients in the analysis set, the number of patients with data, sample mean, sample 
standard deviation (calculated as the square root of an unbiased variance estimate), sample 
median, minimum (min) and maximum (max).  
Categorical variables will be summarized by using frequency counts and percentages. In 
addition, the number of patients with missing values will be displayed. Unless otherwise 
specified, the denominators used for calculating sample proportions will be the number of 
patients in the specified statistical analysis set (or a subset of the statistical analysis set under 
use). 
Presentation Conventions: 
Means and medians will be presented by 1 additional decimal place and standard deviation will 
be presented by 2 additional decimal places than the original data. Minimum and maximum 
values will be presented using the same number of decimal places as the original data. If not 
otherwise stated, percentages will be presented to 1 decimal place. However, when the 
percentage (or estimated proportion) is 100% exactly, no decimal place will be shown, whereas 
a presented 100.0% implies that the percentage is in the half-open interval [99.95%, 100%). 
The number of decimal places may be adjusted, e.g., if the above default choices may lead to 
misinterpretation of the presented data. 
In general, rounding will only occur when presenting data but not when analyzing data. By 
default, presented data will be rounded to the nearest required presentation precision, with a 
half-up tie-breaking rule. However, when presenting confidence intervals, the lower interval 
limit will always be rounded down and the upper interval limit will always be rounded up in 
order preserve the claimed (exact or asymptotic) confidence level. When either limit is outside 
of the parameter space (e.g., below 0 or above 1 for proportions), the interval will be truncated 
at the boundary of the parameter space.  


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
Protocol Version: 1.1 
Statistical Analysis Plan 
Version: final v2.0 
           Version date: 19JUN2023 
 
12 
 
If the number of patients in a category is 0, then percentage will not be displayed, and only a 
count of 0 will be shown. However, structural zeros (e.g., when the count is deemed to be 0 
before obtaining actual data), missing data or inapplicable/unevaluable summaries will be 
presented as −, NA or NE.  
In listings, data will be sorted by site and patient, and when appropriate by visit or other 
identifiers for sequence or type of observation.  
4.3 
Subgroups 
Subgroup analyses will not be performed.  
4.4 
Multiple Comparison/Multiplicity 
No multiplicity adjustment is planned. 
 
5 
DEFINITIONS & DATA HANDLING CONVENTIONS 
5.1 
Study Day, Duration, and Study Periods  
Day 1 will be the date corresponding to the first administration of SRF617. Study Day will be 
computed as the given date minus the date of Day 1 +1 (i.e., Study Day = Date – Date of Day 
1 + 1) for dates on or after date of Day 1. For study assessment or treatment prior to Day 1, 
Study Day = Assessment Date – Date of Day 1. 
Unless otherwise specified, day is the primary time unit for derived time and durations. Derived 
time units include week=7 days, month=30.436875 days, and (Gregorian) year=365.2425 
days=12 months. Thus, 1 month and 4 weeks are considered different.  
Unless otherwise specified, duration of time is defined from the starting day through the ending 
day, inclusive of both boundary days. 
Study periods are defined as follows: 
• screening period: beginning on the day of informed consent, or Study Day -30, 
whichever is latest, and ending on Day -1.  
• treatment period: beginning on Study Day 1 and ending on the date of EoT visit. In case 
that the EoT visit is missed for any reason, the treatment period will end on the 7th day 
since the last dose of any study drug. 
• safety follow-up period: beginning on the first day after the treatment period and ending 
on the last day of the Safety Follow-up visit (or study discontinuation, whichever occurs 
first). Safety Follow-up visit is scheduled to be approximately 30 days after the last 
dose of SRF617, 30 days after the last dose of etrumadenant, or 90 days (+ 7 days) after 
the last dose of zimberelimab (30 days after the last dose of zimberelimab if the patient 
initiates a new anticancer therapy), whichever is latest. 
Unless otherwise specified, events in the screening period are considered as pre-treatment, and 
events in the treatment period or safety follow-up period are considered as on-treatment.  
5.2 
Analysis Visit Windows 
Patient visits will be presented according to the nominal visit as obtained upon the eCRF. All 
values will be included in the patient data listings. 


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
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13 
 
5.3 
Data Derivation 
Baseline and Change from Baseline 
The baseline value is defined to be the last non-missing assessment prior to the first dose of 
SRF617. For assessments performed on Cycle 1 Day 1, if the time of the day is missing but 
scheduled time point is recorded as preinfusion or pre-dose, the assessment may be considered 
the baseline assessment for the respective study procedures. Unless otherwise specified, change 
from baseline (CFB) calculations for a treatment window assessment will be the applicable 
treatment window assessment minus the baseline assessment. If either the treatment window 
assessment value or the baseline value is/are missing, then CFB will be set to missing for 
descriptive analysis purposes, unless otherwise specified. 
5.4 
Missing Data 
5.4.1 Partial or Missing Dates and Time 
The missing component(s) of incomplete dates (e.g., start and/or stop dates of AE, concomitant 
medication) will be assumed as the most conservative value possible. In general, unless the 
available parts of the partial date preclude an AE to be treatment-emergent, the AE will be 
considered treatment-emergent; similarly, unless the available parts of the partial date preclude 
a medication to be concomitant, the medication will be considered as a concomitant 
medication. 
For example, if the start date has a missing day value, the first day of the month will be imputed 
for study day computations, etc. If day is missing for an end date, the last day of the month will 
be imputed. If the start date has a missing month value, the first month of the year will be 
imputed for study day computations, etc. If month is missing for an end date, the last month of 
the year will be imputed. For determination of treatment-emergent status, the start date will be 
imputed as the date of the first dose of study drug, unless there is clear evidence (through 
comparison of partial dates/times) to suggest otherwise. 
Date imputation will only be used for computational purposes such as treatment-emergent 
status, etc. Actual data values, as they appear in the original eCRFs, will be presented in the 
patient data listings. Non-monotone partial dates (e.g., day and month are non-missing but year 
is missing) need to be queried and resolved before DBL. 
5.4.2 Other Missing Values 
Every effort will be made to obtain required data at each scheduled evaluation from all patients 
who have been enrolled. In general, missing data will not be imputed and the data will be 
analyzed as they are recorded. 
 
6 
STUDY POPULATION, CONDUCT AND PATIENT DISPOSITION 
6.1 
Analysis Sets 
The number and percentage of patients in each analysis set as defined in Section 3 will be 
descriptively summarized using the enrolled analysis set. Corresponding data listing will be 
provided using the enrolled analysis set.  


 
Sponsor: Surface Oncology 
Protocol: SRF617-201 
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14 
 
6.2 
Patient Disposition 
The number and percentage of patients in the following categories will be descriptively 
summarized using the safety analysis set. 
• SRF617 treatment ongoing 
• SRF617 treatment discontinuation  
• Reason for SRF617 treatment discontinuation  
o Death 
o Adverse Events 
o Progressive Disease 
− RECIST Progression, only 
− Clinical Progression, only 
− PSA Progression, only 
− Any combinations of the above 
− Other Progression 
o Non-compliance with study protocol 
o Physician Decision 
o Study terminated by sponsor 
o Withdrawal by subject 
o Lost to follow-up 
o Other 
• Etrumadenant treatment ongoing 
• Etrumadenant treatment discontinuation  
• Reason for Etrumadenant treatment discontinuation  
o Death 
o Adverse Events 
o Progressive Disease 
− RECIST Progression, only 
− Clinical Progression, only 
− PSA Progression, only 
− Any combinations of the above 
− Other Progression 
o Non-compliance with study protocol 
o Physician Decision 
o Study terminated by sponsor 
o Withdrawal by subject 
o Lost to follow-up 
o Other 
• Zimberelimab treatment ongoing 
• Zimberelimab treatment discontinuation  
• Reason for Zimberelimab treatment discontinuation  
o Death 
o Adverse Events 
o Progressive Disease 
− RECIST Progression, only 
− Clinical Progression, only 


 
Sponsor: Surface Oncology 
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− PSA Progression, only 
− Any combinations of the above 
− Other Progression 
o Non-compliance with study protocol 
o Physician Decision 
o Study terminated by sponsor 
o Withdrawal by subject 
o Lost to follow-up 
o Other 
• Study ongoing 
• Study discontinuation  
• Reason for study discontinuation  
o Death 
o Adverse Events 
o Progressive Disease 
o Non-compliance with study protocol 
o Physician Decision 
o Study terminated by sponsor 
o Withdrawal by subject 
o Lost to follow-up 
o Completed Safety Follow up visit 
o Other 
Disposition of patients will be provided in a data listing using the safety analysis set. 
6.3 
Protocol Deviations 
Protocol Deviation Management Plan (PDMP) version: 3.0 dated on 03Mar2023 defined the 
study specific procedures and responsibilities for managing Protocol Deviations (PDvs).  The 
document listed the definition of Bioclinica Deviation Description and Deviation Area, as 
well the Deviation Category (major vs minor). Subject level protocol deviations will be 
documented in the Clinical Trial Management System (CTMS). Protocol Deviation Review 
meeting will review protocol listing for quality control.   
Major deviations (Important Protocol Deviation, IPD) from the clinical protocol may include 
(if assessed as), but are not limited to: 
• ICF/Subject Information  
• Ineligible Subject Enrolled  
• IMP Dose Error  
• IMP Other Error  
• Prohibited Medication  
• SAE or AESI Reporting Failure  
All protocol deviations (both major and minor) will be provided in a data listing for all 
treated patients.  
 


 
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7 
DEMOGRAPHICS AND BASLEINE CHARACTERISTICS 
7.1 
Demographics 
The following demographic characteristics will be descriptively summarized using the safety 
analysis set:   
• Sex at birth 
• Age (years, as reported in Demographics EDC)  
• Age (>= median vs. < median; and >= 70 years vs.  < 70 years) 
• Race (American Indian or Alaska Native, Asian, Black or African American, Native 
Hawaiian or other Pacific Islander, White, Unknown, Other, Not Reported) 
• Ethnicity (Hispanic or Latino, not Hispanic or Latino, not reported, unknown) 
• ECOG performance status (0, 1) 
• ALP at baseline (>= median vs.< median) 
• LDH at baseline (>= median vs.< median) 
Demographic characteristics will also be provided in a data listing using the safety analysis set. 
7.2 
Cancer History 
The following primary and metastatic cancer history characteristics will be summarized using 
the safety analysis set:  
• TNM stage at initial diagnosis  
o Pathological T category (T1, T2, T3a, T3b, T4, Unknown)  
o Regional lymph node N category (NX, N0, N1, Unknown) 
o Distant metastasis M category (cM0, cM1a, cM1b, cM1c, pM1a, pM1b, pM1c, 
Unknown) 
• Castrate-Resistant Status (Chemical, Surgical) 
• Gleason score at Diagnosis (6, 7, ≥8) 
• Type of Progression at Trial Entry  
o PSA only 
➢ Nadir PSA on last therapy (ng/ml)  
o Radiographic progression 
➢ Bone only  
➢ Bone with Nodal Disease 
➢ Nodal disease only 
➢ Visceral 
• Distribution of metastatic disease 
o Metastatic Site Type 
➢ Pelvic nodal  
➢ Extra-pelvic nodal 
➢ Bone 
➢ Visceral  
o  Volume  
➢ High (number of lesions ≥ 4)  
➢ Low (0 ≤ number of lesions ≤ 3) 
• PSA at baseline (>= median vs.< median) 
• Time since prostate cancer diagnosis (months), defined as time from the date of prostate 
cancer diagnosis to the date of first SRF617 dose 


 
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• Time since metastatic disease diagnosis (weeks), defined as time from the date of 
metastatic disease diagnosis to the date of first SRF617 dose 
• Time since castrate resistance (weeks), defined as time from the date the disease 
became castrate resistant to the date of first SRF617 dose 
• Mutation/genetic alteration analysis 
o Yes 
o No 
• MSI status and MMR status  
o MSI-H (microsatellite instability-high) 
o MSI-L (microsatellite instability-low) 
o MSS (microsatellite stable) 
o dMMR (mismatch repair deficient) 
➢ Due to MLH1  
➢ Due to MSH2  
➢ Due to MSH6 
➢ Due to PMS2 
o pMMR (mismatch repair proficient) 
• DNA Damage Repair (DDR) Alterations 
o ARD1A  
o ATM  
o BARD1 
o BRCA1  
o BRCA2  
o BRIP1  
o CDK12 
o CHEK2 
o FANCA 
o <insert all of Genes in the eCRF>  
o Other  
• TMB 
o ≤10  
o >10 
o Unknown 
• PD-L1 expression 
o Negative  
o Positive 
➢ n, mean, standard deviation, median, min, max 
➢ <1%, >=1% 
o Unknown 
Primary cancer history characteristics and tumor genomic alterations/protein expression will 
also be provided in a data listing using the safety analysis set. 
7.3 
Prior Systemic Cancer Therapies 
The following prior systemic anti-cancer therapy characteristics will be summarized 
descriptively using the safety analysis set:  
• Prior systemic anticancer therapies 
o Yes  


 
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o No 
• Lines of therapy  
o 0 
o 1 
o 2 
o ≥3 
o n, mean, standard deviation, median, min, max 
• Type of systemic therapy  
o Chemotherapy  
➢ Taxane therapy: Yes, No 
o Immunotherapy 
o Hormonal therapy: 
➢ Novel ASRI - androgen receptor antagonist 
➢ Novel ASRI - CYP17 inhibitor 
➢ GnRH analog or antagonist 
➢ Older general androgen receptor antagonist 
➢ Other 
o Targeted therapy 
o Other 
• Setting of therapy 
o Neoadjuvant 
o Adjuvant 
o Advanced/Metastatic 
o Palliative 
o Other 
• Disease state for which the latest therapy was given 
o Biochemical (PSA only) non-metastatic castrate sensitive 
o Biochemical (PSA only) non-metastatic castrate resistant 
o Metastatic castrate sensitive 
o Metastatic castrate resistant 
• Primary reason for stopping last line treatment  
o Treatment completed 
o Progressive Disease 
o Toxicity 
o Adverse Event 
o Other  
• PSA response across all prior systemic therapies  
o Sensitive 
o Resistant 
Prior systemic cancer therapy information will also be provided in a data listing using the safety 
analysis set. 
7.4 
Prior Radiation Therapies 
The following prior radiation therapy characteristics will be summarized descriptively using 
the safety analysis set. Number and percentage with  
• Any prior radiation therapy 


 
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• Total duration of prior radiation therapy (weeks): A subject may receive multiple 
courses of radiation therapies. The total duration is the sum of the duration of each 
course of radiation therapy.  
• Type of radiation: Brachytherapy, EBRT, IGRT, IMRT, Implanted radioisotopes, 
Proton-beam, Radium-223 chloride/alpharadin, Strontium-89, Samarium-153, Other 
radionuclide, Other: A subject may receive multiple types of radiation therapy. 
7.5 
Medical History 
The medical history will be coded using MedDRA 24.1. 
The number and percentage of patients with conditions coded to each primary system organ 
class (SOC) and preferred term (PT) will be summarized using the safety analysis set. If a 
patient has more than one medical condition within an SOC or PT, the patient will be counted 
only once for the respective SOC or PT. 
Data listings of all medical history records will be provided using safety analysis set.  
 
8 
PROTOCOL-REQUIRED DRUG EXPOSURE AND COMPLIANCE 
Safety analysis set will be used to summarize exposure and compliance. 
8.1 
Study Drug Exposure 
The dosing data for SRF617, Etrumadenant, and Zimberelimab will be summarized 
descriptively (n, mean, standard deviation, median, min, max) using the safety analysis set:  
• Total number of cycles started is defined as the maximum number of treatment cycles 
that a patient receives each drug  
• Cumulative dose (mg), including cycle 1, 2, 3, 4, and overall:   
o SRF617 (mg) is the sum of the ‘Actual dose administered’ that the patient receives 
across cycles as recorded in the Administration eCRF  
o Zimberelimab (mg) is the sum of the ‘Actual dose administered’ that the patient 
receives across cycles as recorded in the Administration eCRF  
o Etrumadenant (mg) is the sum of the ‘Actual dose administered’ that the patient 
receives across cycles as recorded in the Administration eCRF plus Sum of 
(Assigned Dose × (Number of Capsules Taken per day/Number of Capsules per 
Assigned Dose) ×(End Date - Start Date+1) in the Etrumadenant Diary 
Information eCRF 
• Total planned dose (mg), including cycle 1, 2, 3, 4, and overall: 
o SRF617 (mg) is the sum of the ‘Dose Level’ that the patient receives across cycles 
as recorded in the Administration eCRF  
o Zimberelimab (mg) is the sum of the ‘Dose Level’ that the patient receives across 
cycles as recorded in the Administration eCRF  
o Etrumadenant (mg) is the sum of the ‘Dose Level’ that the patient receives across 
cycles as recorded in the Administration eCRF plus Sum of (Assigned Dose × 
(End Date - Start Date+1) in the Etrumadenant Diary Information eCRF 
• Compliance is 100*(Total cumulative dose/ Total planned dose), including cycle 1, 2, 
3, 4, and overall 
• Actual dose intensity (mg/cycle): cumulative dose / number of cycles initiated 


 
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• Planned dose intensity (mg/cycle):  
o SRF617: The planned dose intensity is 1400 × 2 = 2800 mg/cycle. 
o Etrumadenant: The planned dose intensity is 150 × 28 = 4200 mg/cycle. 
o Zimberelimab: The planned dose intensity is 480 mg/cycle. 
• Relative dose intensity (%): 100 × (actual dose intensity / planned dose intensity) 
• Number of doses missing:  
o SRF617 is the total number not administered in the Administration eCRF  
o Zimberelimab is the total number not administered in the Administration eCRF  
• Number of patients with at least one dose missing for Etrumadenant 
• Number of infusions interrupted, for SRF617 and Zimberelimab only 
The number and percentage of patients with dose missing (not administrated), infusion 
interrupted, reasons for dose missing (COVID-19 Related, Other), reasons for infusion 
interrupted (Infusion Reaction, Adverse Event other than Infusion Reaction, Other) will be 
presented.  The number and percentage of patients with Relative dose intensity (<50%, ≥50% 
– <80%, ≥80% – <120%, and ≥120%) and Compliance (<50%, ≥50% – <80%, ≥80% – <120%, 
and ≥120%) will be presented. 
All dosing data and the above derived dosing parameters will also be presented in a data listing 
using the safety analysis set. 
 
9 
PRIOR AND CONCOMITANT THERAPIES 
Safety analysis set will be used to summarize prior and concomitant therapies. 
9.1 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using WHODrug-Global-B3 September 2021 
with Anatomical Therapeutic Chemical Classification System (ATC) and preferred 
names (PN). Prior medications include non-study drug medications that are ended before 
Day 1. Concomitant medications include non-study drug medications that are used on/after 
Day 1. 
The number and percentage of patients with prior medication or concomitant medications will 
be summarized by ATC level 2 category and preferred name (PN). If a patient received more 
than 1 drug within an ATC class or PN, the patient will be counted only once for this ATC 
class of PN. Prior and concomitant medications information will also be provided in a data 
listing. 
9.2 
Prior and Concomitant Procedures 
Prior and concomitant procedure information will be provided in a data listing. 
 
10 EFFICACY ANALYSIS 
The assessment of tumor response is based on PCWG3 criteria as well as RECIST v1.1 being 
evaluated by Investigators.  The summary will be presented using response-evaluable analysis 
set.  


 
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Assessment of response will be evaluated by computed tomography or magnetic resonance 
imaging of chest/abdomen/pelvis and bone scan every 12 weeks.  PSA assessment will be 
performed every cycle.  Patients should continue past PSA progression until clear radiologic 
progression or clinical progression (eg, symptomatic or physical deterioration in the absence 
of radiographic progression that meets PCWG3 criteria).  The overall PCWG3 criteria and 
RECIST v1.1 Response visit responses include Complete Response (CR), Partial Response 
(PR), Stable Disease (SD), Progressive Disease (PD), Non-CR/Non-PD, Not Evaluable (NE), 
Not Assessed (NA),  
10.1 Definitions of Efficacy-related Variables 
10.1.1 Best Overall Response  
The best overall response (BOR) will be derived from all of visit overall responses per patients, 
including CR, PR, SD, PD, NE. Initial assessment of CR or PR per PCWG3 criteria or RECIST 
v1.1 needs to be confirmed by a second scan performed at least 4 weeks later. Unconfirmed 
CR or PR will be categorized as SD. Non-CR/Non-PD will be considered as SD and NA will 
be considered as NE during derivation. The patients in response-evaluable analysis set without 
any visit overall response will be categorized as NE. RECIST 1.1 BOR and PCWG3 BOR will 
be derived separately. Disease assessments after the start of new anticancer therapy will be 
excluded from efficacy derivation. 
10.1.2 PSA50 Response  
PSA50 response (PSA50) is defined as a confirmed PSA decrease from Baseline of 50% or more 
based on 2 consecutive assessments measured 3 to 4 weeks apart.  PSA50 response rate is the 
proportion of patients with PSA50. 
10.1.3 Primary Composite Response Rate  
The primary composite response rate (PCRR) is defined as the proportion of patients achieving 
PSA50 and/or radiographic objective response of confirmed CR/PR measured using PCWG3 
criteria. 
10.1.4 Efficacy Endpoints Excluded from Analysis  
o Objective response rate (ORR),  
o Duration of primary composite response,  
o Duration of response,  
o Disease control rate,  
o radiographic progression-free survival,  
o time to radiographic progression,  
o PSA30 response, and  
o Time to PSA progression  
will not be summarized. 


 
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10.2 Analysis of Efficacy Variables 
10.2.1 Primary Composite Response Rate  
The point estimate (calculated as a sample proportion), and 80%- and 95%-exact (Clopper-
Pearson) two-sided binomial confidence intervals for the Primary Composite Response Rate 
will be presented, together with the number and percentage of subjects with each type of 
Composite Response.  
One-sided p value of Primary Composite Response Rate vs 10% will be calculated with exact 
test. 
 
11 SAFETY ANALYSES 
The Safety Lead-in Analysis will be based on the safety lead-in evaluable analysis set. All other 
safety analyses will be performed using safety analysis set.   
11.1 Adverse Events 
Adverse events (AE) will be coded using MedDRA 24.1 and graded according to the NCI-
CTCAE version 5.0.  
Summaries of AEs will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that 
emerges or worsens in the period from the first dose of study drug to 30 days after the last dose 
of SRF617, 30 days after the last dose of etrumadenant, or 90 days after the last dose of 
zimberelimab (30 days after the last dose of zimberelimab if the patient starts another 
anticancer therapy), whichever is latest. TEAE summaries will be presented by primary System 
Organ Class (SOC) and Preferred Term (PT). Although AEs may be reported more than once 
for a PT or a SOC in a patient, each patient will only be counted once within the SOC or PT. 
An overview of Treatment Emergent Adverse Events (TEAEs), including number and percent 
of patients who had any TEAE, TEAEs related to any drug, serious TEAEs, serious TEAEs 
related to any drug, TEAEs leading to any drug withdrawal, TEAEs leading to any drug 
interruption, TEAEs leading to any drug dose reduction, adverse events of special 
interest (AESIs), TEAEs ≥ grade 3 in severity, TEAEs related to any drug with grade ≥3, 
symptomatic skeletal events, and TEAEs leading to death will be presented. 
If the severity grade is missing, the severity of the event will be graded as severe (Grade 3). A 
TEAE will be categorized as ‘related’ to study drug if the relationship of ‘Possible’, ‘Probable’, 
‘Definite’ is selected.  If the relationship to study drug is missing, the event will be considered 
as related in the analysis.  
The number and percentage of patients with TEAEs will be given by primary SOC and by PT 
within each SOC for the following: 
• TEAEs  
• TEAEs related to any drug 
• TEAEs with grade 3 or higher 
• TEAEs related to any drug with grade 3 or higher 
• Serious TEAEs  
• Serious TEAEs related to any drug  
• TEAEs of Special interest 


 
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• TEAEs leading to any drug withdrawal  
• TEAEs leading to any drug interruption  
• TEAEs leading to any drug dose reduction  
• Symptomatic skeletal event 
• TEAEs leading to death 
AESIs are defined as thromboembolic events, e.g., DVT, pulmonary embolism, stroke, and 
myocardial infarction.  
Patient listings will be provided for all adverse events, serious TEAEs, TEAEs of special 
interest, Symptomatic skeletal event, infusion reaction TEAEs, TEAEs leading to treatment 
withdrawal, TEAEs leading to treatment interruption, and TEAEs leading to dose reduction, 
TEAEs leading to death. 
11.2 Deaths 
Death information will also be provided in a listing. 
11.3 Vital Signs and Body Measurements 
Vital signs and body measurements (including height, weight, temperature, systolic and 
diastolic blood pressure, heart rate, and respiratory rate) change from baseline, and percentage 
change from baseline (CFB) values will be summarized descriptively over time as described in 
Section 4.2.  
Vital signs information will also be provided in a data listing. 
11.4 Clinical Laboratory  
For lab values in the form of <x, ≤x, below lower quantification limit, etc., the value will be 
imputed as x/2 or half of the lower quantification limit for the purpose of numerical descriptive 
summary. For lab values in the form of >x, ≥x, above upper quantification limit, etc., the value 
will be imputed as x or upper quantification limit for the purpose of numerical descriptive 
summary. When such imputation occurs, footnotes will be presented to clarify the imputation 
rule. The original lab values will be presented in data listings.  
11.4.1 Hematology, coagulation, clinical chemistry, thyroid function tests, 
testosterone, PAP and PSA 
The Laboratory test value, change from baseline, and percentage change from baseline for 
continuous parameters over hematology tests, chemistry tests, coagulation tests, thyroid 
function tests, testosterone, PAP and PSA will be summarized using descriptive statistics (n, 
mean, SD, median, minimum, maximum) by visit. 
Shift of hematology tests, coagulation tests, and chemistry tests from baseline CTCAE grade 
to the worst postbaseline CTCAE grade will be presented. If a parameter includes both hypo- 
and hyper- CTCAE grade derivation, hypo- and hyper- will be tabulated separately.  If the 
baseline is not CTCAE gradable (e.g., AST increase), the baseline measurement will be 
categorized as low/normal/high according to reference ranges. The programmatic grading will 
be modified from the CTCAE by using numerical lab results only, ignoring any other grading 
conditions in the CTCAE, e.g., clinical symptoms or signs.  
Additionally, the liver function tests (AST, ALT, ALP, and Total Bilirubin (TBL)) will be 
summarized in the following categories: 


 
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• Aspartate Aminotransferase (AST)  
o >3 x ULN 
o >5 x ULN 
o >10 x ULN 
o >20 x ULN 
• Alanine Aminotransferase (ALT)  
o >3 x ULN 
o >5 x ULN 
o >10 x ULN 
o >20 x ULN 
• AST or ALT 
o >3 x ULN 
o >5 x ULN 
o >10 x ULN 
o >20 x ULN 
• Total Bilirubin (TBL)  
o >1.5 x ULN 
o >2 x ULN 
• Alkaline Phosphatase (ALP)  
o >1.5 x ULN 
o >2 x ULN 
• (AST or ALT) and TBL  
o AST or ALT > 3 x ULN and TBL > 1.5 x ULN 
o AST or ALT > 3 x ULN and TBL > 2 x ULN 
• (AST or ALT) and ALP and TBL  
o AST or ALT > 3 x ULN and ALP < 2 x ULN and TBL > 2 x ULN 
Laboratory hematology, chemistry, coagulation, thyroid function tests will be provided in data 
listings by patient.   
11.4.2 Urinalysis 
A data listing of all urinalysis tests will be provided.  
11.4.3 Serology 
HIV tests and hepatitis (anti-HCV antibody, HCV RNA, HBV DNA and HBV surface antigen) 
will be screened in the study and a data listing of all virology screening results will be provided.  
11.5 ECG 
QTcF Interval (msec) will be collected.  QTcF Interval value at baseline will be summarized 
using descriptive statistics (n, mean, standard deviation, median, minimum, and maximum)  
All ECG data (scheduled or unscheduled) will be displayed in a data listing. 
11.6 Eastern Cooperative Oncology Group (ECOG) Performance Status 
All ECOG scores will be provided in a data listing. 
 


 
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12 OTHER ANALYSES 
12.1 Pharmacokinetic and Pharmacokinetic/Pharmacodynamic analyses 
These analyses are not covered by this SAP and will be reported separately. 
12.2 Pharmacodynamic Analyses  
These analyses are not covered by this SAP and will be reported separately. 
12.3 Immunogenicity Analyses 
These analyses are not covered by this SAP and will be reported separately. 
 
13 INTERIM ANALYSES 
Because of early termination of the study without proceeding to Stage 2, the analysis at the end 
of Stage 1 will be considered as the final analysis.  
 
14 STATISTICAL ANALYSES FOR SAFETY MONITORING  
The safety monitoring in this study is not supported by any statistical analyses. 
 
15 REFERENCES 
1. ICH Harmonised Tripartite Guideline E9, Statistical Principles for Clinical Trials, 1998 
2. ICH Harmonised Tripartite Guideline E3, Structure and Content of Clinical Study Reports. 
1995 
3. ICH Harmonised Tripartite Guideline E6(R2), Guideline for Good Clinical Practice, 1996 
4. ICH guideline E2F, Note for guidance on development safety update reports, 
EMA/CHMP/ICH/309348/2008, September 2010  
5. Eisenhauer EA, Therasse P, Bogaerts J et al.  New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45:228-247. 
6. Paules, M., Casey, M., Williams, G., Swann, R. S., Murphy, P. S., Salazar, V. M. Therasse, 
P. (2011). Recommendations for capture, validation and summarisation of data from 
studies using RECIST. Eur J Cancer, 47, 697-701.