Study of SRF617 With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria:

* ≥ 18 years of age.
* Metastatic CRPC with castrate levels of testosterone (≤ 50 ng/dL or ≤ 1.7 nmol/L).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Progressed (by PSA or radiologic criteria) during or following treatment with a novel androgen receptor signaling inhibitor (ARSI, eg, abiraterone, enzalutamide, apalutamide, darolutamide), which may have been given for either hormone-sensitive prostate cancer or CRPC.
* 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).
* Progressed by PSA or radiologic criteria on or during last therapy for prostate cancer.
* 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.
* 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.
* Adequate renal function, defined as serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula.
* 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).
* Aspartate aminotransferase and alanine aminotransferase \< 2.5 × ULN (\< 5 × ULN if liver metastases present).
* 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.

Exclusion Criteria:

* 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.
* Any component of small cell or neuroendocrine histology.
* Previously received an anti-CD39 antibody, anti-CD39 targeted therapy, or other agent targeting the adenosine pathway.
* Prior treatment with programmed death-ligand 1 (PD-L1)/programmed death receptor-1 (PD-1) inhibitors.
* Prior treatment with ≥ 3 lines of taxane chemotherapy administered as a single agent or as part of a combination regimen.
* 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.
* Current pneumonitis with or without steroid requirement or history of pneumonitis requiring steroids.
* 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.
* Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
* 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.
* 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.
* Any gastrointestinal condition that would preclude the use of oral medications (eg, difficulty swallowing, nausea, vomiting, or malabsorption).