study of srf617 with ab928 (etrumadenant) and ab122 (zimberelimab) in patients with metastatic castration resistant prostate cancer

Conditions: Metastatic Castration-resistant Prostate Cancer; Prostate Cancer

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).

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).

Eligibility criteria:
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).

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