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

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase 2 Trial of SRF617 in Combination With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Metastatic Castration-resistant Prostate Cancer, Prostate Cancer

Intervention / Treatment
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* Drug: SRF617
* Drug: etrumadenant
* Drug: zimberelimab


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SRF617 in combination with etrumadenant and zimberelimab<br>All patients will receive SRF617 administered in combination with etrumadenant (AB928) and zimberelimab (AB122). | Drug: SRF617<br>* SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39.<br>Drug: etrumadenant<br>* Etrumadenant is an A2aR and A2bR antagonist.<br>* Other names: AB928;Drug: zimberelimab<br>* Zimberelimab is a fully human anti-PD-1 monoclonal antibody.<br>* Other names: AB122;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with an objective PSA (prostate-specific antigen) or radiologic response per PCWG3 criteria | 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 | Up to 24 months | 
| Incidence and severity of adverse events (AEs) based on treatment-emergent AEs (TEAEs) | Incidence and severity of adverse events (AEs) 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 | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Assessed radiographically by PCWG3 criteria and RECIST v1.1 | Up to 24 months | 
| Duration of response (DOR) | Time from 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 | Up to 24 months | 
| Disease control rate (DCR) | Percentage of patients with complete response (PR), partial response (PR), or stable disease lasting a minimum of 12 weeks | Up to 24 months | 
| PSA50 response | Confirmed PSA decrease from Baseline of 50% or more | Up to 24 months | 
| PSA decline | Changes in PSA across the trial period | Up to 24 months | 
| Time to PSA progression | Changes in PSA across the trial period | Up to 24 months | 
| Radiographic progression free survival (PFS) | PFS is 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 | Up to 24 months | 
| Landmark PFS | 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 | Up to 24 months | 
| Maximum observed serum concentration of SRF617 (Cmax) | Serum samples will be collected and analyzed to assess the Cmax of SRF617 | Up to 24 months | 
| Minimum observed serum concentration of SRF617 prior to administration of subsequent dose (Cmin) | Serum samples will be collected and analyzed to assess the Cmin of SRF617 | Up to 24 months | 
| Antidrug Antibodies (ADAs) | Percentage of patients with ADAs to SRF617 | Up to 24 months | 
| Symptomatic Skeletal Events (SSEs) | Incidence of SSEs per PCWG3 criteria | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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