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

Sponsor

Surface Oncology (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05177770

Collaborator

Arcus Biosciences, Inc. (Industry)

Enrollment

Locations

Arm

21.5

Anticipated Duration (Months)

5.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-resistant Prostate Cancer Prostate Cancer	Drug: SRF617 Drug: etrumadenant Drug: zimberelimab	Phase 2

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 17, 2022

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: SRF617 in combination with etrumadenant and zimberelimab

All patients will receive SRF617 administered in combination with etrumadenant (AB928) and zimberelimab (AB122).

Drug: SRF617

SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39.

Drug: etrumadenant

Etrumadenant is an A2aR and A2bR antagonist.

Other Names:

AB928

Drug: zimberelimab

Zimberelimab is a fully human anti-PD-1 monoclonal antibody.

Other Names:

AB122

Outcome Measures

Primary Outcome Measures

The proportion of patients with an objective PSA (prostate-specific antigen) or radiologic response per PCWG3 criteria [Up to 24 months]
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 adverse events (AEs) based on treatment-emergent AEs (TEAEs) [Up to 24 months]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
2	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
3	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	84119
4	UT Southwestern	Dallas	Texas	United States	75390
5	START South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas	United States	78229
6	START Mountain Region, Utah Cancer Specialists	West Valley City	Utah	United States	84119
7	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109