AB-3028 programmable circuit T-cell therapy for metastatic castration-resistant prostate cancer

An Open-label, Multicenter Phase 1/2 Study to Evaluate the Safety and Efficacy of AB-3028 in Patients With Castration Resistant Prostate Cancer (CRPC)

This trial tests whether AB-3028, a programmable T-cell therapy made from your own cells, is safe and can help people with metastatic castration-resistant prostate cancer whose disease progressed after an androgen receptor pathway inhibitor.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 190 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Arsenal Biosciences, Inc. (Industry-sponsored)
• Locations: 7 sites (Duarte, California and 6 other locations)
• Trial ID: NCT07285694 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter Phase 1/2 trial gives a single intravenous infusion of autologous T cells that have been engineered with a DNA cassette to recognize both a priming antigen and PSMA on prostate cancer cells using a logic-gated design. The Phase 1 portion determines safety and the maximum tolerated or recommended Phase 2 dose, while the Phase 2 portion measures clinical activity against metastatic castration-resistant prostate cancer. Eligible participants must be PSMA-positive by PET and have progressed after at least one novel androgen receptor pathway inhibitor. Subjects are followed with serial safety checks and tumor response assessments after treatment.

Who should consider this trial

Good fit: Adults with histologically confirmed metastatic castration-resistant prostate cancer who are PSMA-positive by PET, have progressed after at least one androgen receptor pathway inhibitor, have measurable or evaluable disease and adequate organ function, and can undergo leukapheresis and extended monitoring are the intended candidates.

Not a fit: Patients without PSMA expression, with active central nervous system metastases or leptomeningeal disease, those who recently received systemic CRPC therapy within 14 days before leukapheresis, or who cannot undergo leukapheresis or required monitoring are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, AB-3028 could direct the immune system to more specifically kill PSMA-positive prostate cancer cells while reducing damage to normal tissues, potentially controlling disease in patients with limited options.

How similar studies have performed: PSMA-targeted and CAR-T approaches in prostate cancer have shown limited but promising signals in early trials, while programmable logic-gated T cells are a relatively novel approach with encouraging preclinical and early-phase data but not yet proven in large trials.

Eligibility criteria

Key Inclusion Criteria:

1. At least 18 years of age at time of signing informed consent form.
2. Histologically confirmed adenocarcinoma of the prostate, meeting all of the following criteria:

   • Documented progressive metastatic castration-resistant prostate cancer (mCRPC) based on PCWG3 criteria.
3. Prior prostate cancer treatment with at least 1 novel androgen receptor pathway inhibitor (ARPI) therapy.

   • PSMA+ by PSMA PET.
   * Measurable disease by RECIST 1.1 criteria, or evaluable disease via measurable PSA (≥ 1 ng/mL) per PCWG3 criteria.
4. Adequate organ functions.

Key Exclusion Criteria:

1. Any prior systemic therapy for CRPC within 14 days prior to scheduled protocol required leukapheresis.
2. Central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression.
3. Unwillingness to participate in an extended safety monitoring period.

Where this trial is running

Duarte, California and 6 other locations

• City of Hope — Duarte, California, United States (Recruiting)
• USC Norris Comprehensive Cancer Center — Los Angeles, California, United States (Recruiting)
• University of California, San Francisco — San Francisco, California, United States (Recruiting)
• University of Iowa and Holden Comprehensive Cancer Center — Iowa City, Iowa, United States (Recruiting)
• The University of Kansas Cancer Center — Fairway, Kansas, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Perlmutter Cancer Center - NYU Langone Health — New York, New York, United States (Recruiting)

Study contacts

• Study coordinator: Arsenal Biosciences, Inc.

Conditions Metastatic Castration Resistant Prostate Cancer; prostate cancer; metastatic; Programmable circuit T cell; CRPC; AB-3028; autologous Cell Therapy; Cell Therapy