NCT04946370

Phase I/II Trial of Pembrolizumab and Androgen-receptor Inhibitor With or Without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: Weill Medical College of Cornell University · Academic / Other
• Sex: Male
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I/II study investigating the combination of 225Ac-J591 (a drug that can deliver radiation to prostate cancer cells) with pembrolizumab (immunotherapy, a drug that increases the immune system's ability to destroy cancer cells). This study will assess whether 225Ac-J591 + pembrolizumab + androgen receptor inhibitor (ARI) is more effective against prostate cancer than pembrolizumab + ARI alone.

Detailed description

This clinical trial is for men with progressive metastatic castration-resistant prostate cancer (mCRPC). The primary objectives of the study are to determine the optimal dose of 225Ac-J591 when combined with pembrolizumab (phase I) and then to assess whether the combination of 225Ac-J591, pembrolizumab, and androgen receptor inhibitor (ARI) is more effective against prostate cancer than pembrolizumab and ARI alone. 225Ac-J591 is a radionuclide conjugate involving Actinium-225 linked to J591, an antibody that recognizes prostate-specific membrane antigen (PSMA) on the surface of cancer cells; 225Ac-J591 is able to deliver powerful radiation to cancer cells. Pembrolizumab is a drug that strengthens the body's immune response to cancer cells. In the phase I portion of the study, two cohorts of up to 6 patients each will receive combined therapy: ARI (standard dosing schedule), pembrolizumab (400 mg every 6 weeks), 225Ac-J591 (single dose, either 65 or 80 KBq/kg). Following a minimum of 12 weeks of safety follow-up, the study team will determine which 225Ac-J591 dose is better. In the phase II portion, patients will be randomized to pembrolizumab + ARI with or without 225Ac-J591. The primary endpoint for phase II will be response - a composite of PSA, circulating tumor cell (CTC) count and imaging changes, comparing baseline and Week 12 measurements. Patients who achieve at least one of the criteria will be considered responders. Imaging (CT scan, bone scan) will occur every 12 weeks. Additionally, participants will undergo 68Ga-PSMA-11 PET/CT scan prior to therapy and at 12 weeks. Patients are able to receive pembrolizumab every 6 weeks for maximum 18 cycles (approximately 2 years).

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	225Ac-J591	Alpha-emitter Actinium-225 conjugated to the anti-PSMA antibody J591.
DRUG	Pembrolizumab	Pembrolizumab will be administered intravenously, 400mg every 6 weeks. Patients may receive maximum 18 cycles of therapy, approximately 2 years.
DRUG	Androgen receptor inhibitor	Patients will receive an oral androgen receptor inhibitor (ARI). Examples include enzalutamide, apalutamide, darolutamide. Dosing will be the standard dosing, as described by the package insert.
DIAGNOSTIC_TEST	68Ga-PSMA-11	\[185 ±74 MBq or 5 ±2 mCi\] intravenous during screening and 12 weeks. Imaging agent for PSMA PET/CT.

Timeline

• Start date: 2021-08-12
• Primary completion: 2027-10-01
• Completion: 2029-12-01
• First posted: 2021-06-30
• Last updated: 2026-02-03

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study