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

Prostate Cancer Clinical Trial

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

Status Recruiting

Clinical Trial 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 pathway inhibitor (ARPI) is more effective against prostate cancer than pembrolizumab + ARPI alone.

Clinical Trial 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 pathway inhibitor (ARPI) is more effective against prostate cancer than pembrolizumab and ARPI 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: ARPI (standard dosing schedule), pembrolizumab (400 mg every 6 weeks), 225Ac-J591 (single dose, either 65 or 90 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 + ARPI 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. 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). ;

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

• NCT number: NCT04946370
• Study type: Interventional
• Source: Weill Medical College of Cornell University
• Contact: GUONC Research Team
• Phone: 212-746-1480
• Email: guonc@med.cornell.edu
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 12, 2021
• Completion date: June 2028