Phase 2 clinical trial is starting to enroll patients to further evaluate FG-3246 (FOR46), a novel antibody-drug conjugate targeting CD46, in metastatic castration-resistant prostate cancer (mCRPC). The study, registered under ClinicalTrials.gov (NCT06842498), aims to enroll approximately 75 patients who have previously been treated with one second-generation androgen receptor signaling inhibitor (ARSI) but have not received prior taxane therapy in the castration-resistant setting. The trial will assess key efficacy measures, including prostate-specific antigen (PSA) decline, objective response rate, radiographic progression-free survival, and overall survival.

This new trial builds on promising findings from a Phase 1b study, presented at the 2024 ASCO Annual Meeting, which evaluated FG-3246 in combination with enzalutamide. Conducted at the University of California San Francisco, the study enrolled 17 patients who had progressed after at least one ARSI. More than 70% had received at least two prior ARSIs, including enzalutamide, though patients previously treated with chemotherapy in the mCRPC setting were excluded. The primary objective was to establish the maximally tolerated dose.

The results were encouraging, with the combination therapy demonstrating a median radiographic progression-free survival of 10.2 months in biomarker-unselected patients. The safety profile was consistent with other MMAE-based antibody-drug conjugates, with side effects including fatigue, weight loss, elevated liver enzymes, neutropenia, and peripheral neuropathy. Some patients required primary prophylactic granulocyte colony-stimulating factor (G-CSF) support to manage neutropenia.

If the study confirms the efficacy signals observed in the earlier trial, FG-3246 could represent a new avenue for patients who have exhausted current AR-targeting therapies.

Clinical trial.