Multicenter phase 1, first-in-human study of FOR46 (FG-3246) for metastatic castration-resistant prostate cancer

FOR46, a fully human antibody conjugated to monomethyl auristatin E, targets a tumor-selective epitope of CD46, which is overexpressed in metastatic castration-resistant prostate cancer (mCRPC). A multicenter phase 1 trial in the USA evaluated FOR46 for progressive mCRPC in patients after treatment with one or more androgen signaling inhibitors. The most common grade ≥3 adverse events across all dose levels were neutropenia (59%), leukopenia (27%), lymphopenia (7%), anemia (7%), and fatigue (5%). One grade 3 febrile neutropenia event was observed. There were no treatment-related deaths. In the efficacy evaluable subset, the median radiographic progression-free survival was 8.7 monts (range 0.1-33.9). Fourteen of 39 evaluable patients (36%) achieved a PSA50 response. The confirmed objective response rate was 20%, with median duration of response 7.5 months. The authors conclude that FOR46 demonstrated encouraging preliminary clinical activity with a manageable safety profile.