FibroGen, Inc. announced positive interim results from the dose escalation portion of the investigator-sponsored Phase 1b/2 study conducted by the University of California San Francisco of FG-3246 (FOR46), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with a MMAE-containing payload, in combination with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The presentation includes data from 17 biomarker unselected patients in the dose escalation portion of the trial. Eligibility criteria for the trial included patients who received at least one prior androgen receptor signaling inhibitor (ARSI) while patients who were treated with prior chemotherapy in the castration resistant setting were excluded.

Over 70% of the patients in the study received at least two prior ARSIs, which included prior enzalutamide treatment. Dose escalation was explored with and without prophylactic granulocyte colony-stimulating factor (G-CSF) support. The primary endpoint was determination of the maximally tolerated dose (MTD) of FG-3246 in combination with enzalutamide.

The combination treatment demonstrated an encouraging preliminary estimate of median radiographic progression free survival (rPFS) of 10.2 months. The MTD was established at 2.1 mg/kg ABW, with primary G-CSF prophylaxis, in combination with enzalutamide 160 mg/day. The most frequent adverse events were consistent with other MMAE-based ADCs and included fatigue, weight loss, elevated transaminases, neutropenia, and peripheral neuropathy.

Additionally, a baseline CD46-directed PET imaging probe utilizing the same antibody backbone as FG-3246 (89Zr-DFO-YS5) was obtained in a subset of patients and demonstrated tumor uptake in multiple lesions. This Phase 1b/2 study is an investigator-sponsored trial being conducted at the University of California San Francisco to evaluate FG-3246 (FOR46) in combination with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) after prior progression on at least one androgen receptor signaling inhibitor. The primary objective for the Phase 1b portion of the study is to determine the maximally tolerated dose (MTD) and recommended Phase 2 dose of FG-3246 in combination with enzalutamide in patients with mCRPC.

The objectives of the Phase 2 portion of the study are to determine the composite response rate (CRR), proportion of participants with a greater than or equal to 50% change in prostate specific antigen (PSA50), objective response rate (ORR), median duration of response, median radiographic progression free survival (rPFS), and median overall survival (OS) of patients treated with FG-3246 in combination with enzalutamide.