FibroGen, Inc. announced topline data from the Fortis Therapeutics-sponsored Phase 1 study of FG-3246 (also known as FOR46), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with an MMAE-containing payload, in a dose-escalation and dose-expansion trial enrolling patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors have progressed on at least one androgen receptor-signaling inhibitor (ARSI). In the Phase 1 dose-escalation portion of the study, ascending dose levels of FG-3246 were administered every 3 weeks. In the dose-expansion arm of the trial, patients were treated at the 2.7 mg/kg adjusted body weight dosing (AjBW) until disease progression.

The endpoints were safety, tolerability, and anti-tumor activity as measured by the decline of prostate-specific antigen (PSA) from baseline, objective tumor response rate in patients with measurable disease, and radiographic progression free survival (rPFS). The completed Phase 1 trial includes a total of 56 patients from the dose-escalation and dose-expansion cohorts. The efficacy analysis includes patients who received a starting dose of FG-3246 of = 1.2 mg/kg in the dose-escalation cohort, and patients who received 2.7 mg/kg AjBW with a histologic diagnosis of adenocarcinoma in the dose-expansion cohort.

Patients were heavily pre-treated, having received a median of 5 lines of therapy prior to receiving FG-3246. In the efficacy analysis, PSA reductions of = 50% were observed in 36% of PSA evaluable patients. For RECIST evaluable patients, 20% met the criteria of a partial response, or tumor reduction in size of = 30%, with a median duration of response of 7.5 months.

The median rPFS in this heavily pre-treated patient population was 8.7 months. The most frequent adverse events were consistent with other MMAE-based ADCs and included infusion related reactions, fatigue, weight loss, neutropenia, and peripheral neuropathy. Earlier data from the FOR46-001 trial had been presented at the American Society for Clinical Oncology (ASCO) 2022 annual meeting1, and complete results from the study are being submitted to a medical journal for publication in 2024.