In a phase I study reported in the Journal of Clinical Oncology, Aggarwal et al reported activity with the antibody-drug conjugate (ADC) FOR46 in patients with metastatic castration-resistant prostate cancer. As stated by the investigators, “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.”
Study Details
In the U.S. multicenter dose-escalation/-expansion study, 56 patients enrolled between February 2019 and April 2022 received FOR46 at a starting dose of 0.1 mg/kg every 3 weeks. The primary objective of the trial was to determine the maximum tolerated dose (MTD).
Key Findings
Dose-limiting toxicities included neutropenia (n = 4), febrile neutropenia (n = 1), and fatigue (n = 1). The MTD was determined to be 2.7 mg/kg. The most common grade ≥ 3 adverse events across all dose levels were neutropenia (occurring in 59% of patients), leukopenia (27%), lymphopenia (7%), anemia (7%), and fatigue (5%). No treatment-related deaths were observed.
In the efficacy-evaluable subset of 40 patients treated with a starting dose of ≥ 1.2 mg/kg every 3 weeks, median radiographic progression–free survival was 8.7 months (range = 0.1–33.9 months). Among 39 evaluable patients, 14 (36%) achieved a prostate-specific antigen response of 50% reduction from baseline. Among 25 Response Evaluation Criteria in Solid Tumors–evaluable patients, confirmed objective response was observed in 5 (20%), with a median response duration of 7.5 months. Responders exhibited significantly higher on-treatment frequencies of circulating effector CD81 T cells.
The investigators concluded, “FOR46 demonstrated encouraging preliminary clinical activity with a manageable safety profile. Targeting CD46 elicited an immune priming effect that was associated with clinical outcomes.”
Rahul R. Aggarwal, MD, of the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a grant from the National Institutes of Health. For full disclosures of the study authors, visit ascopubs.org.
