FibroGen Presents Positive Phase 1b Data of FG-3246 with Enzalutamide in mCRPC at 2024 ASCO Meeting

FibroGen, Inc. has announced positive interim results for the combination therapy of FG-3246 and enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC). The data, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, indicates a median radiographic progression-free survival (rPFS) of 10.2 months in biomarker-unselected patients.

Dr. Deyaa Adib, Chief Medical Officer of FibroGen, expressed enthusiasm about the early efficacy signals observed. He noted that these results build on the promising activity seen in previous Phase 1 monotherapy trials and preclinical studies. The combination therapy showed enhanced tumor cytotoxic activity, and further data from ongoing collaborations with the University of California San Francisco (UCSF) is anticipated.

The dose escalation study involves 17 patients who had previously received at least one androgen receptor signaling inhibitor (ARSI). Exclusion criteria included prior chemotherapy in the castration-resistant setting. Over 70% of the participants had been treated with at least two prior ARSIs, including enzalutamide. The primary objective was to determine the maximally tolerated dose (MTD) of FG-3246 in combination with enzalutamide, which was established at 2.1 mg/kg every three weeks alongside the standard enzalutamide dose of 160 mg daily.

Adverse events were consistent with those typically seen in other MMAE-based antibody-drug conjugates (ADCs), including fatigue, weight loss, elevated transaminases, neutropenia, and peripheral neuropathy. Primary prophylactic granulocyte colony-stimulating factor (G-CSF) support was used in some cases.

Additionally, a subset of patients underwent baseline CD46-directed PET imaging using an antibody probe similar to FG-3246, which revealed tumor uptake in various lesions. Dr. Rahul Aggarwal, the study's Principal Investigator and Professor of Medicine at UCSF, highlighted the potential clinical benefits and favorable safety profile observed with the combination therapy. He emphasized the ongoing evaluation in the Phase 2 trial and the potential of the PET imaging probe as a predictive biomarker.

The trial's Phase 1b portion aimed to establish the MTD and recommended Phase 2 dose, while Phase 2 will assess composite response rates, PSA50, objective response rates, duration of response, rPFS, and overall survival. FG-3246 is being developed as a potential first-in-class fully human ADC targeting CD46, a receptor overexpressed in prostate cancer and other tumors. The drug, in-licensed from Fortis Therapeutics, combines an anti-CD46 antibody with the anti-mitotic agent MMAE.

FibroGen plans to discuss the development pathway for FG-3246 with the U.S. Food and Drug Administration (FDA) and aims to initiate a Phase 2 monotherapy trial in the second half of 2024. Their broader research portfolio includes potential treatments for various cancers, such as metastatic pancreatic cancer and anemia in chronic kidney disease.

FG-3246 remains investigational and is not yet approved for marketing by regulatory authorities. The company's research continues to focus on advancing novel therapies in cancer biology, with ongoing trials exploring the efficacy and safety of their drug candidates.