FG-3246 shows initial promise in mCRPC

FG-3246 (FOR46), an antibody drug conjugate (ADC) targeted against CD46, demonstrated safety and preliminary efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors progressed on at least 1 androgen receptor-signaling inhibitor, according to topline data from the phase 1 FOR46-001 trial (NCT03575819) published in a news release from FibroGen, Inc, the developer of the ADC.¹

The investigators plan to initiate the phase 2 portion of the study in the second half of 2024.

Overall, data from the study showed that 36% of evaluable patients experienced at least a 50% reduction in prostate-specific antigen (PSA) levels from baseline. Among RECIST-evaluable patients, 20% demonstrated a partial response or a reduction in tumor size of at least 30%. The median duration of response was 7.5 months.

Among all patients, the median radiographic progression-free survival (rPFS) was 8.7 months.

Regarding safety, the most common adverse events were infusion-related reactions, fatigue, weight loss, neutropenia, and peripheral neuropathy. The safety profile was consistent with other monomethyl auristatin E-based ADCs.

“The results from the FOR46-001 phase 1 study are promising, demonstrating a manageable safety profile and continued robust signals of clinical activity,” said principal investigator Rahul Aggarwal, MD, professor of medicine at the University of California, San Francisco, in the news release.¹ “The observed median radiographic progression-free survival of 8.7 months in patients treated with a starting FG-3246 dose of 1.2 mg/kg and higher is quite favorable and highlights the therapeutic potential of FG-3246 as a new ADC aimed at a novel target. These findings warrant further investigation and hold promise for addressing the therapeutic needs of patients with CD46 positive prostate cancer. We are also excited about potential combinations with FG-3246 and will be presenting investigator sponsored trial data of FG-3246 in combination with enzalutamide at the upcoming ASCO 2024 annual meeting.”

In total, the FOR46-001 trial enrolled 56 heavily pretreated patients with mCRPC across both the dose-escalation and dose-expansion cohorts. Patients included in the trial had received a median of 5 lines of therapy before treatment with FG-3246.

The dose-escalation cohort included 33 patients who received ascending doses of IV-administered FG-3246 between 0.1 mg/kg and 3.0 mg/kg every 3 weeks. Adjusted body weight dosing (AjBW) was used at most dose levels above 2.1 mg/kg.

The dose-expansion cohort enrolled 23 patients, 18 of whom had adenocarcinoma mCRPC and 5 of whom had neuroendocrine prostate cancer. All patients received FG-3246 at 2.7 mg/kg (maximum = 270 mg) with AjBW every 3 weeks until disease progression.

The efficacy analysis included patients who received FG-3246 at a starting dose of 1.2 mg/kg or higher in the dose-escalation cohort, and those patients who received 2.7 mg/kg AjBW with a histological diagnosis of adenocarcinoma in the dose-expansion cohort.

End points for the trial included safety, tolerability, and preliminary anti-tumor activity, as measured by decreases in PSA from baseline, objective tumor response rate in patients with measurable disease, and rPFS.²

The investigators plan to initiate the phase 2 portion of the study in the second half of 2024. FibroGen also announced plans to meet with the FDA to discuss a development pathway for FG-3246 in mCRPC.

References

1. FibroGen announces topline results from phase 1 monotherapy study of FG-3246 in patients with metastatic castration-resistant prostate cancer. News release. FibroGen, Inc. Published April 2, 2024. Accessed April 3, 2024. https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-announces-topline-results-phase-1-monotherapy-study-fg

2. A phase 1 study of FOR46 in patients with metastatic castration-resistant prostate cancer (mCRPC). ClinicalTrials.gov. Last updated February 1, 2024. https://clinicaltrials.gov/study/NCT03575819