- FG-3246 demonstrated efficacy in adenocarcinoma selected cohorts receiving biologically active doses of FG-3246 at ≥ 1.2 mg/kg in heavily pre-treated, biomarker unselected patients:
- Median radiographic progression free survival of 8.7 months
- PSA50 response in 36% of patients
- Confirmed radiographic objective response rate of 20%, with a median duration of response of 7.5 months
- FG-3246 demonstrated an acceptable safety profile; adverse events consistent with those observed in other antibody drug conjugate therapies with a MMAE payload
- Company plans to meet with the U.S. Food and Drug Administration (FDA) to discuss development pathway; Phase 2 initiation is anticipated in 2H 2024
“We are delighted to showcase the latest encouraging clinical data from the FOR46-001 Phase 1 ADC trial,” said Deyaa Adib, M.D., Chief Medical Officer of FibroGen. “We observed a median radiographic progression free survival of 8.7 months in heavily pre-treated patients, who received biologically active doses of FG-3246 in the second line or later setting prior to chemotherapy. These Phase 1 data provide evidence of a favorable safety profile and promising clinical activity as further evidenced by prostate-specific antigen reduction of ≥ 50% and shrinking of measurable disease. We look forward to publishing the totality of the Phase 1 data as we advance the program further in the clinic.”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.
“The results from the FOR46-001 Phase 1 study are promising, demonstrating a manageable safety profile and continued robust signals of clinical activity,” stated Dr. Rahul Aggarwal, Professor of Medicine at University of California San Francisco and Lead Investigator of the study. “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.”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.
Source: FibroGen, Inc. (2024). FibroGen Announces Topline Results from Phase 1 Monotherapy Study of FG-3246 in Patients with Metastatic Castration-Resistant Prostate Cancer [Press release]. https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-announces-topline-results-phase-1-monotherapy-study-fg.