ADC FG-3246 May Show Promise in Advanced Prostate Cancer

Findings from a preliminary trial evaluating a novel antibody-drug conjugate demonstrates benefits in patients with advanced prostate cancer.

Treatment with the antibody-drug conjugate (ADC) FG-3246 conferred what one researcher described as “promising” results for some patients with advanced prostate cancer.

Topline data has been released from a phase 1 study for patients with metastatic castration-resistant prostate cancer (mCDPC) whose tumors have progressed on at least one androgen receptor-signaling inhibitor (ARSI), according to an announcement from manufacturer FibroGen, Inc.

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“We are delighted to showcase the latest encouraging clinical data from the FOR46-001 Phase 1 ADC trial,” stated Dr. Deyaa Adib, chief medical officer of FibroGen, in a news release. “We observed a median radiographic progression-free survival [the time from treatment until new lesions are seen on scans] 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 [a protein which is associated with the presence of prostate cancer in the body] reduction of at least 50% [in 36% of evaluable patients] 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.”

Antibody-drug conjugates such as FG-3246, as defined by the National Cancer Institute, contain a monoclonal antibody that binds to a protein or a receptor on a cancer cell. It is chemically linked to a drug which then is designed to enter and kill the cancer cell without harming healthy cells.

Among evaluable patients, 20% experienced a reduction in tumor size of at least 30%, with a median duration of response of 7.5 months, according to the news release.

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“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 the University of California San Francisco and lead investigator of the study, in the news release. “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 [Xtandi (enzalutamide)] at the upcoming ASCO 2024 annual meeting.”

The phase 1 trial included 56 participants in its dose-escalation and dose-expansion cohorts, with patients having received a median of five lines of therapy previously. Complete results from the study, FibroGen reported, are being submitted to a medical journal for publication this year.

The most frequent side effects, FibroGen reported, included infusion-related reactions, fatigue, weight loss, neutropenia (a low count of neutrophils, a type of white blood cell) and peripheral neuropathy.

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