Retifanlimab Under FDA Priority Review for Advanced Anal Canal Cancer

Retifanlimab Under FDA Priority Review for Advanced Anal Canal Cancer

Retifanlimab is under review in the U.S. as a treatment for advanced squamous cell carcinoma of the anal canal (SCAC), a rare cancer of the digestive system, in adults who are unable to receive, or whose disease progressed after, initial platinum-based chemotherapy.

Incyte’s biologics licence application (BLA) to the U.S. Food and Drug Administration (FDA) was granted priority review status, which is expected to shorten the regulatory review from the standard 10 months to six months. A decision is expected by July 25.

“Patients with SCAC who have progressed after first-line chemotherapy treatment currently have no approved treatments available, and we are encouraged that the FDA’s acceptance of this BLA for priority review brings us one step closer to addressing this historically neglected, yet important, tumor,” Lance Leopold, MD, group vice president of immuno-oncology clinical development at Incyte, said in a press release.

SCAC is a rare cancer associated with infections by the human papillomavirus and human immunodeficiency virus (HIV), which are known to put patients at greater risk of certain cancers. Currently, the only treatment available for patients with advanced SCAC is first-line chemotherapy.

Retifanlimab, originally developed by MacroGenics and licensed to Incyte in 2017, belongs to a class of immunotherapies known as immune checkpoint inhibitors. It is designed to bind and block the activity of a protein receptor, called PD-1, found on the surface of immune cells that is often hijacked by cancer cells to dampen immune responses.

Inhibitors of this immune evasion mechanism are widely used in cancer therapeutics to help the immune system recognize and attack cancer cells.

The ongoing POD1UM-202 Phase 2 clinical trial (NCT03597295), which provided the basis for the priority review status, was designed to investigate retifanlimab in people with locally advanced or metastatic SCAC who progressed after or were unable to receive their initial chemotherapy regimen.

A total of 94 participants were enrolled, including nine (9.6%) with well-controlled HIV infection and 39 (41.5%) with liver metastasis. Their median age was 64 years, and most were female (64.9%) and white (76.6%).

All received a 500 mg dose of retifanlimab, given as an intravenous (into-the-vein) infusion every four weeks and, at the time of the last analysis, had been followed for a median of seven months.

Results showed that 14% of patients responded to treatment, including one complete response, and that an additional 35.1% attained stable disease after receiving retifanlimab. The median duration of response was 9.5 months.

Notably, these responses were independent of a patient’s PD-L1 status — usually, greater PD-L1 levels are associated with better responses to PD-1 and PD-L1 inhibitors — the presence of liver metastasis, or HIV infection.

Participants in the trial lived without disease progression for a median of 2.3 months, and their overall survival was a median of 10.1 months. But those who responded to treatment had markedly better survival outcomes, the researchers noted.

Also, the treatment was well-tolerated, even in patients with HIV infections, with a safety profile similar to that expected for a PD-1 inhibitor. A total of 6.4% of patients experienced serious immune-related adverse events, and 2.1% of discontinued treatment due to such side effects.

“Despite SCAC being a rare disease, its incidence is increasing and its impact is profound,” said Leopold. “We look forward to working with the FDA to potentially fill an unmet need and advance progress in SCAC for patients.”

An ongoing Phase 3 trial, called POD1UM-303 (NCT04472429), is now investigating a combination of retifanlimab plus chemotherapy to treat advanced SCAC patients who have not received prior chemo.

A total of 300 adult patients are being recruited at six sites in the U.S., and will be randomly assigned to receive retifanlimab, or a placebo, plus first-line platinum-based chemotherapy.

The main goal is to determine if the addition of retifanlimab to initial chemotherapy significantly extends the time patients live without signs of disease progression. Secondary measures include survival, response rate, duration of responses, and safety.

Retifanlimab is also being investigated across multiple cancer types, including endometrial cancer, Merkel cell carcinoma (a form of skin cancer), and lung cancer.