The FDA has accepted a Biologics License Application for retifanlimab, an investigational intravenous PD-1 inhibitor, as a potential treatment for adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal who have progressed on or who are intolerant of platinum-based chemotherapy and has granted the BLA a Priority Review.
The FDA has accepted a Biologics License Application (BLA) for retifanlimab, an investigational intravenous PD-1 inhibitor, as a potential treatment for adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on or who are intolerant of platinum-based chemotherapy and has granted the BLA a Priority Review.1
A Prescription Drug User Fee Act target action date of July 25, 2021, was granted for review of the retifanlimab BLA.
“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,” said Lance Leopold, MD, group vice president, Immuno-Oncology Clinical Development, Incyte, in a statement. “Despite SCAC being a rare disease, its incidence is increasing, and its impact is profound. We look forward to working with the FDA to potentially fill an unmet need and advance progress in SCAC for patients.”
SCAC accounts for near 3% of digestive system cancers and is associated with human papillomavirus (HPV) and HIV infections. Currently, there are no FDA-approved treatments for patients who have progressed after frontline chemotherapy.
Data supporting the BLA come from the phase 2 POD1UM-202 trial (NCT03597295), in which retifanlimab induced durable responses in patients with previously treated patients with locally advanced or metastatic SCAC.
The single-arm, open-label, multicenter trial enrolled 94 patients with locally advanced or metastatic SCAC who had progressed on standard therapy. Patients with well-controlled HIV infection were eligible to enroll in the study if they had a CD4 count of ≥300/mcL, undetectable viral load, and if they were still receiving highly active antiretroviral therapy. Those with prior immunotherapy use, active autoimmune disease requiring systemic immunosuppression, known central nervous system metastases and/or carcinomatous meningitis, known active hepatitis, or active infections requiring systemic therapy were ineligible for enrollment.
Retifanlimab was administered intravenously at 500 mg once every 4 weeks.
The primary end point was overall response rate (ORR) and secondary end points were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events, and pharmacokinetics.
Patients had a median age of 64 years and the majority of patients were female (64.9%), White (76.6%), and had an ECOG performance status of 1 (58.5%). About three-fourths (73.4%) had received prior chemoradiotherapy, 17% had received radiotherapy alone, and 97% had received prior platinum. Thirty-nine patients (41.5%) had liver metastases and 9 (9.6%) were HIV-positive.2
The ORR by independent central review was 14% consisting of 1 complete response and 12 partial responses. An additional 35.1% had stable disease. The median DOR was 9.5 months (range, 5.6-not estimable). Responses were observed in patients regardless of PD-L1 expression, liver metastases, or HIV positivity.
The median PFS was 2.3 months (95% CI, 1.9-3.6) and the median OS was 10.1 months (95% CI, 7.9-not estimable). Responses were associated with a prolongation of PFS and OS.
Treatment with retifanlimab was well tolerated. Grade ≥3 treatment-related adverse events were reported in 11.7% of patients and grade ≥3 immune-related adverse events in 6.4%. The most common adverse events were fatigue and diarrhea. Only 2.1% of patients discontinued treatment due to an immune-related adverse event.1,2
The FDA also granted retifanlimab an orphan drug designation for the treatment of anal cancer.
A phase 3 trial (POD1UM-303/InterAACT 2; NCT04472429) has been opened to explore the combination of retifanlimab with carboplatin and paclitaxel in patients with inoperable locally recurrent or metastatic SCAC.