22 January 2021 - - The US Food and Drug Administration has accepted for Priority Review US-based Incyte's (NASDAQ: INCY) Biologics License Application for retifanlimab, an 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, the company said.

The BLA submission is based on data from the Phase 2 POD1UM-202 trial evaluating retifanlimab in previously treated patients with locally advanced or metastatic SCAC who have progressed on, or are intolerant of, standard platinum-based chemotherapy.

The trial enrolled 94 patients, including several with well-controlled human immunodeficiency virus infection.

The study, which was recently presented at the European Society for Medical Oncology Virtual Congress 2020, resulted in an objective response rate of 14% for retifanlimab monotherapy as determined by independent central review using RECIST v1.1.

Responses were observed regardless of PD-L1 status, presence of liver metastases, age or HIV+ status and were durable (median 9.5 months).

Treatment-related adverse events ≥Grade 3 occurred in 11.7% of patients. Immune-related adverse events ≥Grade 3 occurred in 6.4% of patients. The most common adverse reactions (incidence ≥ 20%) were fatigue and diarrhea.

Retifanlimab has been granted Orphan Drug Designation by the FDA for the treatment of anal cancer, along with Priority Review.

The FDA grants Priority Review to medicines that may offer a major advance in treatment where none currently exists.

This designation shortens the review period by four months as compared to Standard Review. The Prescription Drug User Fee Act (PDUFA) target action date for retifanlimab is July 25, 2021.

SCAC is associated with human papillomavirus and HIV infections and accounts for almost 3% of digestive system cancers.

Patients with metastatic SCAC have a poor five-year survival, and there are no FDA-approved treatments for patients who have progressed after first-line chemotherapy.

POD1UM-303/InterAACT 2 (NCT04472429), a Phase 3 trial of retifanlimab in combination with carboplatin and paclitaxel in patients with inoperable locally recurrent or metastatic SCAC, is now open and recruiting patients.

POD1UM-202 (NCT03597295) is an open-label, single-arm, multicenter, Phase 2 study evaluating retifanlimab in patients with squamous cell carcinoma of the anal canal who have progressed on, or who are intolerant of, platinum-based chemotherapy. Retifanlimab 500 mg is administered intravenously every 4 weeks.

The primary endpoint is objective response rate as determined by independent central review using RECIST v1.1. Secondary endpoints include additional measures of clinical benefit, duration of response, disease control rate, progression-free survival and overall survival; safety and pharmacokinetics.

The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-202, POD1UM-303 and several other Phase 1, 2 and 3 studies for patients with solid tumors including squamous cell carcinoma of the anal canal, microsatellite instability-high endometrial cancer, Merkel cell carcinoma and non-small cell lung cancer, among others.

Retifanlimab (formerly INCMGA0012), an investigational intravenous anti-PD1 antibody, is currently under evaluation in registration-directed trials as a monotherapy for patients with microsatellite instability-high endometrial cancer, Merkel cell carcinoma and squamous cell carcinoma of the anal canal; and in combination with platinum-based chemotherapy for patients with non-small cell lung cancer and SCAC.

Retifanlimab has been granted Orphan Drug Designation by the US Food and Drug Administration for the treatment of anal cancer.

In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab.

In 2019, Incyte and Zai Lab announced a collaboration and license agreement for the development and commercialization of retifanlimab in Greater China.

Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics.