FDA Approves Retifanlimab Combo and Solo Use for Anal Canal Squamous Cell Carcinoma

On May 15, 2025, the Food and Drug Administration (FDA) announced the approval of retifanlimab-dlwr, marketed as Zynyz by Incyte Corporation, in combination with carboplatin and paclitaxel. This drug regimen is designed for initial treatment of adults with inoperable, locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). Additionally, retifanlimab-dlwr has been approved as a standalone treatment for patients whose disease has progressed or who cannot tolerate platinum-based chemotherapy. Comprehensive prescribing details for Zynyz will be available through Drugs@FDA.

The effectiveness of retifanlimab-dlwr in combination with carboplatin and paclitaxel was tested in the POD1UM-303/InterAACT 2 clinical trial (NCT04472429). This double-blind, randomized, multicenter study involved 308 participants suffering from chemotherapy-naïve inoperable, locally recurrent or metastatic SCAC. Within the trial, participants received carboplatin AUC of 5 on Day 1, along with paclitaxel dosed at 80 mg/m2 on Days 1, 8, and 15 across six cycles. They were randomly assigned to receive either retifanlimab-dlwr at 500 mg intravenously every four weeks or a placebo via intravenous administration with the same frequency.

The principal measure of efficacy was progression-free survival (PFS), evaluated by an independent central review using RECIST v1.1 standards. Overall survival (OS) was a crucial secondary outcome. Other efficacy indicators included overall response rate (ORR) and duration of response (DOR), both assessed by blinded independent central review. Results showed a median PFS of 9.3 months in the retifanlimab-dlwr group compared to 7.4 months in the placebo group, with a hazard ratio of 0.63 and a significant p-value of 0.0006. Interim OS findings were not statistically remarkable, showing a median OS of 29.2 months for the treatment group versus 23 months for the placebo group. Notably, 45% of placebo recipients switched to retifanlimab-dlwr after their disease progressed. ORR was 56% in the retifanlimab-dlwr arm and 44% in the placebo group.

The efficacy of retifanlimab-dlwr as a monotherapy was explored in the POD1UM-202 study (NCT03597295), an open-label, multicenter, single-arm trial with 94 patients experiencing locally recurrent or metastatic SCAC after platinum-based chemotherapy failure. These patients received retifanlimab-dlwr at 500 mg intravenously every four weeks until progression, intolerable side effects, or a maximum duration of 24 months. ORR and DOR were the primary efficacy outcomes, assessed by an independent review committee per RECIST v1.1. The ORR observed was 14%, with a median DOR of 9.5 months.

The prescribing information for retifanlimab-dlwr outlines warnings for severe and potentially fatal immune-mediated adverse reactions, infusion-related complications, risks associated with allogeneic HSCT, and embryo-fetal toxicity. The recommended dosage of retifanlimab-dlwr, when used in conjunction with carboplatin and paclitaxel, is 500 mg every four weeks until disease advancement, unacceptable side effects, or a maximum of 12 months. As a single agent, it is advised at the same dose every four weeks until progression, intolerable side effects, or up to 24 months. Specific dosing recommendations for carboplatin and paclitaxel in combination with retifanlimab can be found in their respective prescribing information.

This review was facilitated by the Assessment Aid, a voluntary submission aimed at streamlining the FDA's evaluation process. Retifanlimab-dlwr received orphan drug designation for anal cancer treatment and was granted fast track designation with priority review status.