FDA Approves Zynyz for Squamous Cell Carcinoma of the Anal Canal

The FDA approved retifanlimab (Zynyz, Incyte Corporation) with carboplatin and paclitaxel for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The FDA also approved retifanlimab, as a single agent, for adults with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.

The efficacy of retifanlimab with carboplatin and paclitaxel was evaluated in POD1UM-303/InterAACT 2 (ClinicalTrials.gov Identifier: NCT04472429), a multicenter, randomized, double-blind trial in 308 patients with chemotherapy-naive, inoperable, locally recurrent or metastatic SCAC. Patients received carboplatin AUC of 5 on day 1, and paclitaxel 80 mg/m² on days 1, 8 and 15 for six cycles, and were randomized (1:1) to receive either:
• retifanlimab 500 mg IV every four weeks, or
• placebo intravenously every four weeks. 

The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) according to RECIST v1.1. Overall survival (OS) was a key secondary end point. Additional efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) as assessed by BICR. 

The median PFS was 9.3 months (95% CI, 7.5-11.3 months) in the retifanlimab arm and 7.4 months (95% CI, 7.1-7.7 months) in the placebo arm (hazard ratio, 0.63; 95% CI, 0.47-0.84; P=0.0006). Interim OS results were not statistically significant: The median OS was 29.2 months (95% CI, 24.2-not estimable [NE]) and 23 months (95% CI, 15.1-27.9 months) in the respective arms (hazard ratio, 0.70; 95% CI, 0.49-1.01). Of the patients who received placebo, 45% received retifanlimab after disease progression. The ORR was 56% (95% CI, 48%-64%) and 44% (95% CI, 36%-52%) in the respective arms.

The efficacy of retifanlimab as a single agent was evaluated in POD1UM-202 (NCT03597295), a multicenter, open-label, single-arm trial in 94 patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. Patients received retifanlimab 500 mg IV every four weeks until disease progression, unacceptable toxicity or up to 24 months. The major efficacy outcome measures were ORR and DOR as assessed by an independent review committee (IRC) according to RECIST v1.1. 

The ORR was 14% (95% CI, 8%-23%) and median DOR was 9.5 months (95% CI, 4.4-NE).

The prescribing information for retifanlimab includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT and embryo-fetal toxicity.

The full prescribing information for retifanlimab will be posted on Drugs@FDA.

Originally published by our sister publication Clinical Oncology News

—GEN Staff

Based on a press release from the FDA.