FDA Officials Approve Retifanlimab-dlwr With Carboplatin and Paclitaxel and as Single Agent for Squamous Cell Carcinoma of Anal Canal

Both single-agent retifanlimab-dlwr (Zynyz; Incyte) and use with carboplatin and paclitaxel have been greenlit for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).¹

Researchers evaluated retifanlimab-dlwr in POD1UM-303/InterAACT 2 (NCT04472429), a randomized, multicenter, double-blind trial in 308 patients with chemotherapy-naïve inoperable locally recurrent or metastatic SCAC. Patients received carboplatin area under the curve of 5 on day 1, and paclitaxel 80 mg/m² on days 1, 8, and 15 for 6 cycles, and patients randomly received either retifanlimab-dlwr 500 mg intravenously every 4 weeks or placebo intravenously every 4 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 researchers noted that median PFS was 9.3 months (95% confidence interval [CI], 7.5-11.3) in the retifanlimab-dlwr arm and 7.4 months (95% CI, 7.1-7.7) in the placebo arm (hazard ratio, 0.63; 95% CI, 0.47-0.84; P=.0006). OS rates were not statistically significant, with median OS of 29.2 months and 23 months in the respective arms. Forty-five percent of patients who received placebo were administered retifanlimab-dlwr after disease progression. ORR was 56% (95% CI, 48-64) and 44% (95% CI, 36-52) in the respective arms.

Efficacy of retifanlimab-dlwr as a single agent was evaluated in POD1UM-202 (NCT03597295), an open-label, multicenter, 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-dlwr 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. ORR was 14% (95% CI, 8-23) and median DOR was 9.5 months (95% CI, 4.4-not estimable).

Reference

1. FDA. FDA approves retifanlimab-dlwr with carboplatin and paclitaxel and as a single agent for squamous cell carcinoma of the anal canal [press release]. May 15, 2025. Accessed July 1, 2025. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-retifanlimab-dlwr-carboplatin-and-paclitaxel-and-single-agent-squamous-cell-carcinoma