FDA approves retifanlimab-dlwr with carboplatin and paclitaxel and as a single agent for squamous cell carcinoma of the anal canal

Regulatory approval: On May 15, 2025, the FDA approved retifanlimab-dlwr (Zynyz) with carboplatin and paclitaxel for first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The FDA also approved retifanlimab-dlwr monotherapy for adults with locally recurrent or metastatic SCAC whose disease progressed on or who are intolerant to platinum-based chemotherapy. Approvals were supported by POD1UM-303/InterAACT 2 and POD1UM-202.

FDA approval (May 15, 2025): retifanlimab-dlwr in SCAC

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

Supporting evidence

  • POD1UM-303/InterAACT 2 (NCT04472429): randomized, multicenter, double-blind trial (n=308) in chemotherapy-naïve inoperable locally recurrent/metastatic SCAC. Patients received carboplatin (AUC 5 Day 1) + paclitaxel (80 mg/m² Days 1, 8, 15) for 6 cycles and were randomized to retifanlimab-dlwr 500 mg IV q4w vs placebo.
    • Median PFS (BICR, RECIST 1.1): 9.3 vs 7.4 months (HR 0.63; 95% CI 0.47–0.84; p=0.0006).
    • Interim OS: not statistically significant (median 29.2 vs 23.0 months; HR 0.70; 95% CI 0.49–1.01); 45% of placebo patients crossed over to retifanlimab-dlwr.
    • ORR: 56% vs 44%.
  • POD1UM-202 (NCT03597295): open-label, single-arm trial (n=94) post-platinum progression/intolerance.
    • ORR (IRC): 14% (95% CI 8–23); median DOR: 9.5 months (95% CI 4.4–NE).

Label highlights

Warnings/precautions include severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity. Recommended dosing: 500 mg IV q4w (combo up to 12 months; monotherapy up to 24 months).

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