On May 15, 2025, the Food and Drug Administration approved retifanlimab-dlwr (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-dlwr, as a single agent, for adults with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.
Full prescribing information for Zynyz will be posted on Drugs@FDA.
Efficacy of retifanlimab-dlwr with carboplatin and paclitaxel was evaluated 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 AUC of 5 on Day 1, and paclitaxel 80 mg/m2 on Days 1, 8, and 15 for 6 cycles and were randomized (1:1) to receive 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 endpoint. Additional efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) as assessed by BICR. Median PFS was 9.3 months (95% 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-value 0.0006). Interim OS results were not statistically significant: median OS was 29.2 months (95% CI: 24.2, not estimable [NE]) and 23 months (95% CI: 15.1, 27.9) in the respective arms (hazard ratio 0.70 [95% CI: 0.49, 1.01]). Forty-five percent of patients who received placebo received 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. The major efficacy outcome measures were ORR and DOR as assessed by an independent review committee (IRC) according to RECIST v1.1. ORR was 14% (95% CI: 8, 23) and median DOR was 9.5 months (95% CI: 4.4, not estimable [NE]).
The prescribing information for retifanlimab-dlwr includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.
The recommended retifanlimab-dlwr dose in combination with carboplatin and paclitaxel is 500 mg every 4 weeks until disease progression, unacceptable toxicity, or up to 12 months. The recommended dose of retifanlimab-dlwr as a single agent is 500 mg every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. Refer to the prescribing information for carboplatin and paclitaxel for recommended dosing information in combination with retifanlimab.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Retifanlimab-dlwr was granted orphan drug designation for the treatment of anal cancer and this application was granted fast track designation and priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
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