The U.S. Food and Drug Administration (FDA) approved retifanlimab-dlwr (Zynyz), a PD-1–blocking monoclonal antibody, with carboplatin and paclitaxel for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal. The FDA also approved retifanlimab as a single agent for adults with locally recurrent or metastatic squamous cell carcinoma of the anal canal with disease progression on or intolerance to platinum-based chemotherapy. The indications were approved on May 15, 2025.
Combination Regimen: POD1UM-303/InterAACT 2
Efficacy of retifanlimab with carboplatin and paclitaxel was evaluated in POD1UM-303/InterAACT 2 (ClinicalTrials.gov identifier NCT04472429), a randomized, multicenter, double-blind trial in 308 patients with chemotherapy-naive, inoperable, locally recurrent or metastatic squamous cell carcinoma of the anal canal. All patients received carboplatin at AUC 5 on day 1; paclitaxel at 80 mg/m2 on days 1, 8, and 15 for six cycles. Patients were randomly assigned (1:1) to receive either retifanlimab at 500 mg intravenously every 4 weeks or placebo intravenously every 4 weeks.
The major efficacy outcome measure was progression-free survival, as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; overall survival was a key secondary endpoint. Additional efficacy outcome measures were overall response rate and duration of response, as assessed by blinded independent central review.
Median progression-free survival was 9.3 months (95% confidence interval [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 [HR] = 0.63, 95% CI = 0.47–0.84, P = .0006). Interim overall survival results were not statistically significant: median overall survival was 29.2 months (95% CI = 24.2 months to not estimable) and 23 months (95% CI = 15.1–27.9 months) in the respective arms (HR = 0.70, 95% CI = 0.49–1.01). A total of 45% of patients on placebo received retifanlimab after disease progression. The overall response rates were 56% (95% CI = 48%–64%) and 44% (95% CI = 36%–52%) in the respective arms.
Monotherapy: POD1UM-202
Efficacy of retifanlimab 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 squamous cell carcinoma of the anal canal with disease progression on or intolerance to platinum-based chemotherapy. Patients received retifanlimab at 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or for up to 24 months. The major efficacy outcome measures were overall response rate and duration of response, as assessed by an independent review committee according to RECIST v1.1.
The overall response rate was 14% (95% CI = 8%–23%). The median duration of response was 9.5 months (95% CI = 4.4 months to not estimable).
The recommended retifanlimab dose in combination with carboplatin and paclitaxel is 500 mg every 4 weeks until disease progression, unacceptable toxicity, or for up to 12 months. The recommended dose of retifanlimab as a single agent is 500 mg every 4 weeks until disease progression, unacceptable toxicity, or for up to 24 months. The prescribing information for retifanlimab includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. Retifanlimab was granted Orphan Drug designation for the treatment of anal cancer, and this application was granted Fast Track designation and Priority Review.
