Retifanlimab-dlwr with carboplatin and paclitaxel is approved by the USFDA and as a single agent for squamous cell carcinoma of the anal canal

On May 15, 2025, the Food and Drug Administration sanctioned retifanlimab-dlwr (Zynyz, Incyte Corporation) in conjunction with carboplatin and paclitaxel for the initial treatment of people with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The FDA has approved retifanlimab-dlwr as a monotherapy for people with locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) who have experienced disease progression or intolerance to platinum-based chemotherapy.

The efficacy of retifanlimab-dlwr in conjunction with carboplatin and paclitaxel was assessed in POD1UM-303/InterAACT 2 (NCT04472429), a randomized, multicenter, double-blind trial involving 308 patients with chemotherapy-naïve inoperable locally recurrent or metastatic squamous cell anal carcinoma (SCAC). Patients were administered carboplatin at an AUC of 5 on Day 1, and paclitaxel at a dosage of 80 mg/m² on Days 1, 8, and 15 for a total of 6 cycles, and were thereafter randomized (1:1) to receive either:

Retifanlimab-dlwr 500 mg administered intravenously every four weeks, or placebo administered intravenously every four weeks.
The primary effectiveness endpoint was progression-free survival (PFS), evaluated by blinded independent central review (BICR) in accordance with RECIST v1.1. Overall survival (OS) constituted a key secondary goal. The supplementary efficacy outcome measures included overall response rate (ORR) and duration of response (DOR), evaluated by BICR.

The median progression-free survival (PFS) was 9.3 months (95% confidence interval: 7.5, 11.3) in the retifanlimab-dlwr group and 7.4 months (95% confidence interval: 7.1, 7.7) in the placebo group, with a hazard ratio of 0.63 (95% confidence interval: 0.47, 0.84) and a p-value of 0.0006. The interim overall survival (OS) data were not statistically significant: the median OS was 29.2 months (95% confidence interval [CI]: 24.2, not estimable [NE]) and 23 months (95% CI: 15.1, 27.9) in the respective groups (hazard ratio 0.70 [95% CI: 0.49, 1.01]). Forty-five percent of patients administered a placebo subsequently received retifanlimab-dlwr following disease progression. The overall response rate (ORR) was 56% (95% CI: 48, 64) in one arm and 44% (95% CI: 36, 52) in the other arm.

The effectiveness of retifanlimab-dlwr as a monotherapy was assessed in POD1UM-202 (NCT03597295), an open-label, multicenter, single-arm study involving 94 patients with locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) who experienced disease progression or intolerance to platinum-based chemotherapy. Patients were administered retifanlimab-dlwr 500 mg intravenously every four weeks until disease progression, intolerable toxicity, or a maximum of 24 months.

The primary efficacy endpoints were overall response rate (ORR) and duration of response (DOR), evaluated by an independent review committee (IRC) in accordance with RECIST v1.1. The overall response rate (ORR) was 14% (95% confidence interval: 8, 23), and the median duration of response (DOR) was 9.5 months (95% confidence interval: 4.4, not estimable [NE]).

The prescribing information for retifanlimab-dlwr contains warnings and precautions for severe and deadly immune-mediated adverse responses, infusion-related reactions, problems of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

The advised dosage of retifanlimab-dlwr in conjunction with carboplatin and paclitaxel is 500 mg every four weeks until disease progression, intolerable toxicity, or a maximum of 12 months. The advised dosage of retifanlimab-dlwr as a monotherapy is 500 mg every four weeks until disease progression, intolerable toxicity, or a maximum of 24 months. Consult the medical information for carboplatin and paclitaxel for recommended dose guidelines in conjunction with retifanlimab.