FDA

Zynyz approved for advanced anal cancer

May 19, 2025

FDA approved Zynyz (retifanlimab-dlwr) 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 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.

Zynyz is also approved for the treatment of recurrent locally advanced or metastatic Merkel cell carcinoma.

Efficacy

Efficacy of retifanlimab-dlwr with carboplatin and paclitaxel was evaluated in the randomized, multicenter, double-blind POD1UM-303/InterAACT 2 trial (NCT04472429) involving 308 patients with chemotherapy-naive 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 IV q4wks, or
• placebo IV q4wks.

The major efficacy outcome measure was progression-free survival (PFS). Overall survival (OS) was a key secondary endpoint. Additional efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). 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 [HR], 0.63; 95% CI, 0.47-0.84; p-value, 0.0006). Interim OS results weren’t 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 (HR, 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 IV q4wks 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, NE).

Safety

When retifanlimab is used in combination with carboplatin and paclitaxel, the most common adverse reactions reported were fatigue, peripheral neuropathy, nausea, alopecia, diarrhea, musculoskeletal pain, constipation, hemorrhage, rash, vomiting, decreased appetite, pruritis, and abdominal pain.

When used as a single agent in SCAC patients, the most common adverse reactions reported with retifanlimab were fatigue, musculoskeletal pain, diarrhea, non-urinary tract infections, perineal pain, hemorrhage, urinary tract infection, rash, nausea, decreased appetite, constipation, abdominal pain, dyspnea, pyrexia, vomiting, cough, pruritus, hypothyroidism, headache, and decreased weight.

The prescribing information for includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.

Recommended dose

The recommended retifanlimab-dlwr dosage in combination with carboplatin and paclitaxel is 500 mg q4wks until disease progression, unacceptable toxicity, or up to 12 months. The recommended dosage of retifanlimab-dlwr as a single agent is 500 mg q4wk 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.

Sources:

FDA approves retifanlimab-dlwr with carboplatin and paclitaxel and a single agent for squamous cell carcinoma of the anal canal. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-retifanlimab-dlwr-carboplatin-and-paclitaxel-and-single-agent-squamous-cell-carcinoma

Incyte announces FDA approval of Zynyz® (retifanlimab-dlwr) making it the first and only approved first-line treatment for advanced anal cancer patients in the United States. [News release]. 2025. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-zynyzr-retifanlimab-dlwr-making-it

Zynyz (retifanlimab-dlwr) [package insert]. Incyte. https://www.incytepicentral.com/sites/g/files/hssmmz4016/files/2025-05/combined-SCAC-label-05.15.25.pdf Revised May 2025. Accessed May 16, 2025.