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

On May 15, 2025, the U.S. Food and Drug Administration (FDA) approved Zynyz® (retifanlimab-dlwr), developed by Incyte, as the first and only approved first-line treatment for adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). This approval encompasses both combination therapy with chemotherapy and monotherapy .(Business Wire, AJMC)

About Zynyz (Retifanlimab-dlwr)

Zynyz is a humanized monoclonal antibody that targets programmed death receptor-1 (PD-1), a protein that plays a role in downregulating the immune system. By inhibiting PD-1, Zynyz enhances the body's immune response against cancer cells .(Business Wire)

Clinical Trial Evidence

The FDA's approval was based on data from two pivotal clinical trials:(Business Wire)

• POD1UM-303/InterAACT2 (Phase 3): This randomized, double-blind trial evaluated the efficacy of retifanlimab-dlwr in combination with carboplatin and paclitaxel in 308 chemotherapy-naïve patients with inoperable locally recurrent or metastatic SCAC. The combination therapy demonstrated a median progression-free survival (PFS) of 9.3 months compared to 7.4 months in the placebo group, representing a 37% reduction in the risk of disease progression or death (hazard ratio [HR] 0.63; p=0.0006). The overall response rate (ORR) was 56% in the treatment arm versus 44% in the control arm .(U.S. Food and Drug Administration, OncLive)

• POD1UM-202 (Phase 2): This open-label, single-arm trial assessed retifanlimab-dlwr as a monotherapy in 94 patients with locally recurrent or metastatic SCAC who had disease progression on or intolerance to platinum-based chemotherapy. The study reported a tumor shrinkage in 14% of patients and disease control in 49% .(U.S. Food and Drug Administration, Curetoday)

Safety Profile

In the combination therapy arm of the POD1UM-303/InterAACT2 trial, serious adverse reactions occurred in 47% of patients, with sepsis and pulmonary embolism being the most frequent. Other common side effects included anemia, nausea, and alopecia. No new safety signals were identified, and the safety profile was consistent with other PD-1 inhibitors .(AJMC, Pharmacy Times, Curetoday)

Significance of the Approval

This FDA approval marks a significant advancement in the treatment landscape for advanced anal cancer, a condition that has historically had limited therapeutic options. Zynyz offers both a new first-line treatment in combination with chemotherapy and a monotherapy option for patients who have progressed on or are intolerant to platinum-based chemotherapy .(Business Wire)

For more detailed information, you can refer to the FDA's official announcement: (U.S. Food and Drug Administration).