- Incyte's (INCY, Financial) retifanlimab (Zynyz®) shows significant effectiveness in treating advanced squamous cell carcinoma of the anal canal (SCAC).
- The Phase 3 trial demonstrated a 37% reduction in the risk of disease progression or death when combined with carboplatin and paclitaxel.
- FDA approved Zynyz® in May 2025 for first-line treatment in the U.S., with global regulatory submissions under review.
Incyte (INCY) has announced the publication of primary results from its Phase 3 POD1UM-303/InterAACT 2 trial in The Lancet, highlighting the efficacy of retifanlimab (Zynyz®) when used in combination with carboplatin and paclitaxel in patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). This marks the first and largest global Phase 3 trial assessing a PD-1 inhibitor in combination with chemotherapy for advanced SCAC.
The trial successfully met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS). Results indicated a reduction in the risk of disease progression or death by 37% (HR: 0.63; 95% CI: 0.47, 0.84; P=0.0006). Patients treated with the retifanlimab-chemotherapy combination achieved a median PFS of 9.3 months versus 7.4 months in the placebo group.
In May 2025, the U.S. Food and Drug Administration (FDA) approved Zynyz® for use as the first-line treatment in adult patients with advanced SCAC. Submissions to other global regulatory bodies are underway, with evaluations by European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in progress.
The combination treatment also showed a consistent benefit across all pre-defined subgroups and a clinically meaningful 6-month difference in overall survival (OS) at interim analysis, despite the OS results not reaching statistical significance. Retifanlimab in conjunction with chemotherapy also improved the overall response rate (ORR) to 55.8% compared to 44.2% with placebo, and extended the median duration of response to 14 months, double that of the placebo group.
Safety findings were consistent with expected results for chemotherapy combined with a PD-1 inhibitor, with manageable risks and no new safety concerns reported. Grade 3 or more severe adverse events were more frequent in the treatment group (47.4%) compared to the placebo group (38.8%).
