European Commission OKs Retifanlimab Combo in Metastatic Anal Canal Cancer

The European Commission (EC) approved retifanlimab-dlwr (Zynyz) in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with metastatic or locally recurrent squamous cell carcinoma of the anal canal (SCAC), according to a press release from the developer, Incyte.¹

This decision follows the European Medicines Agency’s Committee for Medicinal Products for Human Use’s adoption of a positive opinion for this treatment regimen in January 2026.²

The approval is based on findings from the global, phase 3 POD1UM-303/InterAACT-2 trial (NCT04472429), which evaluated the efficacy and safety of adding the PD-1 inhibitor to standard platinum-based chemotherapy.³

“The EC approval of [retifanlimab] marks an important step forward for patients with advanced SCAC, a rare cancer for which meaningful treatment advances have not occurred in several decades,” stated Bill Meury, president and chief executive officer of Incyte, in the press release.¹ “As the first PD-1 immunotherapy approved in Europe in combination with platinum-based chemotherapy in the first-line setting, [retifanlimab] helps expand the standard-of-care options available to clinicians and underscores our commitment to delivering innovative medicines that can have an impact for patients.”

Clinical Efficacy and Survival Outcomes

Results from the POD1UM-303 trial demonstrated that retifanlimab plus chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared with placebo plus chemotherapy. According to investigator-assessed data, the median PFS was 9.3 months (95% CI, 7.5-11.3) in the retifanlimab arm vs 7.4 months (95% CI, 7.1-7.7) in the placebo arm. This improvement represented a 37% reduction in the risk of disease progression or death (HR, 0.63; 95% CI, 0.47-0.84; P = .0006).

The combination also yielded a significant benefit in OS, with a median OS of 29.2 months (95% CI, 24.2–not evaluable) for patients receiving retifanlimab compared with 23.0 months (95% CI, 15.1-27.9) for those in the control group. The investigators noted that there was evidence of improved survival despite survival data being immature (HR, 0.70; 95% CI, 0.49-1.01; P = .027). Furthermore, the objective response rate (ORR) was 55.8% (95% CI, 47.6%-63.8%) in the retifanlimab arm compared with 44.2% (95% CI, 36.2%-52.4%) in the placebo arm. The median duration of response was also extended, reaching 14.0 months (95% CI, 8.6-22.2) for the retifanlimab combination vs 7.2 months (95% CI, 5.6-9.3) for the placebo combination.

Trial Breakdown and Patient Population

The phase 3 POD1UM-303 trial randomly assigned 308 patients with locally recurrent or metastatic SCAC in a 1:1 ratio. The experimental regimen consisted of 500 mg of retifanlimab administered as a 30-minute intravenous infusion before scheduled carboplatin/paclitaxel on day 1 of a 28-day cycle, while the control group received a matching placebo. Both arms received chemotherapy consisting of carboplatin at area under the curve 5 mg/mL on day 1 and paclitaxel at 80 mg/m² on days 1, 8, and 15 of a 28-day cycle for up to 6 cycles.

Eligible patients were required to be chemotherapy naive for metastatic or locally recurrent disease. Patients who had received prior definitive chemoradiotherapy were eligible if the treatment was completed at least 6 months prior to enrollment. All patients had an ECOG performance status of 0 or 1. Sorting was stratified by geographic region, extent of disease, and PD-L1 expression.

Safety and Tolerability

The safety profile of retifanlimab in combination with chemotherapy was generally consistent with the known profiles of the individual agents. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 83% of patients in the retifanlimab group and 75% of patients in the placebo group. Immune-related AEs occurred in 49% of patients in the retifanlimab group and 26% of the placebo group, most of which were grade 1 or 2.

References

1. Incyte announces European Commission approval of ZYNYZ (retifanlimab). News release. Incyte. Published March 6, 2026. Accessed March 9, 2026. https://tinyurl.com/3rsc2t6u
2. Incyte announces positive CHMP opinion for Zynyz® (retifanlimab) for first-line treatment of advanced squamous cell carcinoma of the anal canal (SCAC). News release. Incyte. January 30, 2026. Accessed March 6, 2026. https://tinyurl.com/tsjrsv2k
3. Rao S, Samalin-Scalzi E, Evesque L, et al. Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial. Lancet. 2025;405(10494):2144-2152. doi:10.1016/S0140-6736(25)00631-2