The European Commission has approved Incyte’s Zynyz (retifanlimab) with carboplatin and paclitaxel as a first-line treatment for metastatic or inoperable locally recurrent anal cancer (SCAC), based on Phase 3 POD1UM-303 trial results showing improved progression-free survival.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
The European Commission has approved Zynyz (retifanlimab) in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal (SCAC). The decision marks an important milestone for patients with this rare malignancy, where treatment options have remained largely unchanged for decades.
Commenting on the approval, Bill Meury, President and Chief Executive Officer of Incyte, said the decision represents an important advance for patients with advanced SCAC, noting that meaningful therapeutic progress in this disease has been limited for many years. He added that as the first PD-1 immunotherapy approved in Europe in combination with platinum-based chemotherapy in the first-line setting, Zynyz expands treatment options for clinicians and reflects the company’s commitment to developing innovative therapies for patients.
Zynyz is a humanized monoclonal antibody targeting the PD-1 immune checkpoint pathway, helping restore immune responses against tumor cells. The therapy is developed and marketed by Incyte.
The approval follows a positive opinion issued in January 2026 by the European Medicines Agency’s Committee for Medicinal Products for Human Use. It represents the second approved indication for Zynyz in the European Union, where it had previously been authorized as monotherapy for adults with metastatic or recurrent locally advanced Merkel cell carcinoma.
The regulatory decision was supported by results from the Phase 3 POD1UM-303/InterAACT2 trial (NCT04472429), which evaluated retifanlimab or placebo in combination with carboplatin and paclitaxel in patients with metastatic or inoperable locally recurrent SCAC who had not received prior systemic chemotherapy. Findings from the trial, published in The Lancet, showed that the addition of Zynyz significantly improved outcomes compared with chemotherapy alone.
Patients receiving the Zynyz-chemotherapy combination experienced a 37% reduction in the risk of disease progression or death. Median progression-free survival reached 9.3 months in the Zynyz arm compared with 7.4 months in the placebo combination group. Improvements were also observed across secondary endpoints, including overall survival, indicating a meaningful clinical benefit in this patient population.
The safety profile of the combination therapy was consistent with other PD-1 inhibitor and chemotherapy regimens. Serious adverse reactions occurred in about 47% of patients treated with Zynyz plus chemotherapy. The most frequently reported serious events included sepsis, pulmonary embolism, diarrhea and vomiting. No new safety signals were identified during the study.
Squamous cell carcinoma of the anal canal accounts for approximately 85% of all anal cancer cases worldwide. Although rare, its incidence has been increasing by roughly 3% per year, with an estimated prevalence of one to two cases per 100,000 people. Around 90% of cases are associated with infection by the human papillomavirus (HPV), the primary risk factor for the disease, while individuals living with HIV face a substantially higher risk, estimated to be 25 to 35 times greater than the general population.
Because symptoms often resemble benign conditions such as hemorrhoids, including pain, itching, or changes in bowel habits, many patients are diagnosed only after the disease has progressed to an advanced stage.
Retifanlimab is being investigated across multiple tumor types under the broader POD1UM clinical program, which includes several Phase 1, 2 and 3 studies evaluating the PD-1 inhibitor in patients with solid tumors. With this latest approval, Zynyz expands first-line treatment options for patients with advanced SCAC in Europe and reinforces the growing role of immunotherapy-chemotherapy combinations in rare cancers.
Reference
Incyte Announces the European Commission Approval of Zynyz® (retifanlimab) for the First-Line Treatment of Advanced Squamous Cell Carcinoma of the Anal Canal (SCAC), 06 March 2026, Incyte Announces the European Commission Approval of Zynyz® (retifanlimab) for the First-Line Treatment of Advanced Squamous Cell Carcinoma of the Anal Canal (SCAC) | Incyte
Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2), ClinicalTrials.gov ID NCT04472429, https://clinicaltrials.gov/study/NCT04472429
Rao S et al, POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin-paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. Front Oncol. 2022 Aug 24;12:935383, PMID: 36091159; PMCID: PMC9449327, https://doi.org/10.3389/fonc.2022.935383
About Writer
Chikkula Pavan Kumar, Pharm.D.
He is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.