European Commission Approves Zynyz® (retifanlimab) as a First-Line Treatment for Patients with Advanced Squamous Cell Carcinoma of the Anal Canal (SCAC)
Incyte has announced that the European Commission has granted approval for Zynyz (retifanlimab) to be used in combination with platinum-based chemotherapy as a first-line treatment for adults diagnosed with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal. The decision represents a significant regulatory milestone for the company and introduces a new therapeutic option for patients facing a rare and historically difficult-to-treat cancer.
Under the approval, Zynyz can be administered alongside the chemotherapy agents Carboplatin and Paclitaxel. This combination therapy is intended for patients whose disease has spread to other parts of the body or has returned locally but cannot be surgically removed. The approval marks an important step in advancing treatment strategies for squamous cell carcinoma of the anal canal (SCAC), a malignancy that has seen limited therapeutic innovation over the past several decades.
Addressing an Unmet Need in a Rare Cancer
SCAC is a relatively uncommon form of cancer that develops in the tissues of the anal canal. Because of its rarity, treatment options have historically been limited, and advances in therapy have been slow compared with more common cancers. For patients with advanced or metastatic disease, the prognosis has traditionally been poor, with few effective first-line treatments available.
According to Bill Meury, President and Chief Executive Officer of Incyte, the approval of Zynyz in the European Union represents a meaningful advancement for patients and clinicians alike.
He noted that the decision by European regulators marks an important step forward for individuals living with advanced SCAC, emphasizing that the disease has seen little progress in treatment innovation for many years. The availability of Zynyz in combination with platinum-based chemotherapy expands the treatment landscape and offers clinicians a new standard-of-care option.
Meury also highlighted that the therapy is the first programmed death-1 (PD-1) immunotherapy approved in Europe for use in combination with platinum-based chemotherapy in the first-line setting for this disease. The approval underscores Incyte’s broader commitment to developing innovative medicines designed to improve outcomes for patients with difficult-to-treat cancers.
Regulatory Pathway and Previous Approval
The European Commission’s decision follows a positive recommendation issued in January 2026 by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). Positive CHMP opinions are a key step in the European regulatory process and typically precede final authorization by the European Commission.
With this decision, Zynyz now has two approved indications in Europe. Prior to the new authorization in SCAC, the therapy had already received approval from the European Commission as a monotherapy for adults with metastatic or recurrent locally advanced Merkel cell carcinoma. Merkel cell carcinoma is another rare but aggressive skin cancer, and the earlier approval marked Zynyz’s first indication in the European market.
Clinical Trial Evidence Supporting Approval
The regulatory approval for Zynyz in SCAC is supported by results from the Phase 3 POD1UM-303/InterAACT2 clinical trial. This randomized study evaluated the safety and efficacy of Zynyz compared with placebo when both were administered alongside platinum-based chemotherapy consisting of carboplatin and paclitaxel.
The trial enrolled adult patients with metastatic or inoperable locally recurrent SCAC who had not previously received systemic chemotherapy for advanced disease. Participants were assigned to receive either the immunotherapy combination or chemotherapy with a placebo.
Findings from the study demonstrated a statistically significant improvement in clinical outcomes for patients receiving Zynyz. The trial showed a 37 percent reduction in the risk of disease progression or death compared with chemotherapy alone, representing a meaningful improvement in treatment effectiveness.
Progression-free survival (PFS), a key measure of how long patients live without their disease worsening, was also improved in the Zynyz treatment group. Patients receiving the immunotherapy and chemotherapy combination experienced a median PFS of 9.3 months, compared with 7.4 months for those receiving chemotherapy with placebo.
These results were considered statistically significant, with a p-value of 0.0006, indicating a strong likelihood that the observed benefit was attributable to the therapy rather than chance. The trial results were also published in the respected medical journal The Lancet, further highlighting the importance of the findings within the oncology community.
Improvements Across Secondary Endpoints
Beyond the primary endpoint of progression-free survival, the study also demonstrated improvements across multiple secondary measures of efficacy. Among the most important was overall survival, which reflects the length of time patients remain alive after beginning treatment.
Patients receiving Zynyz alongside chemotherapy showed clinically meaningful improvements in these secondary outcomes compared with those receiving chemotherapy alone. These findings suggest that the therapy may offer broader benefits in disease management and patient outcomes beyond delaying disease progression.
Safety Profile and Adverse Events
The safety profile of Zynyz observed in the POD1UM-303/InterAACT2 study was consistent with previously reported experiences involving PD-1 inhibitor therapies used in combination with chemotherapy. Researchers did not identify any new or unexpected safety concerns during the trial.
However, as with many cancer therapies, treatment was associated with certain adverse reactions. Serious adverse events were reported in approximately 47 percent of patients receiving the Zynyz and chemotherapy combination.
Among the most commonly reported serious adverse reactions—occurring in at least two percent of patients—were sepsis, pulmonary embolism, diarrhea, and vomiting. These findings underscore the importance of careful monitoring by healthcare professionals when administering combination cancer therapies.
Expanding the Role of Immunotherapy in SCAC
The approval of Zynyz reflects the growing role of immunotherapy in oncology, particularly therapies that target immune checkpoints such as the PD-1 pathway. By blocking the PD-1 protein, these treatments help restore the immune system’s ability to recognize and attack cancer cells.
With the addition of Zynyz to first-line treatment regimens for advanced SCAC in Europe, clinicians now have a new option that combines the immune-activating effects of PD-1 blockade with the established benefits of chemotherapy.
For patients facing metastatic or recurrent disease, this combination approach may offer improved disease control and potentially longer survival. The approval also reinforces ongoing efforts within the pharmaceutical industry to develop targeted therapies and immunotherapies for rare cancers that have historically received limited research attention.
As Incyte continues to expand the clinical development program for Zynyz, the therapy may play an increasingly important role in the treatment of several challenging malignancies, providing new hope for patients and healthcare providers seeking more effective treatment strategies.
About Squamous Cell Carcinoma of the Anal Canal (SCAC)
Worldwide, SCAC is the most common type of anal cancer, making up 85% of cases.2 It is a rare disease for which the incidence increases approximately 3% per year, with an estimated prevalence at around 1 or 2 cases per 100,000 people.3,4,5,6 About 90% of cases are associated with human papillomavirus (HPV) infection—the number one risk factor for anal cancer.5
HIV is an important amplifier of anal cancer, as people with HIV are 25 to 35 times more likely to develop it.7,8 Anal cancer shares many of the same symptoms as non-cancerous conditions, such as hemorrhoids—including pain, itching, a lump or mass and changes in bowel movements—and as a result can go undetected leading to the majority of patients presenting with locally advanced disease.9
About POD1UM
The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-303, POD1UM-202 and several other Phase 1, 2 and 3 studies for patients with solid tumors. For more information about the study, please visit https://clinicaltrials.gov/study/NCT04472429.
About Zynyz® (retifanlimab)
Zynyz® (retifanlimab) is a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), indicated in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) in the U.S and Japan and as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression or intolerance to platinum-based chemotherapy in the U.S.
Zynyz is also indicated as monotherapy for the first-line treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) in the U.S., EU, Canada and Switzerland.
Zynyz is marketed by Incyte in the U.S. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab.
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