The U.S. Food and Drug Administration (FDA) has approved Zynyz (retifanlimab-dlwr) for the effective treatment of advanced squamous cell carcinoma of the anal canal (SCAC). It is a humanized monoclonal antibody that acts against programmed death receptor-1 (PD-1). PD-1 is a protein that regulates the immune system’s response to cancer. This drug is manufactured by Incyte, a biopharmaceutical company.
The FDA has approved Zynyz for two indications. Firstly, it is approved in combination with platinum-based chemotherapy (carboplatin and paclitaxel) for the initial treatment of adults with inoperable, locally recurrent, or metastatic SCAC. Secondly, Zynyz is approved as a monotherapy for adults with locally recurrent or metastatic SCAC who have experienced disease progression or intolerance to platinum-based chemotherapy.
Hervé Hoppenot, CEO of Incyte, stated that this FDA approval is a breakthrough for patients with advanced anal cancer, who have had very limited treatment options for decades. He appreciated the development teams for their relentless pursuit that led to the approval of the first PD-1 inhibitor for patients with SCAC in the U.S.
SCAC is the most common form of anal cancer and affects approximately 85% of all anal cancer cases. Although anal cancer is relatively rare, its frequency increases by around 3% per year. About 90% of cases are associated with human papillomavirus (HPV), which is the greatest risk factor for anal cancer. Furthermore, patients with human immunodeficiency virus (HIV) are 25 to 35 times more likely to develop anal cancer. Since symptoms like pain, itching, or alteration in bowel habit of SCAC may mimic non-malignant conditions like hemorrhoids, the disease often goes undiagnosed until its advanced stage.
FDA considered this approval based on evidence obtained from two significant clinical trials. The Phase 2 POD1UM-202 trial evaluated Zynyz as monotherapy for patients whose disease had continued to advance or who could no longer continue with platinum-based chemotherapy. The trial results indicated that Zynyz monotherapy resulted in an objective response rate (ORR) of 14% and a disease control rate (DCR) of 49%. 40% of patients reported serious adverse reactions, which included infections, abdominal pain and perineal pain, anemia, bleeding, fever, urinary tract infections, and shortness of breath. Importantly, Zynyz did not interfere with HIV infection control in patients living with HIV.
The results of the Phase 3 POD1UM-303/InterAACT2 trial were presented during the Presidential Symposium at the 2024 European Society for Medical Oncology (ESMO) Meeting. The trial demonstrated that patients treated with Zynyz with chemotherapy experienced a 37% risk reduction of disease progression or death (P=0.0006), compared to patients receiving chemotherapy plus placebo. Median progression-free survival (PFS) was 9.3 months in the Zynyz group versus 7.4 months in the placebo group. An interim analysis also demonstrated 6.2 months for overall survival (OS) (P=0.0273); however, the final OS results are still being monitored for assessment. No new safety concerns were observed.
However, side effects were notable. Severe adverse events were seen in 47% of patients who received the combination therapy. The most common serious adverse reactions were reported in ≥2% of patients, such as sepsis in 3.2% of patients, pulmonary embolism in 3.2%, diarrhea in 2.6%, and vomiting in 2.6%.
Patients with metastatic or inoperable anal cancer have previously faced poor survival rates and few treatment options. The addition of Zynyz to chemotherapy offers a meaningful improvement in progression-free survival and represents a significant advancement in care, as indicated by Dr. Marwan Fakih, M.D., professor and expert in gastrointestinal cancers, City of Hope.
“This approval brings not only a new treatment option but also much-needed attention to a cancer type that has long been misunderstood and overlooked,” said by David Winterflood, CEO, Anal Cancer Foundation.
This approval of Zynyz offers new hope for adults with advanced SCAC, providing both combination and monotherapy options where few effective treatments previously existed.
Reference: Incyte. 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. Published May 15, 2025. Accessed May 20, 2025. 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
