Zynyz reflimab combined with chemotherapy was approved by the FDA for advanced anal cancer, analysis of efficacy and safety

In May 2025, the American pharmaceutical company Incyte (Incyte) announced that it has developed anti-PD-1immunotherapyZynyz (generic name: Retifanlimab-dlwr) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with locally recurrent or metastatic, inoperable squamous cell carcinoma of the anal canal (SCAC). This new drug can be used in combination with carboplatin and paclitaxel for initial treatment, or as a single agent for patients who have failed or are intolerant to platinum-based chemotherapy.

Anal canal squamous cell carcinoma is the most common type of anal cancer, accounting for the majority of anal cancer cases (about 85%). The disease is highly related to the human papillomavirus (HPV), and about 90% of patients are infected with the HPV virus. Because the clinical manifestations of anal cancer are easily confused with benign diseases such as hemorrhoids, such as lumps, itching, pain, and changes in bowel habits, early diagnosis is difficult, and many patients are diagnosed at an advanced stage. The launch of Zynyz provides a new treatment option for such patients.

Zynyz is a humanized PD-1 monoclonal antibody that blocks the immune escape path of tumor cells by binding to the PD-1 receptor on the surface of T cells, allowing the body's immune system to recognize and attack cancer cells. The drug has been approved for the treatment of advanced Merkel cell carcinoma as early as 2023. The new indication makes Zynyz the first immunotherapy drug approved by SCAC for first-line treatment in the United States.

The clinical value of Zynyz is mainly based on two important studies: POD1UM-202 and POD1UM-303. POD1UM-202 is a phase 2 clinical trial and included 94Patients with locally advanced or metastatic SCAC, all of whom had disease progression after receiving platinum-based chemotherapy. During the study, patients received 500 mg of Zynyz intravenously every four weeks. The results showed that the objective response rate (ORR) of monotherapy was 14%, with one person having a complete response and 12 having a partial response; the disease control rate was 49%. The median duration of remission was 9.5 months, and more than 60% of patients had remission lasting more than half a year.

Another phase III clinical studyPOD1UM-303 further verified the efficacy of Zynyz combined with carboplatin and paclitaxel. The study included 308 treatment-naïve patients with locally advanced or metastatic SCAC. The results showed that compared with placebo combined with chemotherapy, Zynyz combination treatment could significantly reduce the risk of disease progression or death by 37% and extend the median progression-free survival to 9.3 months, compared with 7.4 months in the control group. In terms of overall survival, although the difference did not reach statistical significance, Zynyz combination treatment still prolonged survival by 6.2 months.

In terms of safety, Zynyz’s common side effects are similar to those of other immunotherapy drugs. The most common adverse reactions in monotherapy include fatigue, diarrhea, pruritus, nausea, muscle pain, hypothyroidism, etc. During combined treatment, patients may also experience symptoms such as neuropathy, hair loss, rash, and bleeding. Due to the long course of treatment, some patients may need to adjust the dose to control side effects.

Zynyzis administered by intravenous infusion. Each bottle contains 500mg of active ingredient and is administered once every four weeks. If used as combination therapy, it can be used for up to 12 months; as a single agent, it can be used for up to 24 months or adverse reactions occur. This approval marks an important progress in the first-line treatment of anal canal squamous cell carcinoma, and also opens up a new path for immunotherapy of advanced tumors.

Reference materials: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. News release. Incyte. March 15, 2025.