FDA Approves Zynyz Treatment Regimen for Advanced Anal Cancer

The United States Food and Drug Administration (FDA) has approved first-line treatment with Zynyz (retifanlimab-dlwr) in combination with the platinum-based carboplatin and paclitaxel chemotherapy for adult patients with inoperable, locally recurrent or metastatic squamous cell carcinoma of the anal canal, according to a news release from Incyte.

Furthermore, the FDA also granted approval for Zynyz as a single agent for adult patients with locally recurrent or metastatic squamous cell carcinoma of the anal canal following disease progression on or intolerance to platinum-based chemotherapy.

"The FDA approval of Zynyz marks a pivotal moment, bringing effective combination and monotherapy treatment options to patients with advanced anal cancer after decades of limited innovation," Hervé Hoppenot, CEO of Incyte, said in the news release. "At Incyte, we focus our efforts where we can make the biggest impact for patients. I am proud of our scientists and development teams for their perseverance in delivering the first approved PD-1 inhibitor to U.S. patients with [squamous cell carcinoma of the anal canal].”

The FDA granted priority review to and approved Zynyz based on data from two trials: the POD1UM-303/InterAACT2 phase 3 study and the POD1UM-202 trial phase 2 study. The former trial investigated Zynyz plus chemotherapy in untreated advanced squamous cell carcinoma of the anal canal and the latter evaluated those with previously treated squamous cell carcinoma of the anal canal

Results from POD1UM-303/InterAACT2 showed a clinically meaningful 37% reduction in the risk of progression or death with the combination of Zynyz and chemotherapy. Patients receiving the combination had a median progression-free survival of 9.3 months compared with 7.4 months for those in the placebo group. An interim analysis also showed a 6.2-month improvement in median overall survival, with follow-up ongoing.

No new safety signals were reported. Serious side effects occurred in 47% of patients receiving Zynyz with chemotherapy; the most frequent were sepsis (3.2%), pulmonary embolism (3.2%), diarrhea (2.6%) and vomiting (2.6%).

"Patients with inoperable locally recurrent or metastatic anal cancer have historically faced poor five-year survival rates and limited treatment options. The POD1UM data highlight the potential of Zynyz to be a meaningful new option and notably demonstrate that the addition of Zynyz to platinum-based chemotherapy significantly improves progression-free survival," Dr. Marwan Fakih, said in the news release. "This approval marks an important advancement as it makes a new treatment approach available for this challenging cancer."

Fakih is a professor of medical oncology and therapeutics research, associate director of clinical sciences, medical director of the Briskin Center for Clinical Research, division chief of gastrointestinal medical oncology, and co-director of the gastrointestinal cancer program at City of Hope.

Results were presented at the 2024 European Society for Medical Oncology (ESMO) Presidential Symposium on Practice-Changing Trials.

The FDA approved Zynyz as a single agent based on results from the POD1UM-202 study, which showed that 14% of patients experienced tumor shrinkage and 49% had disease control. The safety profile was consistent with other PD-1 inhibitors and did not affect HIV infection control. Serious side effects occurred in 40% of patients, with the most common including infections, pain, anemia, bleeding, diarrhea, fever and trouble breathing.

“Patients with anal cancer often face a troubling lack of public awareness and understanding when it comes to risk factors, symptoms and their overall cancer journey,” David Winterflood, chief executive officer of the Anal Cancer Foundation, said in the news release. “The approval of Zynyz marks a step forward for advanced [squamous cell carcinoma of the anal canal] treatment, brings attention to a long-overlooked condition with limited treatment options and offers patients whose anal cancer has returned or spread an option to treat their disease.”

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