Incyte’s Zynyz Wins FDA Approval as Single and Combo Therapy for Anal Cancer

The FDA has approved Zynyz (retifanlimab-dlwr) for the treatment of adults with squamous cell carcinoma of the anal canal (SCAC).

The approval includes its use in combination with carboplatin and paclitaxel for first-line treatment of inoperable locally recurrent or metastatic SCAC, as well as monotherapy for patients with disease progression on or intolerance to platinum-based chemotherapy.

This is the second approval for Zynyz, which got its first FDA nod in 2023 for the treatment of metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).

The current win in SCAC comes four years after the FDA first rejected it in the indication.

SCAC is the most common form of anal cancer, accounting for around 85% of cases. Although considered rare, its incidence is rising by about 3% annually.

Nearly 90% of cases are linked to human papillomavirus (HPV) infection, the leading risk factor for anal cancer. Additionally, HIV significantly increases risk, with individuals living with HIV being 25 to 35 times more likely to develop the disease.

SCAC often shares symptoms with benign conditions like hemorrhoids — such as pain, itching, a lump or mass and changes in bowel habits — making early detection difficult. As a result, many patients are diagnosed with locally advanced disease.

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Zynyz is a monoclonal antibody targeting programmed death receptor-1 (PD-1).

“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,” said Incyte’s CEO Hervé Hoppenot in a statement announcing the approval.

“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 US patients with SCAC.”

The approval was based on results from two trials. The Phase III POD1UM-303 trial enrolled 308 chemotherapy-naïve patients with inoperable locally recurrent or metastatic SCAC. Patients received carboplatin and paclitaxel and were randomized to receive either retifanlimab-dlwr or placebo. The primary endpoint was progression-free survival (PFS).

Zynyz cut the risk of disease progression or death by 37% compared to chemotherapy alone.

Results demonstrated a median PFS of 9.3 months in the Zynyz arm compared to 7.4 months in the placebo arm.

The overall response rate (ORR) was 56% in the Zynyz group versus 44% in the placebo group.

Interim overall survival data showed a median of 29.2 months for Zynyz and 23 months for placebo, although this difference was not statistically significant. Further follow-up on overall survival is ongoing.

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Zynyz’s approval as a monotherapy in the indication was based on results from the POD1UM-202 study, which demonstrated that treatment with Zynyz monotherapy produced an ORR of 14% and a disease control rate of 49% among 94 patients.

Phase II POD1UM-202 trial evaluated Zynyz monotherapy in 94 patients with SCAC who had disease progression on or intolerance to platinum-based chemotherapy. The ORR was 14%, with a median duration of response of 9.5 months.

Hoppenot has previously said that the company does not anticipate Zynyz to be a major revenue driver. He previously described the drug as an “opportunistic product” aimed at expanding first-line access to PD-1 therapies in regions outside of the core US and European markets.

In the first quarter of 2025, Zynyz generated $3 million in sales, a small portion of Incyte’s approximately $1 billion in total revenue for the quarter.

Zynyz received Orphan Drug designation for the treatment of anal cancer, and Fast Track designation and Priority Review were granted for the application in SCAC.