Dr Fakih on the FDA Approval of Retifanlimab for Advanced Anal Cancer

"This FDA approval [indicates] an immunotherapy drug for the first time, and [this is] an area where there is a significant unmet need.”

Marwan Fakih, MD, a professor in Department of Medical Oncology & Therapeutics Research, associate director for Clinical Sciences Medical, director of the Briskin Center for Clinical Research, division chief of GI Medical Oncology, and co-director of the Gastrointestinal Cancer Program at City of Hope, discussed the clinical relevance of the FDA’s approval of retifanlimab-dlwr (Zynyz) for patients with squamous cell carcinoma of the anal canal (SCAC).

On May 15, 2025, the FDA approved retifanlimab in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic SCAC; and as a monotherapy for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. These regulatory decisions were supported by efficacy and safety findings from the phase 3 POD1UM-303/InterAACT 2 (NCT04472429) and the phase 2 POD1UM-202 (NCT03597295) trials.

In the randomized, double-blind POD1UM-303 trial, patients who received retifanlimab plus chemotherapy experienced a statistically significant improvement in progression-free survival (PFS) compared with those who received placebo plus chemotherapy (HR, 0.63; 95% CI, 0.47–0.84; P = .0006). The median PFS was 9.3 months (95% CI, 7.5-11.3) in the investigational arm vs 7.4 months (95% CI, 7.1-7.7) in the control arm. Additionally, a trend toward improved overall survival (OS) was observed at a median of 29.2 months (95% CI, 24.2-not evaluable) vs 23.0 months (95% CI, 15.1–27.9), respectively (HR, 0.70; 95% CI, 0.49-1.01; P = .0273).

Fakih noted that this represents the first phase 3 evidence supporting an immunotherapy-based regimen in SCAC, replacing the historical reliance on chemotherapy alone—typically carboplatin and paclitaxel, which had been adopted from phase 2 data rather than from randomized, controlled trials.

The approval of retifanlimab monotherapy was informed by the POD1UM-202 trial, which enrolled patients with advanced SCAC who had progressed on or were intolerant to platinum-based regimens. This study reinforced the clinical activity of retifanlimab in the refractory setting, providing an additional option for patients with limited alternatives.

Fakih emphasized that the dual approvals address a longstanding unmet need in SCAC and provide oncologists with evidence-based immunotherapy strategies across both the frontline and relapsed settings.