FDA OKs Retifanlimab Combo in Recurrent/Metastatic Anal Cancer

The FDA based its decision on findings from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429).

The FDA has approved retifanlimab-dlwr (Zynyz) plus platinum-based chemotherapy with carboplatin and paclitaxel as frontline treatment for adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC), according to a press release from the developer, Incyte.1 Additionally, the agency approved retifanlimab as monotherapy for adults with recurrent or metastatic SCAC who experienced progressive disease or intolerance associated with platinum-containing chemotherapy.

Supporting data for the combination therapy indication came from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429), which evaluated retifanlimab/chemotherapy in patients without prior systemic chemotherapy. Findings presented at the 2024 European Society for Medical Oncology (ESMO) Congress showed a median progression-free survival (PFS) of 9.3 months with retifanlimab/chemotherapy vs 7.4 months with placebo/chemotherapy, eliciting a 37% reduction in the risk of death (P = .0006).2 The experimental combination also improved the median overall survival (OS) by 6.2 months (P = .0273). Additional analysis for OS in this trial is ongoing.

Data from this study showed no new safety signals. Serious adverse effects (SAEs) affected 47% of those in the retifanlimab arm, with the most common toxicities including 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 [had] poor 5-year survival rates and limited treatment options. The POD1UM data highlight the potential of [retifanlimab] to be a meaningful new option, and notably demonstrate that the addition of [retifanlimab] to platinum-based chemotherapy significantly improves [PFS]," Marwan Fakih, MD, professor of Medical Oncology & Therapeutics Research, associate director of 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, stated in the press release.1 "This approval marks an important advancement as it makes a new treatment approach available for this challenging cancer."

Additionally, findings from the phase 2 POD1UM-202 study (NCT03597295) supported the approval of retifanlimab monotherapy in this population. Efficacy data showed an objective response rate (ORR) of 14% as well as a disease control rate (DCR) of 49% with retifanlimab.

SAEs occurred in 40% of patients treated with retifanlimab in the POD1UM-202 study. The most common toxicities included non-urinary tract infections, perineal pain, abdominal pain, and anemia.

"The FDA approval of [retifanlimab] marks a pivotal moment, bringing effective combination and monotherapy treatment options to patients with advanced anal cancer after decades of limited innovation," Hervé Hoppenot chief executive officer of Incyte, added.1

References

1. 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. May 15, 2025. Accessed May 15, 2025. https://tinyurl.com/48aaubht
2. Incyte’s retifanlimab (Zynyz®) extends progression-free survival in patients with squamous cell anal carcinoma (SCAC); data featured at ESMO 2024 Presidential Symposium. News release. Incyte. September 14, 2024. Accessed May 15, 2025. https://tinyurl.com/c65kbbtj