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FDA Approves Retifanlimab for Advanced Anal Cancer

The FDA approved frontline retifanlimab/chemotherapy for metastatic SCAC and retifanlimab monotherapy for metastatic SCAC with progression on chemotherapy.

US FDA

US FDA

The FDA has approved retifanlimab-dlwr (Zynyz) in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).1 The FDA has also approved retifanlimab as 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 based on findings from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429) investigating retifanlimab plus platinum-based chemotherapy (carboplatin plus paclitaxel) in adult patients with metastatic or inoperable locally recurrent SCAC who were not previously treated with systemic chemotherapy, as well as from the phase 2 POD1UM-202 trial (NCT03597295) evaluating retifanlimab monotherapy in previously treated patients with locally advanced or metastatic SCAC who had progressed on or were intolerant to platinum-based chemotherapy.

Data from the POD1UM-303 study, which were presented at the 2024 ESMO Congress, demonstrated a clinically meaningful and statistically significant reduction in the risk of progression or death with retifanlimab plus chemotherapy vs placebo plus chemotherapy.1,2 Patients treated with retifanlimab plus chemotherapy had a median progression-free survival (PFS) of 9.3 months (95% CI, 7.5-11.3) vs 7.4 months (95% CI, 7.1-7.7) for those who received placebo plus chemotherapy (HR, 0.63; 95% CI, 0.47-0.84; P=.0006). Furthermore, the median overall survival (OS) was 29.2 months (95% CI, 24.2-not evaluable) vs 23 months (95% CI, 15.1-27.9) in these respective arms (HR, 0.70; 95% CI, 0.49-1.01; P=00273).2 Follow-up for OS is ongoing.1

"Patients with inoperable locally recurrent or metastatic anal cancer have historically faced poor 5-year survival rates and limited treatment options," Marwan Fakih, MD, a 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 in Duarte, California, stated in a news release. "The [POD1UM-303] 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. This approval marks an important advancement as it makes a new treatment approach available for this challenging cancer."

Additionally, in POD1UM-303, retifanlimab elicited an overall response rate (ORR) of 56% (95% CI, 48%-64%), including complete response and partial response rates of 22% and 34%, respectively.2 The median duration of response was 14.0 months (95% CI, 8.6-22.2).

Investigators observed no new safety signals with retifanlimab in this trial.1 Serious adverse effects (AEs) were reported in 47% of patients receiving retifanlimab plus chemotherapy. The most frequent serious AEs in the retifanlimab arm (occurring in ≥ 2% of patients) were sepsis (3.2%), pulmonary embolism (3.2%), diarrhea (2.6%) and vomiting (2.6%).

“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, added in the news release. “The approval of retifanlimab marks a step forward for advanced SCAC 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.”

In the POD1UM-202 trial, patients who received retifanlimab monotherapy achieved an ORR of 14% (95% CI, 8%-23%) and a disease control rate of 49%.1,2 Retifanlimab had a safety profile consistent with that expected from a PD-1 inhibitor and was not associated with loss of HIV infection control.1 Serious AEs were reported in 40% of patients treated with retifanlimab. The most frequent serious AEs (observed in ≥ 2% of patients) were non-urinary tract infection, perineal pain, abdominal pain, anemia, hemorrhage, diarrhea, pyrexia, urinary tract infection, musculoskeletal pain, and dyspnea.

"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, concluded 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 United States patients with SCAC.”

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://investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-zynyzr-retifanlimab-dlwr-making-it
  2. Zynyz. Prescribing information. Incyte. May 2025. Accessed May 15, 2025. https://www.zynyz.com/zynyz-prescribing-information

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