FDA Declines Retifanlimab for Non–Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) declined approval of retifanlimab-dlwr for patients with metastatic non-small cell lung cancer (NSCLC) in the United States because of manufacturing concerns at a third-party facility, according to a recent Securities and Exchange Commission filing from drugmaker Incyte.

The company had submitted a supplemental application seeking to expand the drug’s use to include patients with metastatic NSCLC in combination with platinum-based chemotherapy. However, the FDA issued a complete response letter citing regulatory compliance issues at a manufacturing plant involved in producing the therapy.

According to the filing, the FDA’s decision was not related to concerns about the drug’s effectiveness or safety in patients with cancer. Instead, the agency pointed to inspection findings at a fill-finish manufacturing site in Indiana operated by Catalent, which is now owned by Novo Nordisk.

The facility’s regulatory compliance was identified as the only issue preventing approval, the company reported. The FDA did not raise concerns about the clinical data supporting the application.

Clinical trial results showed survival benefit for patients

The supplemental application was supported by results from the global, multicenter, randomized, double-blind POD1UM-304 clinical trial, which evaluated retifanlimab combined with chemotherapy for patients with metastatic NSCLC.

In the study, patients were randomly assigned to receive either retifanlimab or a placebo in combination with pemetrexed and either carboplatin or cisplatin.

The trial met its primary endpoint of overall survival. Patients who received retifanlimab plus chemotherapy had a median overall survival of 18.1 months compared with 13.4 months for those who received placebo with chemotherapy.

The trial also met several secondary endpoints. Progression-free survival was longer among patients who received retifanlimab with chemotherapy compared with those who received placebo with chemotherapy.

Median progression-free survival was 7.7 months in the retifanlimab group compared with 5.5 months in the placebo group.

Additional secondary endpoints included overall response rate and duration of response, which were assessed through blinded independent central review. Results from the study were published in The Lancet Respiratory Medicine.

POD1UM-304 trial evaluated retifanlimab with chemotherapy

The POD1UM-304 study was designed as a global, multicenter, randomized, double-blind phase 3 clinical trial evaluating retifanlimab combined with chemotherapy for patients with metastatic NSCLC.

Participants in the study were randomly assigned to receive retifanlimab or placebo alongside pemetrexed and either carboplatin or cisplatin.

The trial assessed several outcomes, including overall survival as the primary endpoint. Secondary endpoints included progression-free survival, overall response rate and duration of response. These outcomes were evaluated through blinded independent central review.

Retifanlimab is a PD-1 inhibitor. The FDA previously granted accelerated approval to the therapy in 2023 for patients with advanced Merkel cell carcinoma. In 2025, the drug also received approval as a frontline treatment for metastatic squamous cell carcinoma of the anal canal.

According to the Securities and Exchange Commission filing, Incyte is working with the FDA and the manufacturer to address the regulatory concerns cited in the complete response letter. The company reported that these efforts are intended to support a potential resubmission of the supplemental application.

Side effects reported in the study

The most common treatment-related side effects observed among patients who received retifanlimab in the clinical trial occurred in less than 10% of patients in the experimental group.

These side effects included anemia, decreased appetite and decreased neutrophil count.

According to the study findings, adding retifanlimab to chemotherapy did not affect chemotherapy administration.

The FDA previously raised similar manufacturing concerns involving the same Indiana facility in 2025 when it issued a complete response letter for a drug application in follicular lymphoma. The earlier regulatory action also followed an FDA inspection of the manufacturing site, although the specific issues identified at the plant were not publicly disclosed by the FDA or the companies involved.

References

1. “FDA Cites Manufacturing Issues in Lung Cancer Drug Rejection.” News Release. Oncology News Central. March 10, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

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