FDA Issues CRL for Retifanlimab/Chemotherapy in Metastatic NSCLC

The FDA issued a complete response letter (CRL) for a supplemental biologics license application (sBLA) seeking approval for retifanlimab-dlwr (Zynyz) plus platinum-containing chemotherapy for adults with metastatic non–small cell lung cancer (NSCLC), according to a document from the United States Securities and Exchange Commission.¹

In the CRL, the agency identified inspection findings related to Catalent Indiana, LLC, a third-party fill-finish facility mentioned in the sBLA for the retifanlimab regimen. According to the agency, the third-party facility showed regulatory compliance issues, which were the sole factor impacting the approvability of the treatment combination. The CRL did not describe other concerns related to approvability, including any efficacy and safety data for retifanlimab or the third-party drug substance manufacturer.

The developers of retifanlimab, Incyte Corporation, aim to work closely with the FDA and Catalent Indiana to mitigate the issues highlighted in the CRL, which may support resubmission of the sBLA for retifanlimab in this NSCLC population.

Supporting clinical data for the sBLA originally came from the phase 3 POD1UM-304 trial (NCT04205812) evaluating platinum-based chemotherapy with or without retifanlimab among patients with NSCLC. Investigators previously presented findings from the POD1UM-304 trial at the European Society for Medical Oncology (ESMO) Asia Congress 2024 in December 2024.²

Data showed a median overall survival (OS) of 18.1 months with retifanlimab plus chemotherapy vs 13.4 months with placebo plus chemotherapy (HR, 0.75; 95% CI, 0.60-0.93; P = .0042). Additionally, the median progression-free survival (PFS) was 7.7 months and 5.5 months in each respective arm (HR, 0.64; 95% CI, 0.52-0.79; P <.0001). With each respective regimen, the objective response rate (ORR) was 52% (95% CI, 47%-57%) vs 39% (95% CI, 32%-46%; P = .0012), and the median duration of response (DOR) was 12.7 months (95% CI, 9.4-15.2) vs 6.1 months (95% CI, 4.2-8.3).

Treatment with retifanlimab in the POD1UM-304 trial was well-tolerated, and data revealed no new safety issues. Common treatment-emergent adverse effects (TEAEs) included anemia (62.7%), decreased appetite (22.6%), and decreased neutrophil counts (22.1%) in the retifanlimab arm.

“Lung cancer is the leading cause of cancer deaths globally, with the high majority of cases being NSCLC. I am encouraged by the observed safety and efficacy profile of retifanlimab when added to platinum-based chemotherapy in this patient population and believe the positive results from the POD1UM-304 trial support retifanlimab in combination with chemotherapy as an additional treatment option for previously untreated metastatic NSCLC,” Shun Lu, MD, PhD, from Shanghai Chest Hospital, stated in a press release on these data.²

Investigators of the international, multicenter, double-blind phase 3 POD1UM-304 trial assessed platinum-based chemotherapy plus retifanlimab or matched placebo among those with frontline, metastatic squamous or nonsquamous NSCLC. Patients were assigned to receive retifanlimab or placebo intravenously every 3 weeks on day 1 of each cycle for a maximum of 35 cycles in combination with chemotherapy.³

The trial’s primary end point was OS. Secondary end points included PFS, ORR, DOR, and TEAEs. Patients 18 years and older with histologically confirmed squamous or nonsquamous stage IV NSCLC, no prior systemic therapy for NSCLC, measurable disease per RECIST v1.1 guidelines, and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial.

Developers designed retifanlimab as an intravenously administered PD-1 inhibitor. In May 2025, the FDA approved frontline retifanlimab plus platinum-based chemotherapy for adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal.⁴

References

1. United States Securities and Exchange Commission. Form 8-K. Incyte Corporation. Published February 27, 2026. Accessed March 10, 2026. https://tinyurl.com/yc2emb96
2. Incyte announces positive results from phase 3 trial evaluating retifanlimab (Zynyz®) in combination with platinum-based chemotherapy in patients with non-small cell lung cancer. News release. Incyte Corporation. December 7, 2024. Accessed March 10, 2026. https://tinyurl.com/4mea6kvu
3. Platinum-based chemotherapy with/​without INCMGA00012, an anti-PD-1 antibody, in non-small cell lung cancer (POD1UM-304). ClinicalTrials.gov. Updated March 10, 2026. Accessed March 10, 2026. https://tinyurl.com/hxwyb9xu
4. 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 Corporation. May 15, 2025. Accessed March 10, 2026. https://tinyurl.com/48aaubht