The FDA has issued a complete response letter (CRL) for a supplemental biologics license application (sBLA) seeking the approval of retifanlimab-dlwr (Zynyz) injection in combination with platinum-containing chemotherapy for the treatment of adult patients with metastatic non–small cell lung cancer (NSCLC).1
According to the CRL, the FDA cited inspection findings not specific to retifanlimab at Catalent Indiana, LLC, part of Novo Nordisk, which was the third-party fill-finish facility referenced in the sBLA. In the CRL, the agency cited regulatory compliance of the facility as the sole approvability issue; there were no other approvability concerns, including efficacy and safety data for retifanlimab in NSCLC or the third-party drug substance manufacturer. Incyte, the developers of the agent, plan to work closely with the FDA and the Catalent Indiana facility to address the CRL and support a potential sBLA submission for retifanlimab in NSCLC.
Findings from the phase 3 POD1UM-304 trial (NCT04205812) supported the original sBLA.2 Findings from POD1UM-304 published in a press release in December 2024 revealed that patients who received retifanlimab plus chemotherapy experienced a median overall survival (OS) of 18.1 months compared with 13.4 months among patients treated with placebo plus chemotherapy.2 These data translated to a 25% reduction in the risk of death in favor of the investigational arm (HR, 0.75; 95% CI, 0.60-0.93; P = .0042). The median progression-free survival (PFS) was 7.7 months and 5.5 months, respectively (HR, 0.64; 95% CI, 0.52-0.79; P <.0001).
How was the POD1UM-304 study, evaluating retifanlimab in NSCLC, designed?
FDA Issues CRL for Retifanlimab Plus Chemotherapy in Metastatic NSCLC
- The FDA issued a CRL for a sBLA seeking the approval of retifanlimab injection plus platinum-containing chemotherapy for the treatment of adult patients with metastatic NSCLC.
- The FDA cited inspection findings not specific to retifanlimab at Catalent Indiana, LLC, part of Novo Nordisk, which was the third-party fill-finish facility referenced in the sBLA.
- Incyte, the developers of the agent, plan to work closely with the FDA and the Catalent Indiana facility to address the CRL and support a potential sBLA submission for retifanlimab in NSCLC.
POD1UM-304 was an international, multicenter, double-blind study that enrolled adult patients with metastatic squamous and nonsquamous NSCLC.3Patients were required to have stage IV histologically confirmed disease, have received no prior systemic treatment for advanced/metastatic NSCLC, and have measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ function.
Eligible patients were randomly assigned to the investigational or active comparator arm. In the investigational arm, patients received retifanlimab every 3 weeks on day 1 of each cycle for up to 35 cycles in combination with intravenous (IV) pemetrexed (Alimta) every 3 weeks on day 1 of each cycle or IV cisplatin (Platinol)/carboplatin (Paraplatin) every 3 weeks on day 1 of each cycle for 4 cycles. Patients in the active comparator arm received a placebo matched to the chemotherapy in combination with chemotherapy.
The primary end point was OS. Secondary end points included PFS, objective response rate (ORR), duration of response (DOR), safety, and pharmacokinetic measures.
What additional data from POD1UM-304 supported the sBLA?
The ORR in the investigational arm was 52% (95% CI, 47%-57%) compared with 39% (95% CI, 32%-46%) in the active comparator arm (P = .0012).2 The DOR values were 12.7 months (95% CI, 9.4-15.2) and 6.1 months (95% CI, 4.2-8.3), respectively.
In terms of safety, retifanlimab was generally well tolerated, and no new safety issues were reported. The most common any-grade treatment-emergent adverse effects reported in more than 10% of patients in the investigational arm included anemia (62.7%), decreased appetite (22.6%), and decreased neutrophil count (22.1%).
References
- United States Securities and Exchange Commission. Form 8-K. Incyte Corporation. February 27, 2026. Accessed March 10, 2026. https://investor.incyte.com/static-files/3e4188ba-4c55-491d-a795-18136bfac9e8
- 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. December 7, 2024. Accessed March 10, 2026. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-positive-results-phase-3-trial-evaluating
- 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://clinicaltrials.gov/study/NCT04205812
