A LARGE phase 3 trial has found that adding the PD-1 inhibitor retifanlimab to platinum-based chemotherapy significantly improved overall survival in patients with metastatic non-small-cell lung cancer (NSCLC), compared with chemotherapy alone.
Trial design highlights broad patient population
The POD1UM-304 study enrolled 583 adults with Stage IV squamous or non-squamous NSCLC who had not received prior systemic therapy. Patients were randomised 2:1 to receive retifanlimab or placebo alongside standard platinum-based chemotherapy, tailored to tumour histology. Treatment continued for up to 2 years unless disease progression, toxicity, or consent withdrawal occurred. The primary endpoint was overall survival, assessed in the full analysis set.
Survival benefit confirmed with retifanlimab NSCLC treatment
Median overall survival was 18.1 months with retifanlimab plus chemotherapy compared with 13.4 months in the placebo group (hazard ratio: 0.75; 95% CI: 0.60–0.93; p=0.0042). The benefit was observed across squamous and non-squamous histologies. Safety outcomes were consistent with prior PD-1 inhibitor-chemotherapy combinations, though the retifanlimab group experienced higher rates of Grade ≥3 treatment-related adverse events (61% vs 54%), serious events (41% vs 30%), and dose delays or discontinuations. COVID-19-related fatalities were similar between groups.
Implications for first-line NSCLC management
The findings position retifanlimab plus chemotherapy as a potential new option for first-line treatment of metastatic NSCLC, complementing existing PD-1 and PD-L1 inhibitor regimens. Investigators emphasised that the therapy’s efficacy and manageable safety profile underscore its relevance for both squamous and non-squamous subtypes, addressing a broad patient population.
If confirmed in ongoing analyses, retifanlimab could join the expanding range of immunotherapy-chemotherapy combinations that have reshaped the NSCLC treatment landscape over the past decade.
Reference
Lu S et al. Retifanlimab versus placebo in combination with platinum-based chemotherapy in patients with first-line non-squamous or squamous metastatic non-small-cell lung cancer (POD1UM-304): a phase 3, multiregional, placebo-controlled, double-blind, randomised study. Lancet Respir Med. 2025; DOI:10.1016/S2213-2600(25)00209-7.
