Phase II Study of Cisplatin/Gemcitabine Plus Necitumumab for Squamous NSCLC After ICI‐Platinum Therapy (WJOG14120L)

ABSTRACT Treatment options remain limited for unresectable or advanced lung squamous cell carcinoma (LSqCC) that progresses after immune checkpoint inhibitor (ICI)‐based therapy. Although combination therapy with cisplatin, gemcitabine, and necitumumab (CGN) represents a potential second‐line regimen, no prospective data in a post‐ICI setting have been reported. This open‐label, multicenter single‐arm Phase II study enrolled patients with LSqCC after platinum‐based chemotherapy plus ICI, including concurrent chemoradiotherapy. The primary endpoint was objective response rate (ORR), with the null and alternative hypotheses set at 23% and 40%, respectively. Secondary endpoints included the disease‐control rate (DCR), progression‐free survival (PFS), overall survival (OS), the impact of platinum‐free interval (PFI), eligibility for anti‐angiogenic therapies, and safety. Forty‐six patients were evaluable for efficacy. ORR was 26.1% (80% CI, 17.7–36.2) and DCR was 87.0% (95% CI, 73.7–95.1). Median PFS and OS were 4.4 months (95% CI, 4.1–5.5) and 12.2 months (95% CI, 9.4–15.2), respectively. Common adverse events included hematological toxicities, acneiform rash, and hypomagnesemia. No pneumonitis or treatment‐related deaths were observed. The safety profile was consistent across prior treatment types and anti‐angiogenic therapies eligibility. PFI analysis showed that longer PFI durations were associated with improvements in PFS and OS, and the optimal PFI cutoff value was approximately 4 months. Although the predefined response threshold was not met, CGN demonstrated modest antitumor activity with a high DCR and a manageable toxicity after ICI‐based therapy. CGN may be a feasible treatment option for second‐line after ICI‐based therapy, including for patients unsuitable for anti‐angiogenic therapies, although further validation is warranted. Trial Registration: jRCTs051200138