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

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.