A Phase II study of GT103 in combination with pembrolizumab in refractory, metastatic non–small cell lung cancer

Abstract Background Treatment options for patients with advanced non–small cell lung cancer (NSCLC) with disease progression following immune checkpoint inhibitor (ICI) and platinum‐based chemotherapy are limited. GT103 is a fully human immunoglobulin G3 monoclonal antibody targeting complement factor H, which promotes antitumor immunity. In a Phase I study, GT103 was well tolerated and maximum tolerated dose was not reached. Methods A single arm, Simon two‐stage, Phase II study was conducted that evaluated efficacy and safety of GT103 plus pembrolizumab in patients with advanced NSCLC who have had progression on up to two lines of therapy, including an ICI. Patients with actionable genomic drivers were eligible if they had received at least one targeted therapy. Patients received GT103 10 mg/kg and pembrolizumab 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Primary objectives were safety and objective response rate. Secondary objectives were overall survival and progression‐free survival. Results Twenty‐one patients were enrolled. Most common treatment‐related adverse events occurring in ≥10% of patients were fatigue (24%, n = 5) and decreased lymphocyte count (24%, n = 5). One patient experienced grade 3 treatment‐related adverse events, including pneumonitis and decreased lymphocyte count. Objective response rate was 10% (95% CI, 1–30) with two objective responses (1 complete response (CR), 1 partial response (PR)). Disease control rate (= CR + PR + stable disease (SD)) was 67% ( n = 14). Four patients (19%) experienced disease control for over 9 months. Median progression‐free survival was 2.6 months (95% CI, 1.4–4.0) and median overall survival was 10.3 months (95% CI, 6.6–NE). Conclusion Combination of GT103 with pembrolizumab was well tolerated with no new safety signals. A subset of patients experienced durable responses and disease control despite prior exposure to ICI.