1487 Results from a phase II study of GT103 in combination with pembrolizumab in refractory, metastatic non-small cell lung cancer

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Background GT103 is a fully human IgG3 monoclonal antibody targeting complement factor H (CFH) and binds to a cryptic epitope of the protein promoting tumor cell death and anti-tumor immune response. A phase I trial of GT103 monotherapy has demonstrated the therapy to be well tolerated in advanced NSCLC patients. Preclinical data suggests combination with immune checkpoint therapy may improve antitumor activity. Methods The study utilized a 10-patient safety lead-in of GT103 in combination with pembrolizumab, followed by a response assessment using Simon’s optimal two-stage design. Eligible patients must have received 1–2 lines of prior treatment with chemotherapy and immunotherapy. Patients received GT103 10mg/kg and pembrolizumab 200 mg IV every 3 weeks. The study tested the null hypothesis that P ≤ 0.10 where P is the true though unknown radiographic response rate vs the alternative hypothesis P ≥ 0.25 with 90% power assuming type I error of 0.10. The planned sample size was 21 patients in stage 1 and 29 patients in stage 2; 3 or more responses were needed to progress to stage 2. We present results from a planned interim analysis of stage I. Results As of August 8, 2024, 21 patients were enrolled and received study treatment. One patient died during cycle 1 (unrelated to treatment) and 20 patients received efficacy evaluation; all 21 patients are included in the interim analysis. No DLTs were identified in the safety lead in phase and no grade 4 or 5 AEs were reported during the course of the study. Five patients experienced grade 3 SAEs unrelated to the treatment drugs. Treatment related toxicity was mostly grade 1–2; 1 patient experienced grade 3 lymphocyte decrease and 1 patient experience grade 3 pneumonitis. Two objective responses were seen (1 CR and 1 PR). Fourteen patients (66%) experienced disease control (CR, PR, SD), and 91.7% disease control in patients without an activating mutation (n=12). Median PFS was 2.6 months. Median OS has not been reached; median follow up among 12 alive patients was 9.3 months (range 4.4 to 14.1 months). Four patients remained on treatment beyond 7 months. Conclusions The combination of GT103 and pembrolizumab was safe and well-tolerated. The combination did not meet prespecified criteria to proceed with stage 2 of the study, however 2 responses and disease control in 66% of patients were noted. Updated trial results will be shown at time of presentation. Acknowledgements The authors appreciate the efforts of DSMB members: Drs Mary Redman, Martin Edelman, and Shirish Gadgeel. Grid Therapeutics for drug and financial support for the study. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,Rahway, NJ, USA provided pembrolizumab and financial support for the study. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck. Trial Registration Trial Registration: NCT05617313. Ethics Approval The institutional review board of the participating centers approved the study, and this trial was conducted in accordance with Good Clinical Practice guidelines and the provisions of the Declaration of Helsinki. Patients were required to provide informed consent before any study-related procedures.

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