A groundbreaking clinical trial has revealed promising results for GT103, a novel complement factor H targeting antibody, in treating patients with refractory non-small cell lung cancer (NSCLC). The study, designated as TOP1902, was conducted across three prestigious cancer centers: Duke Cancer Institute, Karmanos Cancer Institute, and H Lee Moffitt Cancer Center.
Trial Design and Patient Population
The first-in-human dose escalation trial employed a traditional "3+3" schema, evaluating GT103 at multiple dose levels ranging from 0.3 mg/kg to 15 mg/kg. Treatment was administered intravenously every three weeks, with an additional cohort receiving 10 mg/kg every two weeks.
Eligible participants included adults with advanced stage III, IV, or recurrent NSCLC who had experienced disease progression following standard care therapy. All patients had previously received both immunotherapy (anti-PD-1/PD-L1) and platinum-based chemotherapy. For patients with EGFR, ALK, or ROS1 alterations, prior treatment with at least one tyrosine kinase inhibitor was required.
Safety and Assessment Protocol
The trial implemented rigorous safety monitoring, with assessments conducted weekly during the first cycle of the dose escalation cohort. Patients underwent comprehensive evaluations including vital signs, ECOG performance status, physical examinations, and detailed laboratory analyses. Tumor response was evaluated using RECIST version 1.1 and iRECIST criteria through independent review.
Innovative Mechanism and Clinical Implications
GT103's unique mechanism of action sets it apart from traditional chemotherapy approaches. The antibody not only targets tumor cell death but also promotes a robust immune response. This dual action results in reduced viable tumor cells and increased immune cell infiltration, though these effects may not always translate to significant changes in tumor size on imaging.
Pharmacokinetic Analysis
The study incorporated detailed pharmacokinetic (PK) analysis using plasma samples collected at multiple timepoints. GT103 concentrations were measured using an indirect ELISA method, with PK parameters analyzed through a population approach using Phoenix NLME software. The analysis explored various compartment models to understand the drug's behavior in the body.
Biomarker Assessment
To evaluate complement system involvement, researchers analyzed baseline serum complement activity and monitored soluble C5b-9 concentrations as a potential pharmacodynamic marker. These measurements provided crucial insights into the complement cascade's role in treatment response.
The trial represents a significant advancement in complement-targeted therapy for NSCLC, offering a novel approach for patients who have exhausted standard treatment options. While the study was closed to enrollment before completing the highest dose levels, this decision was based on competing studies and projected timelines rather than safety concerns.
