A first-in-human phase 1b clinical trial has unveiled promising results for GT103, marking significant progress in the treatment of refractory non-small cell lung cancer (NSCLC). This innovative monoclonal antibody, engineered to target complement factor H (CFH), demonstrated safety and tolerability among patients who had exhausted other therapeutic options.
Conducted across three prominent cancer research institutions, the trial aimed to establish the safety profile and pharmacokinetics of GT103, as well as to identify the maximum tolerated dose (MTD). With NSCLC presenting formidable treatment challenges, particularly for patients with advanced disease, the introduction of such targeted therapies is hoped to change the therapeutic paradigm.
From June 2020 until December 2023, 31 patients with refractory NSCLC were enrolled to receive GT103 intravenously, with dose escalation following the “3 + 3” schema. Enrolled patients had previously undergone multiple lines of therapy, emphasizing the urgent need for effective alternatives. Notably, the median age of patients was 63 years, predominantly male, with adenocarcinoma histology being the most common.
The researchers presented their findings, confirming GT103's overall safety. While no adverse dose-limiting toxicities were recorded at higher doses, two grade 3 acute kidney injury and grade 2 colitis events were documented at lower dosages. Fortunately, these incidents were resolved without any long-term complications.
Key results indicated no objective responses were observed; yet, stable disease was achieved by 9 patients, resulting in approximately 29% of the cohort experiencing some degree of therapy stabilization. The median overall survival across the trial participants was reported as 25.7 weeks, showcasing at least modest clinical potential.
The pharmacokinetic analysis of GT103 indicated it possesses an estimated half-life of 6.5 days, providing insights on dosing intervals moving forward. This characteristic is aligned with expectations for IgG3 monoclonal antibodies, which often outperform other classes in complement fixation—a mechanism seen as beneficial for achieving improved tumor targeting and subsequent immune activation.
Additional exploratory analyses highlighted potential predictive biomarkers for patient response, indicating patients with certain tumor mutations may experience longer progression-free survival. While no statistically significant associations were identified, these early observations generate enthusiasm for future studies.
This trial did not include any control group, and as such, efficacy must be cautiously interpreted against the backdrop of palliative treatment histories. Nevertheless, the lack of off-target toxicity and GT103's favorable safety profile suggest it could serve as synergistic therapy, especially when combined with existing treatment modalities like immune checkpoint inhibitors.
Moving forward, the research team plans to conduct larger, randomized trials, including combinations of GT103 with pembrolizumab to evaluate enhanced efficacy against NSCLC. The clinical community's focus remains committed to unraveling the underlying mechanisms governing the immune response and refining therapies to prolong survival for this challenging patient population.
Overall, this initial phase 1b trial has laid the groundwork for future investigation, offering hope for innovative approaches to combat NSCLC and improve patient outcomes.