GSK and iTeos' Jemperli-Belrestotug Combo Shows Promise in NSCLC
核心洞察
GSK and iTeos' combination of Jemperli and belrestotug demonstrated a confirmed objective response rate of approximately 60% in NSCLC (搜索) patients.
Circulating tumor DNA levels decreased significantly in patients receiving the combination therapy compared to Jemperli alone, indicating a deeper response.
The GALAXIES Lung-201 study showed manageable immune-related adverse events with the doublet therapy, supporting its potential for further development.
GSK and iTeos Therapeutics announced promising Phase II results for their combination therapy of Jemperli (dostarlimab) and belrestotug in patients with non-small cell lung cancer (搜索) (NSCLC (搜索)). The GALAXIES Lung-201 study revealed a confirmed objective response rate of approximately 60% across all doses, marking a potential advancement in NSCLC treatment. These findings were presented at the 2024 European Society for Medical Oncology Congress (ESMO 2024).
Enhanced Tumor Response with Combination Therapy
The Phase II GALAXIES Lung-201 study evaluated the efficacy and safety of Jemperli plus belrestotug in NSCLC (搜索) patients with high PD-L1 (搜索) expression who had not received prior treatment. The data indicated a clinically meaningful improvement, with an approximate 30% increase in objective response rate compared to Jemperli monotherapy. Michel Detheux, iTeos’ president and CEO, highlighted the “potential differentiation” of combining an anti-TIGIT (搜索) therapy with a PD-1 treatment.
Significant Reduction in ctDNA Levels
Beyond objective response rates, the combination therapy demonstrated a notable impact on circulating tumor DNA (ctDNA) levels. Patients receiving 400 mg and 1,000 mg of belrestotug experienced a 94% and 97% reduction in ctDNA from baseline to week 7, respectively. In contrast, Jemperli monotherapy resulted in a 65% reduction in ctDNA during the same period. This suggests a deeper and more comprehensive tumor response with the combination treatment.
Safety and Tolerability
The GALAXIES Lung-201 study also assessed the safety profile of the Jemperli-belrestotug combination. Results indicated higher rates of immune-related adverse events with the doublet therapy; however, these events were generally manageable. Common treatment-related toxicities included skin and subcutaneous disorders, as well as endocrine disorders. These findings are crucial for understanding the risk-benefit profile of the combination therapy.
Ongoing Phase III Trial
Building on the Phase II results, GSK and iTeos have initiated the GALAXIES Lung-301 study, a Phase III trial designed to further evaluate the Jemperli-belrestotug combination in the same treatment setting and patient population. This study aims to support registration efforts and potentially establish a new standard of care for PD-L1 (搜索) high NSCLC (搜索) patients.
Belrestotug Mechanism of Action
Belrestotug is an IgG1 monoclonal antibody that targets TIGIT (搜索), an inhibitory receptor that cancer cells use to suppress immune responses. By blocking TIGIT, belrestotug enhances the body’s anti-tumor response, promoting cytokine release and activating antibody-dependent cell-killing mechanisms. This mechanism is designed to reinvigorate the immune system's ability to fight cancer.
TIGIT Landscape
The TIGIT (搜索) space has faced recent setbacks, with Merck halting its Phase III melanoma program for vibostolimab and Roche ending a Phase II/III study for tiragolumab. BMS also returned rights to Agenus for the anti-TIGIT bispecific antibody AGEN1777. The positive results from the GALAXIES Lung-201 study offer renewed enthusiasm for TIGIT-targeted therapies, suggesting potential for belrestotug in NSCLC (搜索) treatment.