The GALAXIES Lung-201 (NCT05565378) Phase II study evaluated the combination of belrestotug (an anti-TIGIT antibody) with dostarlimab (an anti–PD-1 agent) in patients with previously untreated, locally advanced/metastatic (LA/M) PD-L1 high (TPS ≥ 50%) NSCLC. The trial sought to address the unmet need for novel therapies in this subgroup, as less than half of patients with unresectable PD-L1 high NSCLC respond to first-line immunotherapy.

Participants were randomized into four groups: dostarlimab alone or dostarlimab combined with one of three different doses of belrestotug (100 mg, 400 mg, or 1000 mg) administered every three weeks. The primary endpoint was the objective response rate (ORR).

This interim analysis, based on a median follow-up of 7.3 months, demonstrated promising results for the combination therapy:

• ORR: The ORR was notably higher in the combination groups (63.3% to 76.7%) compared to dostarlimab alone (37.5%).

• Confirmed ORR: The confirmed ORR ranged from 59.4% to 63.3% in the combination arms, compared to 28.1% for dostarlimab alone.

• Safety: The treatment-related adverse events (TRAEs) were dose-dependent, with the 1000 mg group experiencing the highest rate of Grade 3+ TRAEs (43%). However, these were considered manageable.

KOL insights

“The follow-up interim analysis from the GALAXIES Lung-201 study represent promising progress and the deep responses observed in the belrestotug + dostarlimab doublet provide a strong, consistent signal. We eagerly anticipate gaining further insights from this trial over the next year as the dataset matures."-  Clinical Researcher and Investigator, EU

“In the process of identifying if these combos raise the bar in NSCLC, the question remains on targeting LAG3 and TIGIT in NSCLC”- Professor of Medical Oncology, John Hopkins University

Conclusion 

Belrestotug combined with dostarlimab exhibited clinically meaningful anti-tumor activity in patients with previously untreated PD-L1 high NSCLC. The manageable safety profile across all dosage levels supports further exploration of this combination, particularly in those not responding well to standard PD-1 inhibitors.

Currently, around 70% of patients with first-line PD-L1 high NSCLC seek chemotherapy-free regimens, reflecting the demand for more targeted and less toxic therapeutic options. The belrestotug-dostarlimab combination, as seen in the GALAXIES study, holds the potential to reshape the treatment paradigm in this population. By potentially improving response rates while maintaining a manageable safety profile, this doublet could set new benchmarks in a setting where therapeutic advancements are highly needed.

Initiating the Phase III program will be a pivotal step, not just for validating these promising results but also for laying the groundwork to establish a broader franchise in NSCLC treatment. As immunotherapy continues to evolve, this combination therapy could play a transformative role in addressing the unmet needs of patients who are unsuitable for chemotherapy, pushing the frontier of precision oncology further.