GSK and iTeos' anti-TIGIT antibody, belrestotug, has shown encouraging efficacy in a phase 2 trial for PD-L1-positive non-small cell lung cancer (NSCLC), offering renewed optimism for the TIGIT class of therapies. The GALAXIES Lung-02 study, presented at the ESMO congress in Barcelona, revealed that belrestotug, when added to GSK's PD-1 inhibitor Jemperli (dostarlimab), achieved a higher objective response rate (ORR) compared to Jemperli alone.
Efficacy and Dosage
The GALAXIES Lung-02 trial enrolled patients with previously untreated, locally advanced or metastatic PD-L1-high (50% or greater) NSCLC unsuitable for surgery. The study also included arms evaluating belrestotug with MSD's Keytruda (pembrolizumab) and Keytruda alone, though those data were not presented at ESMO. Results indicated a dose-response relationship with belrestotug: the lowest dose (100mg) yielded a 63.3% ORR, the middle dose (400mg) a 65.6% ORR, and the highest dose (1,000mg) a 76.7% ORR, compared to 28.1% for Jemperli alone.
Safety Profile
According to iTeos, side effects were "generally manageable" but more frequent in the combination therapy groups (84%) than with Jemperli alone (59%). These included typical immunotherapy-related issues such as skin disorders and endocrine disorders. However, discontinuation rates were notably higher with belrestotug (16% to 40%) compared to Jemperli monotherapy (6%), and three treatment-related deaths occurred in the belrestotug group. For context, the KEYNOTE-042 trial, which established Keytruda monotherapy as a standard of care for PD-L1-high NSCLC, reported a 44.8% response rate compared to 27.8% for chemotherapy.
TIGIT Landscape and Future Trials
These results are particularly significant given the setbacks experienced by other TIGIT therapies, including disappointing outcomes for MSD's vibostolimab and Roche's tiragolumab. Michel Detheux, CEO of iTeos, stated, "With roughly 60% confirmed ORR at three distinct doses and a meaningful difference of 30% compared to dostarlimab alone, we believe this underscores the potential differentiation of our TIGIT:PD-1 doublet."
The 400mg dose of belrestotug has been selected for a phase 3 trial, GALAXIES-Lung-301, in first-line patients. This trial will compare belrestotug plus Jemperli to Keytruda plus placebo. While the phase 2 results are promising, it is important to note that ORR improvements can diminish in larger, late-stage trials, and survival data are still pending. GSK licensed rights to belrestotug in 2021 for an upfront payment of $625 million, in a deal potentially worth $2 billion overall.
