Vibostolimab

Merck announced the discontinuation of clinical development for vibostolimab and favezelimab, anti-TIGIT and anti-LAG-3 antibodies, respectively, due to futility in Phase 3 trials for NSCLC and cHL. The decision follows DMC recommendations and data analysis, with no new safety concerns. Patients in ongoing trials may continue treatment. Merck will focus on other oncology pipeline candidates.

Merck announced the discontinuation of clinical development for vibostolimab and favezelimab, anti-TIGIT and anti-LAG-3 antibodies, respectively, after Phase 3 trials met futility criteria. The decision follows a thorough data evaluation, with no new safety concerns. Merck will focus on other oncology pipeline candidates.

Dr. Shilpa Gupta presented the study design of Cohort C of the phase II KEYNOTE-057 trial, comparing co-formulations of Vibostolimab/pembrolizumab and Favezelimab/pembrolizumab for BCG-unresponsive, high-risk NMIBC at the 2024 SUO annual meeting. The study aims to evaluate the efficacy and safety of these combinations in 60 patients with BCG-unresponsive CIS +/- papillary disease.

The phase 3 KEYVIBE-008 trial found that co-formulated vibostolimab and pembrolizumab plus etoposide and platinum did not meet the primary end point of overall survival (OS) in extensive-stage small cell lung cancer (ES-SCLC) compared to atezolizumab plus EP. Median OS was 11.5 months vs 12.9 months, and median progression-free survival (PFS) was 5.3 months vs 4.5 months. The trial was discontinued due to the benefit/risk profile, though investigation continues in non–small cell lung cancer (NSCLC).

Recent Phase II data from iTeos and GSK's anti-TIGIT therapy belrestotug plus anti-PD-1 Jemperli shows promising response rates in NSCLC patients, despite high-profile failures in the TIGIT space. Despite setbacks, companies like Roche and Merck continue TIGIT studies, emphasizing trial design's impact on outcomes. Insights suggest anti-TIGIT therapy may benefit patients with high CD-155 expression, potentially as combination therapy. Recent positive results from iTeos/GSK and Gilead/Arcus indicate a possible turning tide in TIGIT therapeutics.

GSK and iTeos Therapeutics' Phase II GALAXIES Lung-201 study showed Jemperli and belrestotug, an anti-TIGIT therapy, achieved a 60% objective response rate in non-small cell lung cancer patients, with a 30% improvement over Jemperli alone. The combination also led to significant reductions in circulating tumor DNA and was presented at ESMO 2024.

GSK and iTeos presented belrestotug + Jemperli data at ESMO 2024, showing doubled ORR in NSCLC, but lacking survival insights. Belrestotug 400mg is the RP3D for Phase III trial vs. Keytruda. TIGIT inhibitors face competition from Roche, Arcus/Gilead, and AstraZeneca, with market potential of $871m by 2030.

GSK and iTeos' anti-TIGIT antibody belrestotug, combined with GSK's PD-1 inhibitor Jemperli, showed higher objective response rates in PD-L1-positive NSCLC patients in the GALAXIES Lung-02 study, though with higher discontinuation rates and treatment-related deaths. The 400mg dose is moving to phase 3 trials.

Merck discontinues Phase 3 KeyVibe-008 trial evaluating a fixed-dose combination of vibostolimab and pembrolizumab in extensive-stage small cell lung cancer (ES-SCLC) patients due to meeting pre-specified futility criteria for overall survival (OS). Patients in the combination arm experienced higher rates of adverse events (AEs) and immune-related AEs compared to the control arm. Ongoing comprehensive analysis and further clinical development program expansions are noted.