TIGIT Setback Continues: Vibostolimab-Pembrolizumab Combo Shows Disappointing Efficacy in NSCLC

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On December 7, 2023, MSD announcedResults of the Non-registered Phase 2 KeyVibe-002 Clinical Trial, Which Aimed to Evaluate Vibostolimab(Anti-TIGIT antibody) andPembrolizumab (anti-PD-1 antibody), with or without docetaxel, forImmunotherapy and platinum-based doublet chemotherapyPatients with metastatic non-small cell lung cancer (NSCLC) whose condition has progressed.

Compared with single useDocetaxelCompared to treatment, the combination of vibostolimab and pembrolizumab (V/P)DocetaxelThe median progression-free survival (PFS) was extended by 2.4 months, but the result did not reach statistical significance (5.6 months vs. 3.2 months; HR= 0.77 [95% CI, 0.53-1.13]; p=0.0910). Compared with docetaxel alone, single-agent useV/PThe treatment group did not show an improvement in median PFS (2.7 months vs. 3.2 months; HR=1.40 [95% CI, 0.96-2.02]; p=0.9622).

MSD also disclosed key secondary endpoint data, including Overall Survival (OS), Overall Response Rate (ORR), and Duration of Response (DOR). Compared with docetaxel alone, V/PCombination with docetaxel improved OS but likewise did not reach statistical significance (HR=0.76 [95% CI, 0.50-1.15]). Compared with docetaxel alone, the use of V/PNo improvement in OS was observed (HR=1.05 [95% CI, 0.70-1.58]).V/PThe median OS for docetaxel was 10.2 months, using V/PGroupThe median OS was 7.5 months, and 8.8 months for docetaxel. Received V/PThe ORR of patients treated with docetaxel was 29.9%, usingV/PThe ORR of patients was 6.0%, and the ORR of patients using docetaxel was 15.3%.V/PThe median DOR in the docetaxel group was 6.5 months. V/PThe median DOR was not reached in the combination group and the docetaxel group.

V/PThe safety profile was consistent with the safety profiles of vibostolimab and pembrolizumab observed in previously reported studies, with no new safety signals identified.

Although the enrollment criteria were stringent, involving patients with advancements in immunotherapy, it also proved one thing: TIGIT/PD-1 dual immunotherapy challenging PD-1 inhibitor resistance in patients is not a very realistic endeavor.

Nowadays, immunotherapy has encountered a bottleneck, and the combination of IO and ADC has become the main R&D trend. IO mainly refers to PD-1 inhibitors, and there is a growing trend that PD-1/VEGF will gradually become the second-generation PD-1 inhibitor, replacing PD-1 monoclonal antibodies and further combined with ADC.