Vibostolimab/Pembrolizumab Fails to Reach Statistical Significance in NSCLC

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Vibostolimab, an anti-TGIT antibody, and pembrolizumab (Keytruda) plus docetaxel improved progression-free survival (PFS) by 2.4 months compared with docetaxel alone in patients with previously treated metastatic non–small cell lung cancer (NSCLC); however, the results were not statistically significant, according to findings presented at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2023.^1,2

Findings from the KeyVibe-002 trial (NCT04725188) showed that vibostolimab with pembrolizumab and docetaxel demonstrated a median PFS of 5.6 months compared with 3.2 months with docetaxel alone (HR, 0.77; 95% CI, 0.53-1.13; P =.0910). Further, the combination of vibostolimab and pembrolizumab alone did not increase median PFS compared with docetaxel alone (2.7 months v 3.2 months [HR, 1.40; 95% CI, 0.96-2.02; P =.9622).

Investigators also presented data from key secondary end points at ESMO IO. Vibostolimab/pembrolizumab and docetaxel improved overall survival (OS) compared with docetaxel alone at 10.2 months (95% CI, 8.6-14.9) vs 8.8 months (95% CI, 6.4-11.1). However, the improvement also did not meet statistical significance (HR, 0.76; 95% CI, 0.50-1.15). Moreover, vibostolimab and pembrolizumab alone did not improve OS compared with docetaxel alone (7.5 months [95% CI, 5.2-13.4] v 8.8 months; HR, 1.05; 95% CI, 0.70-1.58).

Patients given vibostolimab and pembrolizumab plus docetaxel had an overall response rate (ORR) of 29.9% (95% CI, 20.5%-40.6%). The ORR for vibostolimab and pembrolizumab alone was 6.0% (95% CI, 2.0%-13.5%) and 15.3% (95% CI, 8.4%-24.7%) for docetaxel alone. The median duration of response was 6.5 months (range, 2.1-15.4+ months) with vibostolimab, pembrolizumab, and docetaxel, not reached (NR) with vibostolimab and pembrolizumab alone (range, 2.6-6.2+ months), and NR with docetaxel alone (range, 1.6-11.1+ months).

“This study was designed to evaluate a coformulation of vibostolimab and pembrolizumab in a population of patients who are heavily pre-treated and have progressed following treatment with standard of care therapies, often leaving them with limited treatment options and a poor prognosis,” said Scot Ebbinghaus, MD, vice president, global clinical development, Merck Research Laboratories, in a press release.¹ “We will leverage our evolving understanding of novel combinations and coformulations to help inform our comprehensive research program evaluating this coformulation across a wide range of tumor types.”

Regarding safety, no new safety signals were identified, and the safety profiles were consistent with the known profiles of the individual agents. Immune-mediate adverse events (AEs) and infusion reactions were observed in 29.4% of patients in the vibostolimab/pembrolizumab plus docetaxel arm, 20.5% in the vibostolimab/pembrolizumab arm, and 12% in the docetaxel arm.

Treatment-related deaths occurred in 4 patients in the vibostolimab/pembrolizumab plus docetaxel arm and 1 patient each in the vibostolimab/pembrolizumab and docetaxel arms. All-grade treatment-related AEs (TRAEs) occurred in 60.2% of the vibostolimab/pembrolizumab only arm, 89.2% of the docetaxel arm, and 96.5% of the vibostolimab/pembrolizumab plus docetaxel arm.

The most common grade 3 or higher TRAEs in the vibostolimab/pembrolizumab plus docetaxel arm were neutropenia (16.5%), anemia (7.1%), and asthenia (4.7%). For the vibostolimab and pembrolizumab arm, the most common grade 3 or higher TRAEs were asthenia (2.4%) and diarrhea (2.4%). Further, neutropenia (14.5%) and anemia (6.0%) were the most common severe TRAEs in the docetaxel arm.^1,2

REFERENCES:

1. Merck announces findings from phase 2 KeyVibe-002 trial evaluating an investigational coformulation of vibostolimab and pembrolizumab in previously treated patients with metastatic non–small cell lung cancer (NSCLC). News release. Merck. December 7, 2023. Accessed December 8, 2023. https://tinyurl.com/3z8wdet2

2. Peled, N. MK-7684A (vibostolimab [vibo] plus pembrolizumab [pembro] coformulation) with/without docetaxel in metastatic NSCLC after platinum-chemotherapy (chemo) and immunotherapy. Presented at ESMO IO Congress. December 6-8, 2023. Geneva, Switzerland. Abstract 121P.