Merck has announced results from its non-registrational Phase 2 KeyVibe-002 trial investigating a novel immunotherapy combination for advanced non-small cell lung cancer (NSCLC) at the 2023 European Society of Medical Oncology (ESMO) Immuno-Oncology Annual Congress.
The study evaluated a coformulation of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA®) in patients with metastatic NSCLC who had progressed after immunotherapy and platinum-doublet chemotherapy. The trial compared the combination with and without docetaxel against docetaxel alone.
The vibostolimab/pembrolizumab plus docetaxel arm demonstrated a median progression-free survival (PFS) of 5.6 months compared to 3.2 months with docetaxel alone, though this difference did not reach statistical significance (HR=0.77 [95% CI, 0.53-1.13]; p=0.0910). The combination without docetaxel showed no improvement in PFS compared to docetaxel (2.7 months vs. 3.2 months).
Secondary endpoint data revealed trends favoring the triple combination, with overall survival of 10.2 months for vibostolimab/pembrolizumab plus docetaxel versus 8.8 months for docetaxel alone (HR=0.76 [95% CI, 0.50-1.15]). The overall response rate was notably higher in the triple combination arm at 29.9% compared to 15.3% with docetaxel alone.
"This study targeted a heavily pre-treated patient population with limited treatment options and poor prognosis," said Dr. Scot Ebbinghaus, vice president of global clinical development at Merck Research Laboratories. "The insights gained will help inform our comprehensive research program evaluating this coformulation across various tumor types."
Safety analysis showed immune-mediated adverse events occurred in 29.4% of patients receiving the triple combination, compared to 20.5% with the dual combination and 12% with docetaxel alone. The most common severe treatment-related adverse events in the triple combination arm were neutropenia (16.5%), anemia (7.1%), and asthenia (4.7%).
The trial enrolled 255 patients randomized across three arms: vibostolimab/pembrolizumab plus docetaxel, vibostolimab/pembrolizumab alone, or docetaxel alone. Merck continues to evaluate this novel immunotherapy combination through multiple Phase 3 studies, including KeyVibe-003, KeyVibe-006, KeyVibe-007, KeyVibe-008 in lung cancer, and KeyVibe-010 in melanoma.
Mechanism of Action and Development Program
Vibostolimab works by blocking the TIGIT receptor from binding to its ligands (CD112 and CD155), thereby activating T lymphocytes to help destroy tumor cells. The ongoing clinical development program is evaluating the vibostolimab/pembrolizumab coformulation alone and in combination with other agents in over 4,000 patients across multiple tumor types.
Disease Burden and Unmet Need
Lung cancer remains the leading cause of cancer death worldwide, with over 2.2 million new cases and approximately 1.8 million deaths in 2020. NSCLC accounts for about 81% of all lung cancer cases. While the five-year survival rate has improved by 22% over the last five years to 26.2% in the U.S., significant unmet needs remain, particularly in advanced disease settings where new treatment options are critically needed.
