On December 7, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported full results from the non-registrational Phase 2 KeyVibe-002 trial evaluating vibostolimab/pembrolizumab, an investigational coformulation of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA), Merck’s anti-PD-1 therapy, with or without docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progressive disease after treatment with immunotherapy and platinum-doublet chemotherapy (Press release, Merck & Co, DEC 7, 2023, View Source [SID1234638245]). These results are being presented today during a poster session at the 2023 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology (I-O) Annual Congress (abstract #121P).
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"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"
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Data presented at ESMO (Free ESMO Whitepaper) I-O showed that vibostolimab/pembrolizumab plus docetaxel extended median progression-free survival (PFS) by 2.4 months compared to those treated with docetaxel alone, though the results did not reach statistical significance (5.6 months vs. 3.2 months; HR=0.77 [95% CI, 0.53-1.13]; p=0.0910). Vibostolimab/pembrolizumab alone did not show an improvement in median PFS compared to docetaxel alone (2.7 months vs. 3.2 months; HR=1.40 [95% CI, 0.96-2.02]; p=0.9622).
"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 Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. "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."
Data from key secondary endpoints, including overall survival (OS), overall response rate (ORR) and duration of response (DOR) were also presented. Vibostolimab/pembrolizumab plus docetaxel improved OS compared with docetaxel alone, though these results did not reach statistical significance (HR=0.76 [95% CI, 0.50-1.15]). Vibostolimab/pembrolizumab alone did not show an improvement in OS compared to docetaxel alone (HR=1.05 [95% CI, 0.70-1.58). The median OS for vibostolimab/pembrolizumab plus docetaxel was 10.2 months (95% CI, 8.6-14.9), 7.5 months (95% CI, 5.2-13.4) for vibostolimab/pembrolizumab alone and 8.8 months (95% CI, 6.4-11.1) for docetaxel. The ORR for patients receiving vibostolimab/pembrolizumab plus docetaxel was 29.9% (95% CI, 20.5-40.6), 6.0% (95% CI, 2.0-13.5) for vibostolimab/pembrolizumab alone and 15.3% (95% CI, 8.4-24.7) for docetaxel. Median DOR was 6.5 months (range, 2.1+ to 15.4+ months) for the vibostolimab/pembrolizumab plus docetaxel arm. Median DOR was not reached for the vibostolimab/pembrolizumab arm (range, 2.6+ to 6.2+ months) and for the docetaxel arm (range, 1.6 to 11.1+ months).
The safety profile of vibostolimab/pembrolizumab was consistent with that observed for vibostolimab and pembrolizumab in previously reported studies, with no new safety signals observed. Immune-mediated adverse events and infusion reactions occurred in 29.4% of patients who received vibostolimab/pembrolizumab plus docetaxel, 20.5% of those who received vibostolimab/pembrolizumab alone and 12% of those who received docetaxel alone. There were four treatment-related deaths in the vibostolimab/pembrolizumab plus docetaxel arm of the study, and one in each of the vibostolimab/pembrolizumab and docetaxel only arms. In the vibostolimab/pembrolizumab only arm of the study, there was a lower incidence of treatment-related adverse events (TRAEs) of any grade compared to the docetaxel only arm (60.2% vs. 89.2%), and 96.5% of patients in the vibostolimab/pembrolizumab plus docetaxel arm had TRAEs. The most common severe (grade 3-5) TRAEs in the study were neutropenia (16.5%), anemia (7.1%) and asthenia (4.7%) for treatment with vibostolimab/pembrolizumab plus docetaxel; asthenia (2.4%) and diarrhea (2.4%) for vibostolimab/pembrolizumab alone and neutropenia (14.5%) and anemia (6.0%) for docetaxel alone.
Vibostolimab is Merck’s investigational anti-TIGIT antibody that restores antitumor activity by blocking the TIGIT receptor from binding to its ligands (CD112 and CD155), thereby activating T lymphocytes that help destroy tumor cells. Merck has an extensive clinical development program evaluating the safety and efficacy of the vibostolimab/pembrolizumab coformulation alone and in combination with other agents in over 4,000 patients. Ongoing Phase 3 studies in lung cancer include KeyVibe-003, KeyVibe-006, KeyVibe-007 and KeyVibe-008, as well as KeyVibe-010 in melanoma.
About KeyVibe-002
KeyVibe-002 is a randomized, partially blind Phase 2 trial (ClinicalTrials.gov, NCT04725188) evaluating vibostolimab/pembrolizumab, a coformulation of vibostolimab and pembrolizumab, with or without docetaxel versus placebo plus docetaxel in patients with metastatic NSCLC with progressive disease after treatment with immunotherapy and platinum-doublet chemotherapy. The trial’s primary endpoint is PFS, as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Key secondary endpoints include OS and ORR, as assessed by BICR per RECIST v1.1. The study enrolled 255 patients who were randomly assigned in three separate study arms (1:1:1) to receive either:
Arm 1 (Blinded): Vibostolimab/pembrolizumab (pembrolizumab 200 mg plus vibostolimab 200 mg/20 mL intravenously [IV] every 3 three weeks [Q3W] until a discontinuation criterion is met or completion of 35 cycles) plus docetaxel (75 mg/m2 IV Q3W until a discontinuation criterion is met or as per approved local label); or
Arm 2 (Open-label): Vibostolimab/pembrolizumab (pembrolizumab 200 mg plus vibostolimab 200 mg/20 mL IV Q3W until a discontinuation criterion is met or completion of 35 cycles); or
Arm 3 (Placebo-blinded): Placebo (saline IV Q3W) plus docetaxel (75 mg/m2 IV Q3W until a discontinuation criterion is met or as per approved local label).
KeyVibe-002, a non-registrational study, was designed with two primary objectives: 1) to evaluate the efficacy of vibostolimab/pembrolizumab alone compared with docetaxel, a standard of care; and 2) in a blinded assessment, evaluate the efficacy of adding vibostolimab/pembrolizumab to docetaxel, compared with docetaxel alone.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and approximately 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 26.2%, which is a 22% improvement over the last five years. Improved survival rates are due, in part, to advances in diagnostic and surgical procedures, as well as the introduction of new therapies. However, screening, early detection and improving treatment rates remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 4.5% of people in the U.S. who are eligible were screened for lung cancer in 2022.