Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the discontinuation of the vibostolimab and pembrolizumab coformulation arm of the Phase 3 KeyVibe-010 trial. The trial is evaluating the investigational coformulation of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA®), Merck’s anti-PD-1 therapy, compared to KEYTRUDA alone, as adjuvant treatment for patients with resected high-risk melanoma (Stage IIB-IV). At a pre-planned analysis, data showed that the primary endpoint of recurrence-free survival (RFS) met the pre-specified futility criteria. A higher rate of discontinuation of all adjuvant therapy by patients in the coformulation arm versus the KEYTRUDA-only arm, primarily due to immune-mediated adverse experiences, rendered it highly unlikely that the trial could achieve a statistically significant improvement in RFS. Based on the recommendation of an independent Data Monitoring Committee (DMC), Merck is unblinding the study and recommends that patients receiving the vibostolimab and pembrolizumab coformulation be offered the option to be treated with KEYTRUDA monotherapy. Data analysis from this study is ongoing. Results will be shared with the scientific community and communicated to regulatory agencies.
“Through our clinical development program, we continue to ask the tough questions in an effort to fully explore the potential of novel coformulations and combinations that build on the foundation of KEYTRUDA, with a goal to improve upon current standards of care and help even more patients with cancer,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “We are grateful to the patients and investigators for their participation and will leverage insights from this trial as we rapidly advance our diverse pipeline of novel mechanisms, including further study of this coformulation in lung cancer.”
Merck is committed to the development of new treatment options for patients with melanoma, including in earlier stages of disease, which build upon the current standard of care. The program includes the ongoing Phase 3 V940-001 study, in collaboration with Moderna, evaluating V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA as adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma.
In the U.S., KEYTRUDA has two approved indications in melanoma: for the treatment of patients with unresectable or metastatic melanoma, and for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
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 and pembrolizumab coformulation alone and in combination with other agents in over 3,000 patients.
Ongoing Phase 3 studies evaluating the vibostolimab and pembrolizumab coformulation in lung cancer, which are routinely monitored by external data monitoring committees, include KeyVibe-003, KeyVibe-006, KeyVibe-007 and KeyVibe-008. Interim external data monitoring committee safety reviews have not resulted in any safety-related study modifications to date. No changes to these studies are anticipated based on the KeyVibe-010 findings.
About KeyVibe-010
KeyVibe-010 is a randomized, double-blind, active comparator-controlled Phase 3 trial (ClinicalTrials.gov, NCT05665595) evaluating a coformulation of vibostolimab and pembrolizumab (MK-7684A) versus KEYTRUDA alone as adjuvant treatment for patients with resected high-risk Stage IIB-IV melanoma. The trial’s primary endpoint is RFS. Key secondary endpoints include distant metastasis-free survival (DMFS) and overall survival (OS). The study enrolled 1594 patients who were randomly assigned (1:1) to receive:
- Vibostolimab/pembrolizumab coformulation (pembrolizumab 200 mg/20 mL and vibostolimab 200 mg intravenously [IV] every 3 three weeks [Q3W] for up to 17 cycles); or
- Pembrolizumab (adult patients receive 200 mg and adolescent patients ≥40 kg receive 2 mg/kg [up to a maximum of 200 mg] IV Q3W for up to 17 cycles).
About melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with more than 330,000 new cases diagnosed worldwide in 2022. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be more than 100,000 new cases of melanoma diagnosed and more than 8,000 deaths resulting from the disease in the U.S. in 2024.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with more than 25 ongoing registrational studies across multiple types of cancer.
About vibostolimab
Vibostolimab (MK-7684) is an investigational humanized anti-TIGIT antibody discovered and developed by Merck. Vibostolimab 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. The coformulation of vibostolimab and pembrolizumab and is being evaluated in a wide range of cancers, including lung, other solid tumors and blood cancers.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
