Merck Discontinues Coformulation Arm of Phase III Trial Evaluating Vibostolimab/Keytruda Combo for Melanoma

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Merck is discontinuing the coformulation arm of the Phase III KeyVibe-010 trial (NCT05665595) analyzing the combination of vibostolimab (MK-7684) and Keytruda (pembrolizumab) in the adjuvant treatment of patients with resected high-risk melanoma (stage IIB-IV).¹ A pre-planned analysis conducted by an independent Data Monitoring Committee (DMC) found that the data met the pre-specified futility criteria for the trial’s primary endpoint of recurrence-free survival (RFS).

Patients in the vibostolimab and Keytruda cohort experienced a higher rate of discontinuation of all adjuvant treatment mainly due to immune-mediated adverse events (AEs) compared with patients in the Keytruda monotherapy cohort. Investigators deemed it highly unlikely that the combination therapy would be able to produce a statistically significant improvement in RFS.

“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 Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in a press release. “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.”¹

Vibostolimab, a novel humanized anti-TIGIT antibody, has been found to restore antitumor activity by preventing the TIGIT receptor from attaching to its ligands CD112 and CD155, which activates T lymphocytes that help eliminate tumor cells.²

Keytruda is an anti-PD-1 therapy that improves the immune system's ability to detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which leads to the activation of T lymphocytes that could affect the tumor and healthy cells.

To date, more than 1600 trials are evaluating Keytruda across a range of cancer types and treatment settings. Keytruda also has approved indications in melanoma; non-small cell lung cancer; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; gastric cancer; microsatellite instability-high or mismatch repair deficient cancer; microsatellite instability-high or mismatch repair deficient colorectal cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden-high cancer; cutaneous squamous cell carcinoma; and triple-negative breast cancer.

The randomized, double-blind, active comparator-controlled KeyVibe-010 trial compared the vibostolimab and pembrolizumab combination versus Keytruda monotherapy in the adjuvant treatment of patients with resected high-risk stage IIB-IV melanoma. In addition to the primary endpoint of RFS, key secondary endpoints included distant metastasis-free survival and overall survival.

Investigators randomly assigned 1594 patients to receive Keytruda at a dose of 200 mg/20 mL and vibostolimab 200 mg intravenously (IV) every three weeks for up to 17 cycles or Keytruda at a dose of 200 mg in adult patients and a dose of 2 mg/kg—up to a maximum of 200 mg—in adolescent patients ≥40 kg IV every three weeks for up to 17 cycles.

Merck stated that it will unblind the trial and is recommending patients in the vibostolimab and pembrolizumab cohort be presented with the option to switch to treatment with Keytruda monotherapy. They added that an evaluation of the study data is ongoing and will be shared with the scientific community and sent to regulatory agencies.

The vibostolimab and pembrolizumab combination is under evaluation across various cancer types, including lung cancer, other solid tumors, and blood cancers. Additional ongoing Phase III trials analyzing the combination in lung cancer include KeyVibe-003, KeyVibe-006, KeyVibe-007, and KeyVibe-008.

References

1. Merck Provides Update on Phase 3 KeyVibe-010 Trial Evaluating an Investigational Coformulation of Vibostolimab and Pembrolizumab as Adjuvant Treatment for Patients With Resected High-Risk Melanoma. News release. Merck. May 13, 2024. Accessed May 13, 2024. https://www.merck.com/news/merck-provides-update-on-phase-3-keyvibe-010-trial-evaluating-an-investigational-coformulation-of-vibostolimab-and-pembrolizumab-as-adjuvant-treatment-for-patients-with-resected-high-risk-melanoma/

2. 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 May 13, 2024. https://www.merck.com/news/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/