Merck Discontinues KeyVibe-010 Trial of Vibostolimab/Pembrolizumab in Resected High-Risk Melanoma

The phase 3 KeyVibe-010 trial (NCT05665595) evaluating the combination of adjuvant vibostolimab (MK-7684A) and pembrolizumab (Keytruda) vs pembrolizumab alone in patients with resected high-risk stage IIB, IIC, III, and IV melanoma has been discontinued.¹

During a preplanned analysis of the anti-TIGIT antibody and anti–PD-1 combination, data showed that the primary end point of recurrence-free survival (RFS) met the prespecified futility criteria in the randomized, double-blind trial. However, the high rate of discontinuation of all adjuvant therapy by patients in the investigational arm compared with the pembrolizumab-only arm made it highly unlikely that the trial would achieve a statistically significant improvement in RFS for patients.

These discontinuations in the combination arm were due to immune-mediated adverse effects, and an independent data monitoring committee recommended that Merck unblind the study. Following this recommendation, Merck will be unblinding the study treatment arms and recommending that patients who were receiving the vibostolimab and pembrolizumab combination be offered the option to be treated with pembrolizumab monotherapy.

“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 [pembrolizumab], with a goal to improve upon current standards of care and help even more patients with cancer,” Marjorie Green, MD, senior vice president and head of late-stage oncology and global development at Merck Research Laboratories, said in the 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.”

Melanoma is the most serious type of skin cancer and involves abnormal growth of pigment-producing cells. The incidence of melanoma has been increasing globally and in the United States, and this disease represents a significant portion of skin cancer fatalities, creating an unmet treatment need.

In the active comparator–controlled KeyVibe-010 trial, investigators evaluated the combination of vibostolimab and pembrolizumab vs pembrolizumab monotherapy in the adjuvant treatment setting for patients with resected, high-risk Stage IIB to IV melanoma.

Vibostolimab is an experimental anti-TIGIT antibody designed to enhance the body’s antitumor response by preventing the TIGIT receptor from binding to the CD112 and CD155 ligands, which activates T lymphocytes to target and destroy tumor cells. Pembrolizumab is an anti–PD-1 therapy that boosts the immune system’s ability to detect and combat tumor cells by blocking the PD-1 interaction with the PD-L1 and PD-L2 ligands, thereby activating T lymphocytes against cancerous and healthy cells. Merck is investigating the combination of vibostolimab and pembrolizumab in various cancers, including lung cancer; solid tumors, such as melanoma; and blood cancers.

The primary end point of KeyVibe-010 was RFS, and key secondary end points included distant metastasis-free survival and overall survival. A total of 1594 patients were randomly assigned 1:1 to receive treatment consisting of intravenous (IV) vibostolimab at 200 mg plus pembrolizumab at 200 mg/20 mL every 3 weeks for up to 17 cycles; or IV pembrolizumab at 200 mg (adolescent patients received up to a maximum of 200 mg) every 3 weeks for up to 17 cycles.

Ongoing phase 3 trials continue to assess the combination of vibostolimab and pembrolizumab in other indications, such as lung cancer, with independent data monitoring committees overseeing this process. Safety reviews conducted by these committees have not yet prompted study modifications due to safety, and based these KeyVibe-010 data, no alterations to any additional ongoing studies of the combination are anticipated.

Results from ongoing data analyses of this study will be shared with the scientific community and will subsequently be communicated to regulatory agencies.

Reference

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/