Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB–IV melanoma (KEYVIBE-010): a randomised, double-blind, phase 3 study

BACKGROUND: Combination therapy with vibostolimab plus pembrolizumab has previously shown promising antitumor activity in melanoma. We aimed to evaluate the efficacy and safety of vibostolimab coformulated with pembrolizumab as adjuvant therapy for high-risk resected melanoma. METHODS: This randomised, double-blind, phase 3 study was done at 205 global sites (hospitals and cancer centres). Participants aged 12 years or older with surgically resected, stage IIB-IV cutaneous melanoma per the American Joint Committee on Cancer Cancer Staging Manual 2017 (8th edition), with no evidence of metastatic disease after resection, were randomly assigned (1:1) to receive vibostolimab 200 mg coformulated with pembrolizumab 200 mg or pembrolizumab 200 mg alone intravenously every 3 weeks. Randomisation was done using an interactive response technology system and was stratified by risk-based staging and geographical region. Participants, investigators, and site staff were masked to group assignment. The primary endpoint was recurrence-free survival assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the study treatment. The protocol-prespecified first interim analysis was an event-driven nonbinding futility analysis of recurrence-free survival that was planned for when 111 events had occurred (futility bar of observed HR 0·95). This study is registered with ClinicalTrials.gov (NCT05665595), and is closed to recruitment. FINDINGS: Between Jan 19, 2023, and March 6, 2024, 1402 participants were randomly assigned to receive coformulated vibostolimab-pembrolizumab (n=701) or pembrolizumab (n=701). At the first interim analysis, median study follow-up, defined as time from randomisation to data cutoff, was 4·2 months (IQR 1·9-6·7). The median age was 61·0 years (IQR 51·0-70·0), 829 (59%) of 1402 participants were male and 573 (41%) were female. 1107 (79%) of participants were White, 273 (19%) were Asian, and 22 (2%) were of other race or race was missing. At the time of the first interim analysis, a total of 119 (8%) of 1402 participants had had a recurrence-free survival event, including 67 (10%) of 701 in the vibostolimab-pembrolizumab group and 52 (7%) of 701 in the pembrolizumab alone group. The median recurrence-free survival was not reached in either group; the hazard ratio for recurrence-free survival in the vibostolimab-pembrolizumab group versus pembrolizumab alone group was 1·25 (95% CI 0·9-1·8). The most common (occurred in more than five participants) grade 3 or higher treatment-related adverse events were adrenal insufficiency in 13 (2%) participants, hepatitis in 11 (2%) participants, rash in 9 (1%) participants, maculopapular rash in 7 (1%) participants, and pruritus in 6 (1%) participants in the vibostolimab-pembrolizumab group and increased alanine aminotransferase in 7 (1%) participants in the pembrolizumab alone group. Treatment-related serious adverse events occurred in 74 (11%) participants and 30 (4%) participants, respectively. Treatment-related adverse events led to death in two (<1%) participants in the vibostolimab-pembrolizumab group (myasthenia gravis and myocarditis) and one participant (<1%) in the pembrolizumab group (myositis). The external data monitoring committee decided to discontinue the study according to prespecified futility criteria. INTERPRETATION: Vibostolimab coformulated with pembrolizumab did not provide additional clinical benefit versus pembrolizumab as adjuvant therapy in participants with resected stage IIB-IV melanoma. Pembrolizumab monotherapy remains a standard of care for resected high-risk melanoma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.