In an interim analysis of a phase III trial (KEYVIBE-010) reported in The Lancet Oncology, Dummer et al found that adjuvant therapy with a coformulation of the anti-TIGIT antibody vibostolimab with pembrolizumab did not improve outcomes vs pembrolizumab alone in patients with resected high-risk stage IIB to IV melanoma.
Study Details
In the global double-blind trial, 1,402 patients aged 12 years or older were randomly assigned between January 2023 and March 2024 to receive vibostolimab at 200 mg coformulated with pembrolizumab at 200 mg (n = 701) or pembrolizumab alone at 200 mg every 3 weeks (n = 701). Treatment continued for up to 17 cycles or until disease recurrence, disease progression, or unacceptable toxicity. The primary endpoint was recurrence-free survival. The prespecified first interim analysis was an event-driven nonbinding futility analysis of recurrence-free survival planned at occurrence of 111 events, with a futility bar of an observed hazard ratio of 0.95.
Key Findings
At first interim analysis, median follow-up was 4.2 months (interquartile range = 1.9–6.7 months). A total of 119 (8%) of 1,402 patients had had a recurrence-free survival event, including 67 patients (10%) in the vibostolimab plus pembrolizumab group and 52 (7%) in the pembrolizumab group; the hazard ratio for recurrence-free survival for the vibostolimab plus pembrolizumab group vs the pembrolizumab group was 1.25 (95% confidence interval [CI] = 0.9–1.8). Rates at 6 months were 80% vs 85%. The external data monitoring committee decided to discontinue the study according to prespecified futility criteria.
Grade ≥ 3 treatment-related adverse events occurred in 16% of the vibostolimab plus pembrolizumab group (most commonly adrenal insufficiency and hepatitis, in 2% each) and in 7% of the pembrolizumab group (no specific event in more than 1% of patients). Treatment-related serious adverse events occurred in 11% vs 4% of patients, and treatment-related adverse events led to discontinuation of treatment in 12% vs 6%. Treatment-related death occurred in two patients in the vibostolimab plus pembrolizumab group (due to myasthenia gravis and myocarditis) and in one patient in the pembrolizumab group (due to myositis).
The investigators concluded: “Vibostolimab coformulated with pembrolizumab did not provide additional clinical benefit vs pembrolizumab as adjuvant therapy in participants with resected stage IIB–IV melanoma. Pembrolizumab monotherapy remains a standard of care for resected high-risk melanoma.”
Reinhard Dummer, MD, of the Department of Dermatology, University Hospital Zürich, Zürich, Switzerland, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit thelancet.com.
