Background: Pembrolizumab is an anti−PD-1 monoclonal antibody that has been shown to significantly improve recurrence-free survival and distant metastasis-free survival when used as adjuvant therapy in patients with high-risk resected melanoma (Long GV, et al. Lancet Oncol. 2022;23:1378-88; Eggermont AMM, et al. Lancet Oncol. 2021;22:643-54). Combining pembrolizumab with other therapies may further improve outcomes in this setting. Vibostolimab is an anti-TIGIT monoclonal antibody that showed antitumor activity and manageable safety when used in combination with pembrolizumab in patients with advanced solid tumors in the phase 1 KEYVIBE-001 study (Niu J, et al. Ann Oncol. 2022;33:169-80). The randomized, double-blind, phase 3 KEYVIBE-010 study (NCT05665595) is designed to evaluate the efficacy and safety of adjuvant coformulated vibostolimab and pembrolizumab (MK-7684A) versus pembrolizumab alone in patients with resected high-risk stage IIB-IV melanoma. Methods: Eligible patients are ≥12 years of age (weighing ≥40 kg if < 18 years), with surgically resected stage IIB or IIC (pathologic or clinical), III, or IV cutaneous melanoma per AJCC 8th edition guidelines, and an Eastern Cooperative Oncology Group performance status of 0 or 1 (Lansky play-performance scale ≥70 if < 16 years; Karnofsky performance status ≥70 if ≥16 to < 18 years). Patients must not have received any prior systemic therapy beyond complete resection and no more than 12 weeks can have elapsed between final surgical resection and randomization. Patients with ocular, mucosal, or conjunctival melanoma, and prior allogeneic tissue/solid organ transplant are excluded. Patients will be stratified by risk. Approximately 1560 patients will be randomly assigned 1:1 to receive intravenous coformulated vibostolimab 200 mg with pembrolizumab 200 mg or pembrolizumab 200 mg (2 mg/kg up to a maximum of 200 mg for adolescents) every 3 weeks. Treatment will continue for 17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal. The primary end point is recurrence-free survival by investigator review. Secondary end points are distant metastasis-free survival by investigator review, overall survival, safety and tolerability, and quality of life. Hazard ratios and 95% confidence intervals will be estimated using a stratified Cox regression model with the Efron method of handling ties, with treatment as a covariate. Between-treatment differences will be evaluated using a stratified log-rank test. Enrollment is ongoing. Clinical trial information: NCT05665595.