The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression free survival of 7.5 months in a phase 1b trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial.This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg Q2W plus axitinib 5 mg BID for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2±1week after surgery for 44 weeks. The primary end point is the pathologic response rate according to International Neoadjuvant Melanoma Consortium recommendations.Between Aug 2019 and Oct 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. Median follow-up time was 34.2 months (95% CI [20.4 to 48.0]). The pathologic response rate was 33.3% (8/24, 4 pCR, 4pPR). Median event free survival for all patients was 11.1 months (95% CI [5.3, 16.9]). Median OS was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment related AEs and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 non-responders). Multiplex IHC demonstrated a significant increase of CD3+ (p=0.0032) and CD3+CD8+ (p=0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders.Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.NCT04180995.Copyright © 2023. Published by Elsevier Ltd.