Neoadjuvant Toripalimab Plus Axitinib Demonstrates Promising Response Among Patients With Resectable Mucosal Melanoma

According to results from a phase 2 trial, neoadjuvant administration of toripalimab, a humanized anti-PD1 IgG4 monoclonal antibody, plus axitinib resulted in promising pathologic response rates among patients with resectable, metastatic mucosal melanoma.

“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,” stated Bin Lian, MD, Peking University Cancer Hospital and Institute, Beijing, China, and coauthors. “Despite these promising results, the use of this combination in a neoadjuvant setting remains unknown.”

In this single-arm, open-label study, 29 patients with resectable, metastatic mucosal melanoma received 3 mg/kg of toripalimab once every 2 weeks plus 5 mg of axitinib twice daily for 8 weeks as neoadjuvant therapy followed by surgical resection. After an average of 2 weeks post-surgery, patients continued with 3 mg/kg of toripalimab once every 2 weeks for a duration of 44 weeks. The primary end point was pathologic response rate according to International Neoadjuvant Melanoma Consortium recommendations. Secondary end points included median event-free survival (EFS), median overall survival (OS), safety, and tumor tissue biomarkers. 

At a median follow-up of 34.2 months, 24 patients underwent surgical resection and pathological response rate was 33.3%. Median EFS was 11.1 months and median OS was not achieved. Grade 3/4 treatment-related adverse events occurred in 8 patients with no treatment-related deaths reported. Multiplex IHC of tissue samples from 5 respondents and 12 non-respondents collected at baseline and after resection identified pathological responders experienced a significant increase of CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy. 

Dr Lian and coauthors concluded, “Our study suggests that toripalimab plus axitinib may provide a promising new neoadjuvant treatment approach for patients with resectable mucosal melanoma.” 

Source: 

Lian B, Li Z, Wu N, et al. Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma. Ann Oncol. Published online: November 11, 2023. doi: 10.1016/j.annonc.2023.10.793