FDA ‘Fast Tracks’ Toripalimab in Frontline Mucosal Melanoma

The FDA granted a Fast Track designation to the humanized PD-1 monoclonal antibody toripalimab for the first-line treatment of patients with mucosal melanoma.

The FDA granted a Fast Track designation (FTD) to the humanized PD-1 monoclonal antibody toripalimab for the first-line treatment of patients with mucosal melanoma, announced Junshi Biosciences, in a press release.1

The agent, which is manufactured in China, has already received a Breakthrough Therapy designation from the FDA as a treatment for recurrent/metastatic nasopharyngeal carcinoma. Receipt of an FTD designation from the FDA will advance the development of toripalimab in the mucosal melanoma setting. The FDA also granted an Investigational New Drug Application to support a phase 3 study of toripalimab plus axitinib (Inlyta), a small molecule tyrosine kinase inhibitor, versus pembrolizumab (Keytruda) as treatment of patients with unresectable, locally advanced, or metastatic disease.

The total target study enrollment is 220 patients who will be randomized in a 1:1 ratio into 2 treatment arms. Progression-free survival (PFS) will be the primary end point of the study. Patients enrolled will also be evaluated for objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety.

Previously, the combination of toripalimab and axitinib showed promise in the mucosal melanoma patient population, according to results from a phase 1b study (NCT03086174) published in the Journal of Clinical Oncology.2

The cohort included 30 patients with mucosal melanoma who were administered toripalimab at 1 or 3 mg/kg via intravenous infusion biweekly along with axitinib 5 mg given orally twice a day. The study was a single-center, dose-escalation, and cohort-expansion evaluation. The primary end point explored treatment-related adverse events (TRAEs). The secondary end points were ORR, DOR, disease control rate (DCR), time to response, PFS, and OS.

The safety analysis showed that the combination was tolerable overall and showed no dose-limiting toxicities in the dose-finding phase of the study, which included 6 patients. In a safety analysis of the full cohort, 97% of patients experienced TRAEs. The toxicities observed were predominantly graded 1 or 2 in severity. None of the grade 1/2 events led to death.

Grade 3 or higher TRAEs were observed in 39.4% of the study population, which included 1 case of grade 4 lipase elevation. The grade 3 events observed in 13 patients total were proteinuria (n = 3), hypertension (n = 3), neutropenia (n = 3), alanine aminotransferase elevation (n = 2), weight loss (n = 2), diarrhea, creatine kinase elevation, aspartate aminotransferase elevation (n = 1 each ), lipase elevation (n = 1), leukopenia (n = 1), anemia (n = 1), γ-glutamyl transferase elevation (n = 1), blood creatinine elevation (n = 1), hyponatremia (n = 1), and esophageal fistula (n = 1).

Some patients in the study also experienced immune-related AEs (IRAEs). The most common IRAEs observed were diarrhea (60.6%), hypothyroidism (51.5%), and alanine aminotransferase elevation (42.4%).

In terms of efficacy, the study revealed that toripalimab plus axitinib demonstrated promising antitumor activity with an ORR of 48.3% and DCR of 86.2%. In addition, the combination led to a median PFS of 7.5 months.’

The phase 1b patient population was comprised of individuals with ECOG performance scores of 0 or 1 who had disease progression or developed intolerance during frontline therapy. Patients were required to have measurable disease, a minimum life expectancy of 3 months, and adequate laboratory values at baseline screening.

Orphan Drug Designation was granted to toripalimab/axitinib by the FDA shortly after data were reported from the phase 1b study of patients with mucosal melanoma.


1. FDA grants toripalimab Fast Track designation for mucosal melanoma. News release. Junshi Biosciences. January 25, 2021. Accessed January 25, 2021.

2. Sheng X, Yan X, Chi Z, et al. Axitinib in combination with toripalimab, a humanized immunoglobulin g4 monoclonal antibody against programmed cell death-1, in patients with metastatic mucosal melanoma: an open-label phase ib trial. J Clin Oncol. 2019;37(32):2987-2999. doi:10.1200/JCO.19.00210

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