Combination toripalimab and axitinib may have better antitumor activity than either drug alone in patients with treatment-naive unresectable or metastatic mucosal melanoma, according to interim results of a trial presented at the 2022 ASCO Annual Meeting.

The randomized, controlled phase 2 trial ( Identifier: NCT03941795) compared efficacy and safety of combination toripalimab (an antibody to programmed death 1) and axitinib (an inhibitor of the vascular endothelial growth factor receptor) against those of monotherapy with each drug individually.

All patients had pathologically confirmed, treatment-naive unresectable or metastatic mucosal melanoma. They were stratified by programmed death ligand 1 status and randomly and evenly assigned to 3 treatment groups: combination therapy (toripalimab 240 mg every 3 weeks plus axitinib 5 mg twice a day); toripalimab monotherapy (toripalimab 240 mg every 3 weeks); and axitinib monotherapy (axitinib 5 mg twice a day). Patients in the monotherapy arms who met certain criteria after disease progression could cross over to receive the combination.

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The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, duration of response, overall survival, and safety.

A total of 51 patients (58.8% female) were randomly assigned to treatment: 18 to combination therapy, 20 to toripalimab monotherapy, and 13 to axitinib monotherapy. The disease anatomic site was head and neck in 49.0% of patients, gastrointestinal in 29.4%, and gynecologic in 21.6%. At study entry, 3.9% of patients had stage II or III unresectable disease, while 23.5% had stage M1a, 17.6% had stage M1b, and 51.0% had stage M1c.

At a median follow-up of 6.6 months, results reported in a poster session showed that the median progression-free survival was 5.8 months with combination toripalimab-axitinib, 2.8 months with toripalimab alone, and 1.4 months with axitinib alone (P =.170 across arms). With axitinib monotherapy as the comparator, there were trends toward a lower risk of progression-free survival events with combination therapy (hazard ratio, 0.44; 95% CI, 0.18-1.08; P =.064) and with toripalimab monotherapy (hazard ratio, 0.54; 95% CI, 0.24-1.22; P =.905).

Patients in the combination arm had a confirmed objective response rate of 35.3% (29.7% when cross-over patients were included) compared with 17.6% and 0% in the toripalimab and axitinib monotherapy arms, respectively. The disease control rate for the combination was 82.4% (70.3% when cross-over patients were included) vs 52.9% and 58.3% with the respective single drugs alone.

Most patients (98%) had a treatment-emergent adverse event (TEAE). Grade 3 and higher TEAEs occurred in 27.8% of the combination arm, 15.0% of the toripalimab arm, and 46.2% of the axitinib arm 3. Serious AEs occurred in 2 patients, 0 patients, and 1 patient, respectively. The most frequently occurring TEAEs were mild (grades 1 and 2) and included increased thyroid-stimulating hormone level, elevated triglyceride level, proteinuria, increased transaminase level, leukopenia, and elevated bilirubin level.

“Toripalimab combined with axitinib showed a manageable safety profile with no new safety signal observed,” the researchers stated.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Cui C, Lian B, Sheng X, et al. Toripalimab plus axitinib versus toripalimab or axitinib alone in patients with treatment-naive unresectable or metastatic mucosal melanoma: Interim results from a randomized, controlled, phase II trial. Presented at ASCO 2022; June 3-7, 2022. Abstract 9512.