Overall survival and biomarker analysis of a phase Ib combination study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) with axitinib in patients with metastatic mucosal melanoma.

10007 Background: Metastatic mucosal melanoma responds poorly to PD-1 blockade therapy in comparison with cutaneous melanoma. Vascular endothelial growth factor (VEGF) is indicated to play an important immunosuppressive role in mucosal melanoma. Combination of VEGF inhibition with PD-1 blockade might provide therapeutic opportunities. Toripalimab was approved as a second-line treatment for metastasis melanoma in Dec 2018. This study is to evaluate the safety and clinical efficacy of toripalimab combined with axitinib for the treatment of metastatic mucosal melanoma. (Clinical trial ID: NCT03086174). Methods: Patients with metastatic melanoma receive 1 or 3 mg/kg toripalimab Q2W in combination with 5 mg axitinib BID until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and gene expression profile (GEP) will be evaluated for correlation with clinical response. Results: From April 2017 to April 2018, 33 patients were enrolled in the study. No DLT or treatment related death was observed. 97% patients experienced treatment related AE (TRAE) and 39.4% patients experienced Grade 3-4 TRAEs. Most common TRAEs include diarrhea, proteinuria, hand and foot syndrome and hypothyroidism. Only one patient discontinued treatment due to TRAE. Among 29 treatment naïve mucosal melanoma patients, 14 PR and 11 SD were observed for an ORR of 48.3% and a DCR of 86.2%. The median DOR was 13.7 months. The median PFS was 7.5 months and the median OS was 20.7 months. PD-L1 expression or TMB had no significant differences in responders versus non-responders. In contrast, GEP scores of eight selected immune-related and four angiogenesis-related genes showed strong correlation with clinical response, whereas previous published immune related signature or angiogenesis signature alone had no correlation. Conclusions: Toripalimab combined with axitinib is a promising treatment option for metastatic mucosal melanoma. GEP scores of selected immune-related and angiogenesis-related genes might predict the response to the combination. A randomized 3-arm Phase 2 trial has been initiated to compare toripalimab plus axitinib with toripalimab or axitinib alone. Clinical trial information: NCT03086174.