Toripalimab trials in the country

Toripalimab (Toripalimab) is effective against melanoma. In POLARIS-01, toripalimab was administered at 3 mg/kg every two weeks until disease progression or unacceptable toxicity in 128 Chinese patients who had received prior systemic therapy. The achieved objective response rate (ORR) was 17.3%, and the disease control rate (DCR) was 57.5%. The disease control rate was defined as the percentage of patients achieving CR, PR or stable disease (SD) ; the median progression-free survival rate (PFS) and overall survival rate (OS) were 3.6 months and 22.2 months respectively. Toripalimab bred long-term survival benefits, the OS of PD-L1 positive patients was significantly longer than that of PD-L1 negative patients.

In another phase I study of 22 melanoma patients, the ORR, DCR, PFS and OS were 18.2%, 45.5%, 84 days and 448 days, respectively. In comparison, in KEYNOTE-151, pembrolizumab was administered to previously treated Chinese melanoma patients; the overall response rate was 16.7% and the DCR was 38.2%. The ORs for patients with acral melanoma, non-acral melanoma, and mucosal melanoma were 15.8%, 19.5%, and 13.3%, respectively, and the DCRs were 42.1% and 20.0%, respectively. Adjuvant toripalimab improves relapse-free survival in patients with mucosal melanoma, but its comparison with conventional chemotherapy remains to be performed.

The combination of toripalimab and the vascular endothelial growth factor inhibitor axitinib has shown efficacy in the treatment of mucosal melanoma. Vascular endothelial growth factor is an important growth factor for cancer growth and is upregulated in melanoma patients. Simultaneous blockade of PD-1 and vascular endothelial growth factor receptor 2 induces synergistic antitumor effects in mice inoculated with colon cancer cells. In the Phase Ib study, 33 Chinese patients received axitinib 5 mg twice daily and toripalimab 1 or 3 mg/kg every 2 weeks in dose escalation and cohort expansion phases until disease progression, unacceptable toxicity, or voluntary discontinuation was confirmed. The achieved ORR was 48.3%, the DCR was 86.2%, and the median PFS was 7.5 months. The combined program produced high response rates. The latest analysis of results showed that the median OS of these patients was 20.7 months. Later, the combination of toripalimab plus axitinib was tested in the adjuvant setting and resulted in pathological complete response (pCR), defined as the absence of viable tumor on all slides, in 14.3% of patients. In addition, the combination's effectiveness in advanced mucosal melanoma is currently being studied in a Phase II trial.

Toripalimab is also being tested in other settings to treat melanoma. For example, in patients with resectable stage IIIb-IVM1a acral melanoma, toripalimab plus granulocytes- Macrophage colony-stimulating factor OrienX010 achieved a pCR of 14.3%; intravenous administration of toripalimab plus intralesional injection OrienX010 achieved an ORR of 13.3% in liver metastases. Toripalimab combined with vorolanib achieved an ORR of 13.2% in advanced mucosal melanoma as first-line treatment.