according to a presentation made as part of the American Society of Clinical Oncology virtual scientific program.
The combination was well tolerated and “the preliminary efficacy seems to be promising,” which warrants a phase 3 trial, said investigator Jun Guo, MD, of the Peking University Cancer Hospital and Institute in Beijing, who presented the findings.
Mucosal melanoma does not respond as well as cutaneous melanoma to standard programmed death-1 (PD-1) blockade, so investigators are looking for additional options, Dr. Guo noted. Earlier studies have shown that vascular endothelial growth factor expression correlates negatively with clinical outcome, so the combination of VEGF inhibition with PD-1 blockade might provide therapeutic opportunities.
To find out, Dr. Guo and colleagues tested the anti-PD-1 antibody toripalimab in combination with the VEGF inhibitor axitinib in a phase 1 trial. The trial was conducted in China, where mucosal melanoma accounts for up to a quarter of all melanoma cases and where toripalimab is approved to treat mucosal melanoma.
The trial enrolled 33 patients with pathologically confirmed metastatic mucosal melanoma. The esophagus and genital tract were the most common primary lesion sites (both 21.2%). The patients’ average age was 53.4 years, and 60.6% were women. Two patients (6.1%) had previously received systemic chemotherapy. Most (64.6%) were PD–ligand 1 (PD-L1) negative, and most (60.6%) were BRAF/RAS/NF1 wild type.
The patients received axitinib at 5 mg twice daily plus toripalimab at 3 mg/kg every 2 weeks until confirmed disease progression, unacceptable toxicity, or voluntary withdrawal.
As of May 2, 2020, the overall response rate was 48.5%. There were 15 partial responses and 1 complete response. The median duration of response was 13.7 months. The median progression-free survival was 7.5 months, and the median overall survival was 20.7 months.
Progression-free and overall survival were numerically higher in PD-L1-positive subjects and those with higher tumor mutation burdens. An expression profile of 12 genes related to inflammation and angiogenesis showed a significant correlation with response. This might help identify patients most likely to respond to the combination, but further validation is needed, Dr. Guo said.
A total of 32 subjects (97%) have had a treatment-related adverse event, including 13 (39.4%) with grade 3-5 events. The most common of these were proteinuria, hypertension, and neutropenia (all 9.1%).
“So does this study address the unmet need? In many ways, yes,” said Ryan Sullivan, MD, an assistant professor of hematology/oncology at Massachusetts General Hospital in Boston, and the discussant on Dr. Guo’s presentation.
“However, the data to date [don’t] mean we should be treating all of our mucosal melanoma patients with axitinib plus an anti-PD-1 antibody. There needs to be randomized data, but I would describe this data as very encouraging,” he said.
The study was funded by the maker of toripalimab, Shanghai Junshi Bioscience. Dr. Guo disclosed relationships with Shanghai Junshi Bioscience and Pfizer, maker of axitinib. Other investigators are employed by Shanghai Junshi Bioscience. Dr. Sullivan reported institutional research funding from Pfizer.
SOURCE: Guo J et al. ASCO 2020, Abstract 10007.