Multicenter phase 1 study of toripalimab plus the anti-CTLA-4 antibody HBM4003 for advanced melanoma and other solid tumors

HBM4003 is a novel anti-CTLA-4 heavy chain-only antibody. A multicenter phase 1 trial in China evaluated the combination of HBM4003 plus toripalimab (anti-PD-1) in patients with advanced melanoma and other solid tumors. The recommended phase 2 dose (RP2D) was toripalimab 240 mg plus HBM4003 0.3 mg/kg every three weeks. Ninety percent of patients experienced at least one treatment-related adverse event (grade ≥ 3 in 25%) en 12.5% experienced immune-related adverse events. Among 32 advanced melanoma patients receiving the RP2D, the objective response rate was 33.3% in the anti-PD-(L)1 naïve subgroup and 5.9% in the anti-PD-(L)1 pretreated subgroup. Among patients with advanced mucosal melanoma, the ORR was 40.0% in the anti-PD-(L)1 naïve subgroup and 10.0% in the anti-PD-(L)1 pretreated subgroup. The authors conclude that the combination of toripalimab and HBM4003 demonstrated manageable safety in solid tumors with promising antitumor activity, especially in PD-1 treatment-naïve mucosal melanoma.