Harbour BioMed (HBM; HKG: 2142), a biotech operating out of the United States, the Netherlands, and Suzhou (China), announced the conclusion of a Phase I clinical study for its anti-CTLA-4 antibody HBM4003 combined with Junshi Bio’s programmed death-1 (PD-1) inhibitor Tuoyi (toripalimab) in advanced melanoma. The study has shown that HBM4003 0.3 mg/kg combined with Tuoyi 240 mg Q3W shows good anti-tumor activity in patients with advanced melanoma, including acrosomal and mucosal subtypes, and also shows acceptable safety. Data has been published at the European Society for Medical Oncology 2022 annual meeting.
Study Design and Results
The open-label Phase I study is designed to assess the safety, tolerance, pharmacokinetics (PK)/pharmacodynamics (PD), and preliminary efficacy of the combo in advanced melanoma and other solid tumors. In the dose ascending part, patients with solid tumors received three dose levels of HBM4003 (0.03 mg/kg, 0.1 mg/kg and 0.3 mg/kg) in combination with 240 mg of Tuoyi once every three weeks (Q3W). In the dose expansion part, patients with advanced melanoma (n=26) received HBM4003 0.3 mg/kg combined with 240 mg of Tuoyi Q3W at the phase II recommended dose (RP2D).
As of August 31, 2022, 40 patients had received drug treatment, with a median follow-up time of 106.5 days. HBM4003 combined with Tuoyi in advanced melanoma showed good safety. A total of 87.5% (35/40) of patients reported treatment-related adverse events (TRAE), and 20% (8/40) patients reported ≥ grade 3 TRAE. Most of the reported TRAEs were skin rashes (30.0%). The combo showed strong anti-tumor activity, regardless of whether the patients received front-line treatment. The overall response rate (ORR) and disease control rate (DCR) of the anti PD-(L)1 naïve treatment group were 53.3% and 73.3% respectively. The ORR and DCR of anti PD-(L)1 treated group were 11.8% and 35.3% respectively.
HBM4003: Mechanism and Development
HBM4003 is HBM’s first fully human mAb generated using their proprietary heavy chain antibody mouse platform. Described as a next-generation checkpoint inhibitor, the drug candidate is designed to inhibit CTLA-4 in order to enhance T cell activity and improve the anti-tumor response. Harbour has initiated multiple clinical studies for the antibody in melanoma, non-small cell lung cancer, hepatocellular carcinoma, neuroendocrine tumors, and others.
Toripalimab: Regulatory Milestones
Toripalimab was China’s first domestic PD-1 inhibitor to be approved (in December 2018) as a second-line treatment for melanoma. Further indication nods were granted in February 2021 as a second-line treatment of nasopharyngeal carcinoma (NPC), in April 2021 for locally advanced or metastatic urothelial cancer (UC) in previously treated patients, in November 2021 as a first-line treatment for NPC, in May 2022 as a first-line treatment for esophageal squamous cell carcinoma (ESCC), and in September 2022 as first-line treatment for EGFR negative, ALK negative non-small cell lung cancer (NSCLC). The molecule was included on the National Reimbursement Drug List (NRDL) for three indications last year, the only PD-1 inhibitor to treat melanoma and NPC on the list.-Fineline Info & Tech
