HUTCHMED (China) Limited announced that it has initiated a Phase I trial in China of HMPL-653, an investigational novel, highly selective, and potent colony-stimulating factor 1 receptor (“CSF-1R”) inhibitor. The first patient received their first dose on January 18, 2022. The Phase I trial is a multicenter, open-label, single-arm study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of HMPL-653 in the treatment of patients with advanced or metastatic solid tumors and tenosynovial giant cell tumors (“TGCT”).

Approximately 110 patients are expected to be enrolled in the dose escalation and expansion phase of this study. The primary endpoints are dose limiting toxicity, safety, tolerability, recommended phase II dose and maximum tolerated dose. The secondary endpoints include pharmacokinetics, objective response rate, progression free survival, disease control rate, and overall survival.

The lead principal investigator is Dr. Cheng Ying of the Jilin Cancer Hospital, which is the lead institution for this study. HMPL-653 is an investigational novel, highly selective, and potent CSF-1R inhibitor designed to target malignant driven tumors as a monotherapy or in combination with other drugs. CSF-1R is usually expressed on the surface of macrophages and can promote growth and differentiation of macrophages after binding with its ligand, CSF-1. A number of studies have shown that blocking the CSF-1R signaling pathway could effectively modulate the tumor microenvironment, relieve tumor immunosuppression, and synergize with other anti-cancer therapies such as immune checkpoint inhibitors to achieve tumor inhibition.

It has been demonstrated in several clinical studies that other CSF-1R inhibitors, by inhibiting CSF-1R activity, could be used to treat TGCT, and to treat a variety of malignancies through combination with immuno-oncology and/or other therapeutic agents. Currently no CSF-1R inhibitor has been approved in China.