Chinese commercial-stage biopharmaceutical company HUTCHMED has commenced a Phase I trial of its investigational oral drug, HMPL‑295, for the treatment of advanced malignant solid tumour patients.

The first subject in the Phase I trial was dosed on 2 July 2021.

A selective oral inhibitor of the extracellular signal-regulated kinase (ERK), HMPL‑295 is a downstream factor of the RAS-mitogen activated protein kinase (RAS-MAPK) pathway signalling cascade.

In certain diseases, especially cancer, the RAS-MAPK pathway is dysregulated and mutations or non-genetic events cause hyperactivation of the pathway in more than 50% of cancers.

HMPL-295 could potentially address intrinsic or acquired resistance from upstream mechanisms, including RAS, RAF and MEK.

The multi-centre, open-label Phase I trial will assess the safety, tolerability, pharmacokinetics and initial efficacy profile of HMPL-295.

It will enrol a total of 52 to 87 subjects, including 30 to 60 patients for dose escalation.

HUTCHMED noted that the number of subjects to be screened in the trial will be based on the number of dose levels analysed, the incidence of dose-limiting toxicity (DLT) in each dose group and the failure rate of screening.

This trial will also aid in detecting the maximum tolerated dose and selecting recommended Phase II dose (RP2D) in advanced malignant solid tumour patients.

Following the initial dose-escalation stage, another ten to 15 participants will be recruited at the RP2D to further study HMPL-295’s safety and preliminary efficacy.

Furthermore, the company intends to conduct an exploratory study on the pharmacokinetic biomarkers of the therapy.

HUTCHMED focuses on developing and marketing targeted medicines and immunotherapies for cancer and immunological diseases.

With more than 1,300 employees, the company has advanced ten oncology drug candidates from in-house discovery into the clinic. Three of these cancer drugs have received approval.