First-in-Human Phase I Study of MP0250, a First-in-Class DARPin Drug Candidate Targeting VEGF and HGF, in Patients...

Area of Science:

• Oncology
• Pharmacology
• Drug Development

Background:

• MP0250 is a first-in-class DARPin drug candidate designed to inhibit both vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF).
• These targets are crucial in disrupting the tumor microenvironment, suggesting potential anticancer activity.

Purpose of the Study:

• To evaluate the safety, tolerability, and pharmacokinetics of MP0250 in patients with advanced solid tumors.
• To determine the maximum tolerated dose (MTD) of MP0250.

Main Methods:

• A multicenter, open-label, repeated-dose, phase I study involving 45 patients with advanced solid tumors.
• Dose-escalation and dose-confirmation cohorts were used, with MP0250 administered intravenously every 2 or 3 weeks.

Main Results:

• The MTD was determined to be 8 mg/kg every 2 weeks or 12 mg/kg every 3 weeks.
• Common adverse events included hypertension, proteinuria, diarrhea, and nausea, consistent with VEGF and HGF inhibition.
• Signs of antitumor activity were observed, including stable disease in 24 patients and one unconfirmed partial response.

Conclusions:

• MP0250 demonstrated suitable tolerability and appropriate pharmacokinetic properties in this first-in-human study.
• The drug candidate shows potential for further development, particularly in combination with other anticancer therapies.