A First-in-Human Study of ATM Inhibitor Lartesertib as Monotherapy in Patients with Advanced Solid Tumors.

ABSTRACT:

Purpose

This first-in-human phase I, open-label study (NCT04882917) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and maximum tolerated dose (MTD) of the highly potent and selective oral ataxia-telangiectasia-mutated kinase inhibitor lartesertib.

Patients and methods

Patients with advanced solid tumors received oral doses of lartesertib for a dose range of 100 to 400 mg once daily. Dose escalation was based on PK, PD, and safety data guided by a Bayesian two-parameter logistic regression model. Molecular responses were assessed in ctDNA samples.

Results

Twenty-two patients received lartesertib at doses of 100 mg (n = 2), 200 mg (n = 7), 300 mg (n = 9), and 400 mg (n = 4) once daily. Maculopapular rash was the most common dose-limiti

SUBMITTER: Siu LL 

PROVIDER: S-EPMC12580772 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature