Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors.

ABSTRACT:

Background

Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.

Methods

This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50-300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic regression model with overdose control.

Results

Doses

SUBMITTER: Waqar SN 

PROVIDER: S-EPMC9098584 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature