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Debio 0123, a WEE1 kinase inhibitor: Phase 1 results from dose escalation in patients with advanced solid tumors

Kyriakos P Papadopoulos1, Manish R Sharma2, Reinhard Dummer3

  • 1START Center for Cancer Research, San Antonio, TX, USA.

European Journal of Cancer (Oxford, England : 1990)
|May 22, 2026
PubMed
Abstract

Insights

The WEE1 inhibitor Debio 0123 showed a manageable safety profile in patients with advanced solid tumors. Further investigation is supported by observed antitumor activity and target engagement in a subset of patients.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • WEE1 kinase is a regulator of cell cycle checkpoints and a therapeutic target in solid tumors.
  • Debio 0123 is an orally administered WEE1 inhibitor.
  • Phase 1 trials are crucial for assessing novel cancer therapeutics.

Purpose of the Study:

  • To evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of Debio 0123 in patients with advanced solid tumors.
  • To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Debio 0123.
  • To assess target engagement of Debio 0123 through pharmacodynamic markers.

Main Methods:

  • A dose-escalation phase 1 clinical trial was conducted.
  • Patients with relapsed/refractory advanced solid tumors received Debio 0123 orally, once daily.
  • Safety, antitumor activity, pharmacokinetics, and pharmacodynamics were assessed.

Main Results:

  • Twenty-seven patients were treated with Debio 0123 at doses from 30 to 350 mg.
  • The MTD and RP2D were determined to be 260 mg once daily.
  • Treatment-related adverse events included increased blood creatinine and QTcF prolongation; Grade 3 events occurred in 33.3% of patients.
  • Pharmacokinetics were proportional up to 350 mg.
  • Target engagement (decreased CDC2 phosphorylation) was observed at doses ≥200 mg.
  • Eight patients (32%) achieved stable disease, with 5 showing tumor regressions.

Conclusions:

  • Debio 0123 demonstrated a manageable toxicity profile and linear pharmacokinetics.
  • Target engagement was confirmed at doses ≥200 mg.
  • The observed antitumor activity in a subset of heavily pre-treated patients supports further investigation of Debio 0123.
Keywords:
CDC2CDK1Debio 0123Relapsed/refractory advanced solid tumorsWEE1 inhibitor

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