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Updated: Nov 4, 2025

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
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Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in

Mark R Middleton1, Emma Dean2,3, Thomas R J Evans4

  • 1Department of Oncology, University of Oxford, Oxford, UK.

British Journal of Cancer
|May 27, 2021
PubMed
Abstract

Insights

Berzosertib combined with gemcitabine showed preliminary efficacy and was well tolerated in patients with advanced solid tumors. This combination therapy is a promising option for difficult-to-treat cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Berzosertib is a novel, potent inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR).
  • ATR pathway inhibition is a potential strategy for overcoming chemotherapy resistance in solid tumors.

Purpose of the Study:

  • To assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of berzosertib in combination with gemcitabine, with or without cisplatin.
  • To determine the recommended Phase 2 dose (RP2D) for this combination therapy in patients with advanced solid tumors.

Main Methods:

  • A Phase 1, 3+3 dose-escalation study.
  • Intravenous administration of berzosertib, gemcitabine, and optional cisplatin.
  • Evaluation of dose-limiting toxicities (DLTs), PK parameters, and objective response rates.

Main Results:

  • The recommended Phase 2 dose (RP2D) was established as berzosertib 210 mg/m² (days 2 and 9) + gemcitabine 1000 mg/m² (days 1 and 8) every 3 weeks.
  • Berzosertib plus gemcitabine was generally well tolerated, with manageable toxicities.
  • Preliminary efficacy was observed, with most patients achieving a best response of partial response or stable disease.

Conclusions:

  • Berzosertib in combination with gemcitabine demonstrated acceptable safety and preliminary signs of efficacy in patients with advanced solid tumors.
  • Further investigation of this combination in larger trials is warranted.

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