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Lookup NU author(s): Professor Ruth Plummer
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s). Background: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). We assessed multiple ascending doses of berzosertib + gemcitabine ± cisplatin in patients with resistant/refractory advanced solid tumours. Methods: We evaluated the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of intravenous berzosertib + gemcitabine ± cisplatin using a standard 3 + 3 dose-escalation design. The starting doses were berzosertib 18 mg/m2, gemcitabine 875 mg/m2 and cisplatin 60 mg/m2. Results: Fifty-two patients received berzosertib + gemcitabine and eight received berzosertib + gemcitabine + cisplatin. Four patients receiving berzosertib + gemcitabine had a total of seven dose-limiting toxicities (DLTs) and three receiving berzosertib + gemcitabine + cisplatin had a total of three DLTs. Berzosertib 210 mg/m2 (days 2 and 9) + gemcitabine 1000 mg/m2 (days 1 and 8) Q3W was established as the recommended Phase 2 dose (RP2D); no RP2D was determined for berzosertib + gemcitabine + cisplatin. Neither gemcitabine nor cisplatin affected berzosertib PK. Most patients in both arms achieved a best response of either partial response or stable disease. Conclusions: Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs. Clinical trial identifier: NCT02157792.
Author(s): Middleton MR, Dean E, Evans TRJ, Shapiro GI, Pollard J, Hendriks BS, Falk M, Diaz-Padilla I, Plummer R
Publication type: Article
Publication status: Published
Journal: British Journal of Cancer
Year: 2021
Volume: 125
Issue: 4
Pages: 510-519
Print publication date: 17/08/2021
Online publication date: 26/05/2021
Acceptance date: 15/04/2021
Date deposited: 23/06/2022
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41416-021-01405-x
DOI: 10.1038/s41416-021-01405-x
PubMed id: 34040175
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