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A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer

Lookup NU author(s): Professor Gareth Veal



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023, The Author(s). Background: This was a first-in-human Phase 1/2 open-label dose-escalation study of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737. Methods: Patients with advanced solid tumours enrolled in dose-escalation cohorts and received SRA737 monotherapy orally on a continuous daily (QD) dosing schedule in 28-day cycles. Expansion cohorts included up to 20 patients with prospectively selected, pre-specified response predictive biomarkers. Results: In total, 107 patients were treated at dose levels from 20–1300 mg. The maximum tolerated dose (MTD) of SRA737 was 1000 mg QD, the recommended Phase 2 dose (RP2D) was 800 mg QD. Common toxicities of diarrhoea, nausea and vomiting were generally mild to moderate. Dose-limiting toxicity at daily doses of 1000 and 1300 mg QD SRA737 included gastrointestinal events, neutropenia and thrombocytopenia. Pharmacokinetic analysis at the 800 mg QD dose showed a mean C min of 312 ng/mL (546 nM), exceeding levels required to cause growth delay in xenograft models. No partial or complete responses were seen. Conclusions: SRA737 was well tolerated at doses that achieved preclinically relevant drug concentrations but single agent activity did not warrant further development as monotherapy. Given its mechanism of action resulting in abrogating DNA damage repair, further clinical development of SRA737 should be as combination therapy. Clinical trial registration: NCT02797964.

Publication metadata

Author(s): Kristeleit R, Plummer R, Jones R, Carter L, Blagden S, Sarker D, Arkenau T, Evans TRJ, Danson S, Symeonides SN, Veal GJ, Klencke BJ, Kowalski MM, Banerji U

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2023

Volume: 129

Pages: 38-45

Print publication date: 27/07/2023

Online publication date: 29/04/2023

Acceptance date: 13/04/2023

Date deposited: 11/05/2023

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Springer Nature


DOI: 10.1038/s41416-023-02279-x


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Funder referenceFunder name
Sierra Oncology, Inc.