The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial

Elena Giudice, Tzu-Ting Huang, Jayakumar R. Nair, Grant Zurcher, Ann McCoy, Darryl Nousome, Marc R. Radke, Elizabeth M. Swisher, Stanley Lipkowitz, Kristen Ibanez, Duncan Donohue, Tyler Malys, Min-Jung Lee, Bernadette Redd, Elliot Levy, Shraddha Rastogi, Nahoko Sato, Jane B. Trepel and Jung-Min Lee ()
Additional contact information
Elena Giudice: National Cancer Institute (NCI), National Institutes of Health (NIH)
Tzu-Ting Huang: National Cancer Institute (NCI), National Institutes of Health (NIH)
Jayakumar R. Nair: National Cancer Institute (NCI), National Institutes of Health (NIH)
Grant Zurcher: National Cancer Institute (NCI), National Institutes of Health (NIH)
Ann McCoy: National Cancer Institute (NCI), National Institutes of Health (NIH)
Darryl Nousome: CCR, NCI, NIH
Marc R. Radke: University of Washington
Elizabeth M. Swisher: University of Washington
Stanley Lipkowitz: National Cancer Institute (NCI), National Institutes of Health (NIH)
Kristen Ibanez: National Cancer Institute (NCI), National Institutes of Health (NIH)
Duncan Donohue: Computer and Statistical Services, Data Management Services, Inc. (a BRMI company), NCI
Tyler Malys: Computer and Statistical Services, Data Management Services, Inc. (a BRMI company), NCI
Min-Jung Lee: CCR, NCI, NIH
Bernadette Redd: CCR, NCI, NIH
Elliot Levy: CCR, NCI, NIH
Shraddha Rastogi: CCR, NCI, NIH
Nahoko Sato: CCR, NCI, NIH
Jane B. Trepel: CCR, NCI, NIH
Jung-Min Lee: National Cancer Institute (NCI), National Institutes of Health (NIH)

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6). Among the 39 RECISTv1.1-evaluable patients, ORR was 33.3% in cohort 5 and 28.6% in cohort 6. Primary endpoint was not evaluable due to early stop of the trial. The median PFS was 4 months in cohort 5 and 6 months in cohort 6. Toxicity was manageable. Translational research was an exploratory endpoint. Potential biomarkers were investigated using pre-treatment fresh biopsies and serial blood samples. Transcriptomic analysis revealed high levels of DNA replication-related genes (POLA1, POLE, GINS3) associated with lack of clinical benefit [defined post-hoc as PFS

Date: 2024
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DOI: 10.1038/s41467-024-47215-6

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