Prexasertib, an investigational kinase inhibitor of checkpoint kinases 1 and 2, demonstrates promising activity in patients with BRCA wild type sporadic high-grade serous ovarian cancer, according to a study presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1

Checkpoint kinases 1 and 2 are involved in cell cycle regulation in tumors with p53 dysfunction, such as high-grade serous ovarian cancer. Prexasertib has shown preliminary activity in patients with cancer in phase 1 trials; researchers evaluated efficacy of prexasertib in a subpopulation with high-grade serous ovarian cancer.

For the phase 2 trial (ClinicalTrials.gov Identifier: NCT02203513), investigators enrolled patients with recurrent sporadic high-grade serous ovarian cancer who tested negative for a BRCA mutation or had a negative family history of breast and ovarian cancer syndrome (cohort 1) or with a deleterious germline BRCA1/2 mutation (cohort 2). Median number of prior therapies was 5 and 7, respectively.

So far, 15 patients with sporadic high-grade serous ovarian cancer and 7 with germline BRCA mutation-associated ovarian cancer have been treated with prexasertib monotherapy.

The objective response rate was 38% among the 13 evaluable patients in cohort 1. Of those, 2 had platinum-sensitive disease and 3 had platinum-resistant disease. Four of the evaluable 6 patients in cohort 2 achieved stable disease for 4 months or greater, but no patients had a response to treatment.

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The most common grade 3 to 4 treatment-emergent adverse events were neutropenia, thrombocytopenia, febrile neutropenia, and diarrhea. Thirteen patients required growth factor support to treat febrile neutropenia or to minimize the risk for treatment interruptions.

Reference

  1. Lee J, Karzai FH, Zimmer A, et al. A phase II study of the cell cycle checkpoint kinases 1 and 2 inhibitor (LY26063368; prexasertib monomesylate monohydrate) in sporadic high-grade serous ovarian cancer (HGSOC) and germline BRCA mutation-associated ovarian cancer (gBRCAm+ OvCa). Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.