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.
- 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.