A Phase II Single Arm Pilot Study of the Chk1/2 Inhibitor (LY2606368) In BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Triple Negative Breast Cancer, and High Grade Serous Ovarian Cancer

Trial ID # NCT02203513
Phase II
Drug Class Cell Cycle Inhibitors: CHK1/2
Drug Name Prexasertib
Alternate Drug Names LY2606368, checkpoint kinase 1 inhibitor LY2606368
Drugs in Trial Prexasertib
Eligible Participant

Recurrent gBRCA1/2 MUT ovarian cancer or gBRCA1/2 WT high grade serous ovarian cancer

Patients Enrolled

153 (28 ovarian gBRCA WT; median 5 prior therapies)

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, DCR, PFS, evaluated per RECIST

Biomarkers

gBRCA1/2; Exploratory: CCNE1, CCNE1 protein

Efficacy

ORR: 29% (8PR, n=28)
PFS: 7.4 months (n=24)

Exploratory analysis Pt-R/Pt-Rf:
ORR: 32% (6PR, n=19)
DCR: 58% (6PR, 5SD, n=19)
PFS: 7.5 months (data extracted from publication)

Clinically Significant Adverse Events

Serious AE: grade 3 febrile neutropenia (n=2)
Grade 3-4 AE: neutropenia (transient) (93%), leukopenia (82%), thrombocytopenia (25%), anemia (11%)

Conclusion

Promising activity in heavily pretreated platinum-resistant gBRCA1/2 WT patients and also with CCNE1 aberrations

Reference

Lee J-M et al. Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study. Lancet Oncol (2018) 19(2):209-215
https://www.ncbi.nlm.nih.gov/pubmed/29361470