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 checkpoint kinase 1 inhibitor LY2606368, LY2606368
Drugs in Trial Prexasertib
Eligible Participant

Recurrent gBRCA MUT ovarian cancer or gBRCA WT high grade serous ovarian cancer

Patients Enrolled

153 (28 HGS or high grade endometrioid gBRCA WT ovarian cancer; median 5 prior therapies)

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

CBR, ORR, PFS, evaluated per RECIST

Biomarkers

gBRCA1/2; Exploratory: CCNE1, CCNE1 protein

Efficacy

ORR: 29% (8PR, n=28)
PFS: 7.4 months (n=24)
19/24 patients had CCNE1 mRNA upregulation, AMP or CCNE1 protein overexpression; 12/19 had PFS>6 months

Exploratory analysis Pt-R/Pt-Rf:
ORR: 32% (6PR, n=19); CBR: 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 gBRCA1/2 WT patients and also with CCNE1 alterations

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