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

Recurrent high grade serous ovarian cancer

28 HGS gBRCA WT; median 5 prior therapies; 79% Pt-R/Pt-Rf; 22 HGS gBRCA MUT; median 5 prior therapies

Recurrence

Open-Label, Non-randomized

CBR, ORR, PFS, evaluated per RECIST

gBRCA1/2; Exploratory: CCNE1, CCNE1 protein

BRCA WT:
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)

BRCA MUT:
ORR: 11.1% (1CR, 1PR, n=18)
DCR: 77.8% (1CR, 1PR, 12SD, n=18)

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

Promising activity in heavily pretreated BRCA WT patients and also with CCNE1 alterations, but modest activity in BRCA MUT patients

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

Lampert EJ et al. Prexasertib, a cell cycle checkpoint kinase 1 inhibitor, in BRCA mutant recurrent high-grade serous ovarian cancer (HGSOC): A proof-of-concept single arm phase II study. J Clin Oncol (2020) 38: (suppl; abstr 6038)
https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.6038

Lampert EJ et al. Poster
https://www.clearityfoundation.org/wp-content/uploads/2020/07/Prexasertib-HGS-BRCA-MUT-cohort-ASCO-2020.pdf