Can CHK1 blockade help BRCA-wild-type resistant ovarian cancer?
In 49 heavily pretreated BRCAwt platinum-resistant HGSOC patients, prexasertib yielded ~29–33% ORR with manageable but frequent neutropenia before early trial stop.
Source
The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial
Study at a glance
- Design
- Other — Open-label single-arm phase 2 basket cohorts (NCT02203513 cohorts 5–6) of IV prexasertib in BRCAwt platinum-resistant HGSOC; early sponsorship stop
- N
- N=49 · 24 biopsiable (cohort 5) + 25 non-biopsiable (cohort 6); 39 RECIST-evaluable
- Population
- Adults with BRCA wild-type platinum-resistant recurrent high-grade serous ovarian/related carcinoma
- Outcome
- ORR (primary), safety, PFS; exploratory replication-stress biomarkers
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Can CHK1 blockade help BRCA-wild-type resistant ovarian cancer?
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Which patients were enrolled in this report?
49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6)
How did cohorts 5 and 6 differ?
biopsiable disease (cohort 5), or without biopsiable disease (cohort 6)
What they did
An NCI open-label phase 2 enrolled cohorts with or without biopsiable disease, giving IV prexasertib 105 mg/m² every 2 weeks, assessing RECIST ORR, PFS, safety, and exploratory biopsy/blood biomarkers.
What they found
Among 39 evaluable patients, ORR was 33.3% (cohort 5) and 28.6% (cohort 6); median PFS 4 vs 6 months; neutropenia in 85.7%. High POLA1/POLE/GINS3 transcripts tracked with PFS <6 months.
The limits
What it doesn't show
Not a randomized comparative efficacy trial; early stop limited definitive primary-endpoint evaluation and generalizability.
Key terms
- Prexasertib
- CHK1 inhibitor tested as monotherapy in this phase 2 study.
- BRCAwt HGSOC
- High-grade serous ovarian carcinoma without BRCA1/2 mutation—majority of HGSOC.
- Platinum-resistant
- Recurrent disease with limited platinum benefit; high unmet need.
- ORR / PFS
- Objective response rate and progression-free survival endpoints.
- Replication stress
- DNA replication vulnerability that may sensitize tumors to ATR/CHK1 blockade.
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What clinical setting was studied?
Common questions
Were patients BRCA-mutated?
No—BRCA wild-type status was required.
Did it shrink tumors?
Yes in a minority—about one-third of evaluable patients responded by RECIST.
Main safety issue?
Cytopenias, especially neutropenia (~86%).
Why early stop?
Company withdrew investigational drug sponsorship/supply; primary endpoint not evaluable as planned.
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