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Oncology outcomes

Can CHK1 blockade help BRCA-wild-type resistant ovarian cancer?

Giudice E, Huang TT, Nair JR, et al. · Nature communications · 2024

Open access · cc by · source: Europe PMC

In 49 heavily pretreated BRCAwt platinum-resistant HGSOC patients, prexasertib yielded ~29–33% ORR with manageable but frequent neutropenia before early trial stop.

How this study connects

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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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Inspect source passages

Can CHK1 blockade help BRCA-wild-type resistant ovarian cancer?

These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.

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)
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Key findings

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.

Methodology

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.

Limitations

Not a randomized comparative efficacy trial; early stop limited definitive primary-endpoint evaluation and generalizability.

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