Olaparib for patients with tumors harboring alterations in homologous recombination repair genes: Results from the drug rediscovery protocol.

ABSTRACT: BRCA1/2 are crucial in the homologous recombination repair (HRR) pathway, with loss-of-function (LoF) alterations predicting sensitivity to PARP-inhibitors (PARPi). Whether other HRR-gene alterations confer PARPi sensitivity remains unclear. In the Drug Rediscovery Protocol, patients receive off-label drugs matched to their tumor molecular profile. Here, olaparib efficacy and safety were evaluated in adult patients with treatment-refractory, progressive malignancies harboring LoF alterations in ATM (cohort A) or other HRR-genes including CDK12, PPP2R2A, CHEK1/2, and RAD51B (cohort B). Primary endpoints were clinical benefit (CB: confirmed objective response or stable disease ≥16 weeks) and safety. Pre-treatment biopsies were analyzed by whole-genome sequencing (WGS) for target validation.

SUBMITTER: Spiekman IAC 

PROVIDER: S-EPMC12811198 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature