Olaparib Monotherapy in HRRm or HRD Positive Cancer
Research type
Research Study
Full title
A Phase 2 Study of Olaparib Monotherapy in Participants with Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer
IRAS ID
255158
Contact name
Elizabeth Plummer
Contact email
Sponsor organisation
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eudract number
2018-003007-19
Duration of Study in the UK
4 years, 5 months, 0 days
Research summary
Human cancers exhibit genomic (DNA) instability and an increased mutation rate due to underlying defects in DNA repair. The deficiencies make cancer cells more dependent on the remaining methods of DNA repair and targeting these remaining pathways is expected to have a much greater impact on the survival of the tumour cells than on normal cells.\n\nThe study drug olaparib is a type of targeted therapy called a PARP inhibitor. PARP is an enzyme (protein) needed for repairing single strand breaks (SSBs) in DNA. Inhibiting PARP prevents the repair of SSBs, which are then converted to the more serious DNA double strand breaks (DSBs). DSBs can be repaired in normal cells by a process called homologous recombination repair (HRR), but some tumours carry mutations that mean they are unable to perform HRR. The mutations can be found in at least 15 genes involved in HRR, including BRCA1 and BRCA2. By using olaparib to help stop PARP in tumours with these mutations, it means that the DNA damage isn’t repaired, and this can lead to cancer cell death. \n\nApproximately 370 participants with previously treated, advanced (unresectable and/or metastatic) HRR mutation (HRRm) and/or HRD-positive solid tumours will be enrolled onto this Phase II, open-label study which will last approximately 4.5 years. Each participant will receive olaparib orally, twice daily, to test the safety and efficacy of the study drug. \n\nParticipants will be enrolled into two cohorts:\n\nCohort 1 - BRCA1/2 mutated\nCohort 2 - HRRm and HRD positive and BRCA1/2 non-mutated\n\nThe study is funded by Merck Sharp and Dohme Limited and will take place at 3 study centres in UK.\n\n
REC name
Wales REC 3
REC reference
18/WA/0390
Date of REC Opinion
15 Feb 2019
REC opinion
Further Information Unfavourable Opinion