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Olaparib 200-300 mg BID, daily
Olaparib inhibits PARP enzymes to block DNA single-strand break repair, inducing synthetic lethality in BRCA-mutant and HR-deficient cancers.
Olaparib (200–300 mg BID) is a PARP inhibitor originally developed by AstraZeneca and studied by Repare Therapeutics, now discontinued from Repare's pipeline. The drug inhibits poly(ADP-ribose) polymerase (PARP), a DNA repair enzyme, causing synthetic lethality in BRCA-mutant and homologous recombination-deficient tumors. While olaparib achieved FDA approval under AstraZeneca's Lynparza brand for multiple oncology indications (ovarian, breast, pancreatic, and prostate cancers), Repare's development program has been terminated, indicating the company deprioritized this asset. Clinical trials show olaparib's efficacy in combination regimens (with vorinostat, sapacitabine, radiotherapy, and immunotherapy) across breast, ovarian, and lung cancers, though Repare's Phase 1 combination study with RP-3467 was terminated. The commercial significance lies in olaparib's established market presence under Lynparza (AstraZeneca), which generated substantial revenue; however, Repare's discontinuation suggests limited differentiation or strategic pivot toward proprietary assets.
At a glance
| Generic name | Olaparib 200-300 mg BID, daily |
|---|---|
| Also known as | RP-3467 at assigned dose and schedule, Lynparza |
| Sponsor | Repare Therapeutics |
| Drug class | PARP inhibitor (DNA damage response inhibitor) |
| Target | PARP1 and PARP2 (poly(ADP-ribose) polymerase enzymes) |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | discontinued |
Mechanism of action
Olaparib works by blocking poly(ADP-ribose) polymerase (PARP), an enzyme that repairs single-strand DNA breaks. In normal cells, when a single-strand break occurs, PARP detects and repairs it. However, in cancer cells with BRCA1/BRCA2 mutations or other homologous recombination (HR) deficiencies, the cell cannot repair double-strand breaks through the normal HR pathway. When olaparib blocks PARP, single-strand breaks accumulate and convert into lethal double-strand breaks during DNA replication. Because these cancer cells cannot repair double-strand breaks (due to HR deficiency), they die—a phenomenon called synthetic lethality. This mechanism is particularly effective in BRCA-mutant ovarian, breast, and pancreatic cancers, where HR repair is already compromised. Olaparib can also be combined with chemotherapy, radiotherapy, or immunotherapy to enhance DNA damage and overcome resistance mechanisms.
Approved indications
Pipeline indications
- Relapsed/refractory metastatic breast cancer (in combination with vorinostat) — Phase 1
- BRCA-mutant breast cancer (in combination with sapacitabine) — Phase 1
- Advanced solid tumors (RP-3467 + olaparib combination) — Phase 1
- High-grade serous ovarian cancer (idetrexed + olaparib) — Phase 1
- Small-cell lung cancer (olaparib + low-dose radiotherapy) — Phase 1
Common side effects
Key clinical trials
- A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032) (PHASE3)
- Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can... (PHASE1, PHASE2)
- Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer (PHASE2)
- Long-term Safety and Efficacy Extension Study for Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab (MK-3475) Study (MK-3475-587/KEYNOTE-587) (PHASE3)
- Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer (PHASE1)
- Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03) (PHASE2)
- I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (PHASE2)
- To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy. (PHASE2)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Olaparib 200-300 mg BID, daily CI brief — competitive landscape report
- Olaparib 200-300 mg BID, daily updates RSS · CI watch RSS
- Repare Therapeutics portfolio CI