Therapy Detail
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| Therapy Name | AZD6738 + Olaparib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| AZD6738 | Ceralasertib|AZD-6738 | ATR Inhibitor 12 | Ceralasertib (AZD6738) is an inhibitor of ATR, which may enhance the sensitivity of chemotherapeutic agents, potentially resulting in tumor regression (PMID: 26517239, PMID: 31836456). | |
| Olaparib | Lynparza | AZD2281|KU-0059436 | PARP Inhibitor (Pan) 20 | Lynparza (olaparib) binds to and inhibits PARP, resulting in inhibition of DNA repair and lethality in homologous-recombination deficient cells, and may be a sensitizing agent for chemotherapy and radiotherapy (PMID: 25028150, PMID: 24225019). Lynparza (olaparib) is FDA approved for treatment of ERBB2 (HER2)-negative breast cancer with deleterious or suspected deleterious germline BRCA mutations, ovarian cancer with deleterious or suspected deleterious germline BRCA mutations and received 3 or more prior therapies, metastatic pancreatic adenocarcinoma with deleterious or suspected deleterious germline BRCA mutations as a maintenance therapy, metastatic castration-resistant prostate cancer with deleterious or suspected deleterious germline or somatic homologous recombination repair gene mutations who progressed following enzalutamide or abiraterone, as a maintenance therapy in recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer and in epithelial ovarian, fallopian tube or primary peritoneal cancer with deleterious or suspected deleterious germline or somatic BRCA mutation, and in combination with Avastin (bevacizumab) as maintenance therapy in HDR defective epithelial ovarian, fallopian tube or primary peritoneal cancer as defined by deleterious or suspected deleterious BRCA mutation, and/or genomic instability (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ATM loss | head and neck cancer | predicted - sensitive | AZD6738 + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of AZD6738 and Lynparza (olaparib) resulted in a synergistic effect, demonstrating cell death in head and neck cancer cells harboring ATM loss in culture (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C60). | detail... |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT02576444 | Phase II | Adavosertib + Olaparib Olaparib Capivasertib + Olaparib AZD6738 + Olaparib | OLAParib COmbinations (OLAPCO) | Active, not recruiting |
| NCT03878095 | Phase II | AZD6738 + Olaparib | Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors | Recruiting |
| NCT04417062 | Phase II | AZD6738 + Olaparib | Olaparib With Ceralasertib in Recurrent Osteosarcoma | Not yet recruiting |
| NCT03682289 | Phase II | AZD6738 + Olaparib Olaparib | Phase II Trial of AZD6738 Alone and in Combination With Olaparib | Recruiting |
| NCT03462342 | Phase II | AZD6738 + Olaparib | Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer (CAPRI) | Recruiting |
| NCT03787680 | Phase II | AZD6738 + Olaparib | Targeting Resistant Prostate Cancer With ATR and PARP Inhibition (TRAP Trial) | Recruiting |
| NCT04239014 | Phase II | Olaparib AZD6738 + Olaparib | A Study to Evaluate the Effectiveness and Tolerability of a Second Maintenance Treatment in Participants With Ovarian Cancer, Who Have Previously Received Polyadenosine 5'Diphosphoribose [Poly (ADP Ribose)] Polymerase Inhibitor (PARPi) Treatment. (DUETTE) | Recruiting |
| NCT02264678 | Phase Ib/II | AZD6738 AZD6738 + Carboplatin AZD6738 + Durvalumab AZD6738 + Olaparib | Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents | Recruiting |
| NCT04090567 | Phase II | Cediranib + Olaparib AZD6738 + Olaparib | Olaparib With Cediranib or AZD6738 for the Treatment of Advanced or Metastatic Germline BRCA Mutated Breast Cancer | Recruiting |
| NCT03330847 | Phase II | Adavosertib + Olaparib Olaparib AZD6738 + Olaparib | To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy. | Recruiting |
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