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Therapy Name | Ceralasertib + Olaparib |
Synonyms | |
Therapy Description | |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Ceralasertib | AZD6738|AZD-6738 | ATR Inhibitor 16 | 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) 31 | 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 (mCRPC) with deleterious or suspected deleterious germline or somatic homologous recombination repair gene mutations who progressed following enzalutamide or abiraterone, in combination with abiraterone in patients with mCRPC harboring deleterious or suspected deleterious BRCA mutations, 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). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
IDH1 R132H | Advanced Solid Tumor | sensitive | Ceralasertib + Olaparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell survival compared to Ceralasterib (AZD6738) alone in cells expressing IDH1 R132H in culture, and a longer delay in tumor growth in cell line xenograft models (PMID: 34027408). | 34027408 |
ATM inact mut | Advanced Solid Tumor | predicted - sensitive | Ceralasertib + Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an overall response rate of 20% (1/5) and a clinical benefit rate of 40% (2/5) in patients with advanced solid tumors harboring ATM inactivating mutations, including a durable complete response in a patient with breast cancer and a durable stable disease in a patient with adenoid cystic carcinoma of minor salivary gland (PMID: 34527850; NCT02576444). | 34527850 |
IDH1 R132S | cholangiocarcinoma | sensitive | Ceralasertib + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell viability compared to Ceralasertib (AZD6738) alone in cholangiocarcinoma cells harboring IDH1 R132S in culture (PMID: 34027408). | 34027408 |
ATM loss | head and neck cancer | predicted - sensitive | Ceralasertib + 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... |
ATM loss | triple-receptor negative breast cancer | predicted - sensitive | Ceralasertib + Olaparib | Phase II | Actionable | In a Phase II trial (plasmaMATCH), treatment with the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in limited efficacy in patients with advanced triple-negative breast cancer, with an objective response rate of 17.1% (12/70), but in patients with wild-type BRCA1/2 and ATM loss, resulted in a median progression-free survival of 3.4 vs 2.5 mo and response rate of 21.4 (3/14) vs 13.8% (4/29) in patients without loss of ATM (PMID: 37773077; NCT03182634). | 37773077 |
ATM LOH ATM inact mut | estrogen-receptor positive breast cancer | predicted - sensitive | Ceralasertib + Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an ongoing complete response for over 26 months in a patient with estrogen receptor-positive metastatic breast cancer harboring germline ATM mutation with accompanying loss of heterozygosity (LOH) (PMID: 34527850; NCT02576444). | 34527850 |
IDH2 R172S | chondrosarcoma | sensitive | Ceralasertib + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell viability compared to Ceralasertib (AZD6738) alone in chondrosarcoma cells harboring IDH2 R172S in culture (PMID: 34027408). | 34027408 |
IDH1 R132C | fibrosarcoma | sensitive | Ceralasertib + Olaparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater delay in tumor growth compared to Ceralasertib (AZD6738) alone in fibrosarcoma cell line xenograft models harboring IDH1 R132C (PMID: 34027408). | 34027408 |
ATM P1069fs ATM LOH | salivary gland adenoid cystic carcinoma | predicted - sensitive | Ceralasertib + Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (OLAPCO), Ceralasertib (AZD6738) and Lynparza (olaparib) combination treatment resulted in an ongoing 22% reduction in target lesions in a patient with adenoid cystic carcinoma of minor salivary gland harboring germline ATM P1069fs with accompanying loss of heterozygosity (LOH), who remained on treatment for over 26 months (PMID: 34527850; NCT02576444). | 34527850 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02576444 | Phase II | Adavosertib + Olaparib Olaparib Capivasertib + Olaparib Ceralasertib + Olaparib | OLAParib COmbinations (OLAPCO) | Terminated | USA | 0 |
NCT03682289 | Phase II | Ceralasertib + Olaparib Olaparib | Phase II Trial of AZD6738 Alone and in Combination With Olaparib | Recruiting | USA | 0 |
NCT03462342 | Phase II | Ceralasertib + Olaparib | Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer (CAPRI) | Active, not recruiting | USA | 0 |
NCT03182634 | Phase II | Fulvestrant Ceralasertib + Olaparib Capivasertib Fulvestrant + Neratinib | The UK Plasma Based Molecular Profiling of Advanced Breast Cancer to Inform Therapeutic CHoices (plasmaMATCH) Trial (plasmaMATCH) | Unknown status | GBR | 0 |
NCT03787680 | Phase II | Ceralasertib + Olaparib | Targeting Resistant Prostate Cancer With ATR and PARP Inhibition (TRAP Trial) | Active, not recruiting | USA | 0 |
NCT03878095 | Phase II | Ceralasertib + Olaparib | Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors | Active, not recruiting | USA | 0 |
NCT04417062 | Phase II | Ceralasertib + Olaparib | Olaparib With Ceralasertib in Recurrent Osteosarcoma | Recruiting | USA | 0 |
NCT04239014 | Phase II | Olaparib Ceralasertib + 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) | Withdrawn | USA | ITA | ESP | CAN | 0 |
NCT04065269 | Phase II | Ceralasertib + Olaparib Ceralasertib | ATr Inhibitor in Combination With Olaparib in Gynaecological Cancers With ARId1A Loss or no Loss (ATARI) | Recruiting | GBR | CAN | 0 |
NCT03330847 | Phase II | Adavosertib + Olaparib Olaparib Ceralasertib + Olaparib | To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy. | Active, not recruiting | USA | POL | NLD | ITA | IRL | GBR | FRA | ESP | DEU | CZE | CAN | BEL | 3 |
NCT04090567 | Phase II | Cediranib + Olaparib Ceralasertib + Olaparib | Olaparib With Cediranib or AZD6738 for the Treatment of Advanced or Metastatic Germline BRCA Mutated Breast Cancer | Recruiting | USA | 0 |
NCT02264678 | Phase Ib/II | Ceralasertib Carboplatin + Ceralasertib Ceralasertib + Durvalumab Ceralasertib + Olaparib | Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents | Recruiting | USA | HUN | GBR | FRA | ESP | CAN | BEL | AUS | 1 |