Therapy Detail

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Therapy Name AZD7648 + Olaparib
Synonyms
Therapy Description

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Drug Name Trade Name Synonyms Drug Classes Drug Description
AZD7648 DNA_PK Inhibitor 6 AZD7648 is an inhibitor of DNA-dependent protein kinase, which potentially enhances genomic instability and sensitizes tumor cells to DNA-damaging agents (PMID: 31699977).
Olaparib Lynparza AZD2281|KU-0059436 PARP Inhibitor (Pan) 19 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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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown ovarian cancer not applicable AZD7648 + Olaparib Preclinical - Cell culture Actionable In a preclinical study, AZD7648 and Lynparza (olaparib) combination treatment inhibited viability of ovarian cancer cell lines harboring wild-type ATM in culture (PMID: 31699977). 31699977
Unknown unknown head and neck cancer not applicable AZD7648 + Olaparib Preclinical - Pdx Actionable In a preclinical study, AZD7648 and Lynparza (olaparib) combination treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of head and neck cancer harboring mutant TP53 and wild-type ATM (PMID: 31699977). 31699977
ATM del lung non-small cell carcinoma sensitive AZD7648 + Olaparib Preclinical - Cell culture Actionable In a preclinical study, AZD7648 treatment increased sensitivity to Lynparza (olaparib), inducing cell cycle arrest and inhibiting viability of ATM knockout non-small cell lung carcinoma cells in culture (PMID: 31699977). 31699977
ATM del head and neck cancer sensitive AZD7648 + Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, AZD7648 treatment increased sensitivity to Lynparza (olaparib), resulting in inhibition of Dna-pk phosphorylation, reduced cell viability, genomic instability, cell cycle arrest, and apoptosis in a head and neck cancer cell line with ATM deletion in culture, and inhibition of tumor growth and complete tumor regression in a cell line xenograft model (PMID: 31699977). 31699977

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Clinical Trial Phase Therapies Title Recruitment Status
NCT03907969 Phase Ib/II AZD7648 + Pegylated liposomal-doxorubicin AZD7648 + Olaparib AZD7648 A Clinical Trial to Evaluate AZD7648 Alone and in Combination With Other Anti-cancer Agents in Patients With Advanced Cancers Active, not recruiting


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