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 | AZD-7648|AZD 7648 | DNA_PK Inhibitor 9 | AZD7648 is an inhibitor of DNA-dependent protein kinase (DNA-PK), which potentially enhances genomic instability and sensitizes tumor cells to DNA-damaging agents (PMID: 31699977, PMID: 31851518). | |
| Olaparib | Lynparza | AZD2281|KU-0059436 | PARP Inhibitor (Pan) 30 | 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). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 |
| TP53 mutant | ovarian cancer | predicted - sensitive | AZD7648 + Olaparib | Preclinical - Pdx | Actionable | In a preclinical study, AZD7648 and Lynparza (olaparib) combination treatment induced tumor regression in a patient-derived xenograft (PDX) model of ovarian cancer harboring TP53 mutation and wild-type ATM (PMID: 31699977). | 31699977 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| 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 | Completed | USA | GBR | 0 |
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