Therapy Detail
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| Therapy Name | Doxorubicin + Olaparib + Quizartinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Doxorubicin | Adriamycin | Adria|ADR|Doxorubicin hydrochloride|Hydroxydaunorubicin | Chemotherapy - Anthracycline 13 TOPO2 inhibitor 5 | Adriamycin (doxorubicin) is an anthracycline chemotherapeutic, in a non-liposomal formulation, which intercalates into DNA and inhibits topoisomerase II (PMID: 24367159). Doxorubicin is FDA approved for multiple cancer types (FDA.gov). |
| 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). |
| Quizartinib | Vanflyta | AC220 | FLT3 Inhibitor 69 | Vanflyta (quizartinib) is a small molecule that selectively inhibits FLT3, which may induce apoptosis and inhibit tumor growth (PMID: 19654408, PMID: 23497317). Vanflyta (quizartinib) is FDA-approved for use in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, in patients with newly diagnosed acute myeloid leukemia harboring FLT3 ITD mutations (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| DNMT3A loss FLT3 exon 14 ins TET2 loss | acute myeloid leukemia | sensitive | Doxorubicin + Olaparib + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) increased DNA double-strand breaks and decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 and DNMT3A loss in culture (PMID: 34215619). | 34215619 |
| DNMT3A mut FLT3 exon 14 ins TET2 mut | acute myeloid leukemia | sensitive | Doxorubicin + Olaparib + Quizartinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and DNMT3A and TET2 mutations along with an NPM1 mutation in culture (PMID: 34215619). | 34215619 |
| FLT3 exon 14 ins TET2 mut | acute myeloid leukemia | sensitive | Doxorubicin + Olaparib + Quizartinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and a TET2 mutation along with an NPM1 mutation in culture (PMID: 34215619). | 34215619 |
| FLT3 exon 14 ins TET2 loss | acute myeloid leukemia | sensitive | Doxorubicin + Olaparib + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) increased DNA double-strand breaks and decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 loss in culture (PMID: 34215619). | 34215619 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|
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