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Therapy Name Midostaurin
Synonyms
Therapy Description

Rydapt (midostaurin) is a multi-kinase inhibitor with activity against FLT3, KIT, PDGFRB, KDR (VEGFR2) and PKC, with higher selectivity for conventional PKC isoforms, which induces cell cycle arrest and apoptosis (PMID: 12124173, PMID: 23127174, PMID: 15914319). Rydapt (midostaurin) is FDA approved for FLT3-mutant AML in combination with chemotherapy, and is approved for use in aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm, or mast cell leukemia as a single therapy (FDA.gov).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Midostaurin Rydapt PKC412|CGP 41251 CSF1R Inhibitor 23 FLT3 Inhibitor 54 KIT Inhibitor 50 PKC alpha Inhibitor 6 PKC beta Inhibitor 6 PKC Inhibitor (Pan) 10 VEGFR2 Inhibitor 35 Rydapt (midostaurin) is a multi-kinase inhibitor with activity against FLT3, KIT, PDGFRB, KDR (VEGFR2) and PKC, with higher selectivity for conventional PKC isoforms, which induces cell cycle arrest and apoptosis (PMID: 12124173, PMID: 23127174, PMID: 15914319). Rydapt (midostaurin) is FDA approved for FLT3-mutant AML in combination with chemotherapy, and is approved for use in aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm, or mast cell leukemia as a single therapy (FDA.gov).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 S451F Advanced Solid Tumor decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 S451F demonstrated decreased sensitivity to inhibition of FLT3 phosphorylation and growth by Rydapt (midostaurin) in culture, when compared to cells expressing other FLT3 activating mutations (PMID: 18068628). 18068628
KIT V560G mast cell neoplasm sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of mast cells harboring KIT V560G in culture (PMID: 31085175). 31085175
FLT3 exon 14 ins FLT3 A627P hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 22858906). 22858906
KIT N655K KIT D816V Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT N655K demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). 31270078
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L in culture (PMID: 31309543). 31309543
KIT T670V KIT D816V Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670V were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078). 31270078
FLT3 exon 14 ins Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) demonstrated efficacy in inhibiting proliferation and viability of transformed cells expressing a FLT3-ITD mutation in culture (PMID: 12124173). 12124173
CBL Y371del FLT3 pos hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371del in culture (PMID: 31943762). 31943762
FLT3 exon 14 ins hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
KIT N822K acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of acute myeloid leukemia cells harboring KIT N822K in culture (PMID: 31085175). 31085175
KIT V654A KIT D816V Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT V654A demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). 31270078
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). detail...
RUNX1 - RUNX1T1 KIT N822K acute myeloid leukemia decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) demonstrated reduced ability to inhibit Kit phosphorylation and growth of acute myeloid leukemia cell lines harboring KIT N822K and RUNX1-RUNX1T1 in culture compared to other kinase inhibitors (PMID: 31309543). 31309543
KIT V560G KIT D816V mast cell neoplasm sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of mast cells harboring KIT D816V and KIT V560G in culture (PMID: 31085175). 31085175
FLT3 D835Y Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) inhibited FLT3 phosphorylation and resulted in decreased proliferation and viability of transformed cells expressing FLT3 D835Y in culture (PMID: 12124173). 12124173
FLT3 wild-type Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3 phosphorylation in transformed cells expressing wild-type FLT3 in culture (PMID: 12124173). 12124173
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 I836del cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited phosphorylation of FLT3, ERK, and STAT5, and growth of transformed cells expressing FLT3 I836del in culture (PMID: 17827387). 17827387
KIT D816V acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). 31309543
KIT exon 11 del KIT D816E gastrointestinal stromal tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT D816E in culture (PMID: 31085175). 31085175
FLT3 R834Q Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3-induced phosphorylation of ERK1/2 and reduced growth of transformed cells expressing FLT3 R834Q in culture (PMID: 18068628). 18068628
KIT D677N KIT D816V Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT D677N demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). 31270078
KIT T670A KIT D816V Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670A were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078). 31270078
FLT3 Y842C acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) induced cell death and inhibited FLT3 activation and downstream STAT5 activation in primary acute myeloid leukemic blasts harboring FLT3 Y842C in culture (PMID: 15345593). 15345593
PDGFRA D842V Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of transformed cells expressing PDGFRA D842V in culture (PMID: 31085175). 31085175
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). detail...
CBL Y371H FLT3 wild-type hematologic cancer sensitive Midostaurin Preclinical Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture, reduced leukemia burden and prolonged survival in animal models (PMID: 31309543). 31309543
CBL Y371H FLT3 pos hematologic cancer sensitive Midostaurin Preclinical - Cell line xenograft Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Y371H in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Y371H (PMID: 31943762). 31943762
KIT T670I KIT D816V Advanced Solid Tumor decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670I demonstrated a decreased response compared to cells expressing KIT D816V alone when treated with Rydapt (midostaurin) in culture (PMID: 31270078). 31270078
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). 23392356
KIT D816V hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). 31309543
Unknown unknown mast-cell leukemia not applicable Midostaurin FDA approved Actionable In a Phase II trial that supported FDA approval, Rydapt (midostaurin) treatment resulted in an overall response rate of 60% (53/89), a median overall survival of 28.7 months, and a median progression-free survival of 14.1 months in patients with systemic mastocytosis including aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast-cell leukemia (PMID: 27355533; NCT00782067). detail... 27355533
KIT exon 11 del gastrointestinal stromal tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and proliferation of gastrointestinal stromal tumor cells harboring KIT exon 11 deletion in culture (PMID: 31085175). 31085175
KIT S476I mast-cell leukemia predicted - sensitive Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) decreased proliferation of patient-derived neoplastic mast cells harboring KIT S476I in culture (PMID: 25209843). 25209843
ETV6 - NTRK3 cancer sensitive Midostaurin Preclinical Actionable In a preclinical study, the broad spectrum kinase inhibitor midostaurin inhibited growth of cells dependent on the fusion protein ETV6-NTRK3, reducing ETV6-NTRK3 kinase activity and downstream signaling and inducing apoptosis (PMID: 23131561). 23131561
KIT D816Y mast cell neoplasm predicted - sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of mouse mastocytoma cells harboring KIT D814Y (corresponds to D816Y in human) in culture (PMID: 31085175). 31085175
CBL Q365_E366insSK FLT3 pos hematologic cancer sensitive Midostaurin Preclinical - Cell line xenograft Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Q365_E366insSK (PMID: 31943762). 31943762
FLT3 Y572C Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3 phosphorylation of ERK1/2 and reduced cell growth in transformed cells expressing FLT3 Y572C in culture (PMID: 18068628). 18068628
FLT3 exon 14 ins acute myeloid leukemia conflicting Midostaurin Preclinical - Cell culture Actionable In a preclinical study, co-culturing human stromal cells with an acute myeloid cell line harboring a FLT3 internal tandem duplication (ITD) demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia conflicting Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
CBL Q365_E366insSK FLT3 wild-type hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). 31309543
KIT D816V Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078). 31270078
KIT Y672C KIT D816V Advanced Solid Tumor decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT Y672C demonstrated a decreased response compared to cells expressing KIT D816V alone when treated with Rydapt (midostaurin) in culture (PMID: 31270078). 31270078
FLT3 exon 14 ins FLT3 N676D Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and N676D were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). 23392356
FLT3 D835Y hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
KIT exon 11 del KIT T670I gastrointestinal stromal tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). 31085175
FLT3 exon 14 ins FLT3 N676T Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 N676T were resistant to treatment with Rydapt (midostaurin) in culture (Blood (2019) 134 (Supplement_1): 2672). detail...
Unknown unknown Advanced Solid Tumor not applicable Midostaurin Phase I Actionable In a Phase I trial, Rydapt (midostaurin) demonstrated safety in patients with advanced solid tumors (PMID: 11230495). 11230495
FLT3 V592G Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3-induced phosphorylation of ERK1/2 and reduced growth of transformed cells expressing FLT3 V592G in culture (PMID: 18068628). 18068628

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Clinical Trial Phase Therapies Title Recruitment Status
NCT01282502 Phase I Midostaurin Midostaurin (PKC412) for Locally Advanced Rectal Cancer Completed
NCT00866281 Phase Ib/II Midostaurin A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia Terminated
NCT03114228 Expanded access Midostaurin An Expanded Treatment Protocol (ETP) of Midostaurin (PKC412) in Patients 18 Years of Age or Older With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia (AML) No longer available
NCT03836209 Phase II Cytarabine + Daunorubicin + Gilteritinib Cytarabine + Daunorubicin + Midostaurin Cytarabine Midostaurin Randomized Trial of Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia Recruiting
NCT03591510 Phase II Cytarabine Cytarabine + Etoposide Cytarabine + Mitoxantrone Cytarabine + Fludarabine + Idarubicin Cytarabine + Daunorubicin + Fludarabine Cytarabine + Daunoxome + Fludarabine Midostaurin A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML Suspended
NCT01883362 Phase II Midostaurin Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML Completed
NCT02624570 Phase I Midostaurin Midostaurin Access Program for Newly Diagnosed FLT3 (ITD or TKD) Mutated AML Adult Patients Eligible for Standard Induction and Consolidation Chemotherapy. No longer available
NCT02115295 Phase II Cladribine + Cytarabine + Idarubicin Midostaurin Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With Acute Myeloid Leukemia (AML), High Risk Myelodysplastic Syndrome (HR MDS) or Myeloid Blast Phase of Chronic Myeloid Leukemia (CML) Recruiting
NCT02756962 Phase II Midostaurin Cytarabine Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance Recruiting
NCT02723435 Phase II Midostaurin Midostaurin in Treating Older Patients With Mutated Acute Myeloid Leukemia Post-Transplant Withdrawn
NCT03900949 Phase I Midostaurin Cytarabine Cytarabine + Gemtuzumab ozogamicin Cytarabine + Daunorubicin + Gemtuzumab ozogamicin Testing the Combination of Standard Induction Therapy With Gemtuzumab Ozogamicin and Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia Recruiting


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