Therapy Detail

Therapy Name Midostaurin
Synonym
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 50 KIT Inhibitor 50 PKC alpha Inhibitor 6 PKC beta Inhibitor 6 PKC Inhibitor (Pan) 10 VEGFR2 Inhibitor 34 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).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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
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). 27355533
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 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...
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 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
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...
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
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
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
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
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
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 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
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 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
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
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...
Clinical Trial Phase Therapies Title Recruitment Status
NCT00866281 Phase Ib/II Midostaurin A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia Terminated
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 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
NCT01282502 Phase I Midostaurin Midostaurin (PKC412) for Locally Advanced Rectal Cancer Completed
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
NCT02756962 Phase II Midostaurin Cytarabine Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance Recruiting
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. 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
NCT01883362 Phase II Midostaurin Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML Completed