Therapy Detail

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Therapy Name Midostaurin + Tofacitinib
Synonyms
Therapy Description

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Midostaurin Rydapt PKC412|CGP 41251 CSF1R Inhibitor 26 FLT3 Inhibitor 60 KIT Inhibitor 53 PKC alpha Inhibitor 6 PKC beta Inhibitor 6 PKC Inhibitor (Pan) 11 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).
Tofacitinib Xeljanz Tasocitinib|CP-690550|CP-690,550 JAK Inhibitor (Pan) - ATP competitive 3 Xeljanz (tofacitinib) is a pan-JAK inhibitor, which decreases downstream signaling and potentially leads to reduced tumor cell growth (PMID: 26300391, PMID: 21106989). Xeljanz (tofacitinib) is FDA approved for rheumatoid arthritis (FDA.gov).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins JAK1 R724H JAK3 A573V hematologic cancer sensitive Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 S703I hematologic cancer sensitive Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK2 V617F hematologic cancer decreased response Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F demonstrated a decreased response to treatment with the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) compared to cells expressing a FLT3-ITD mutation and activating mutations of JAK1 or JAK3 in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries


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