Molecular Profile Detail

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Profile Name IDH2 R172K
Gene Variant Detail

IDH2 R172K (gain of function)

Relevant Treatment Approaches IDH Inhibitor (Pan) IDH2 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH2 R172K acute myeloid leukemia sensitive IDH2 Inhibitor Enasidenib Preclinical - Patient cell culture Actionable In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels and induced differentiation of leukemic blasts from acute myeloid leukemia (AML) patients harboring IDH2 R172K in culture (PMID: 28193778). 28193778
IDH2 R172K glioblastoma predicted - sensitive IDH2 Inhibitor Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a glioblastoma cell line expressing IDH2 R172K in culture (PMID: 28193778). 28193778
IDH2 R172K colorectal cancer predicted - sensitive IDH2 Inhibitor Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a colorectal carcinoma cell line expressing IDH2 R172K in culture (PMID: 28193778). 28193778
IDH2 R172K acute myeloid leukemia sensitive IDH2 Inhibitor Enasidenib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172K is on the companion diagnostic. detail... detail... 28588020
IDH2 R172K high grade glioma sensitive IDH2 Inhibitor TQ05310 Preclinical - Cell culture Actionable In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in a glioma cell line expressing IDH2 R172K in culture (PMID: 31361380). 31361380
IDH2 R172K acute myeloid leukemia sensitive IDH2 Inhibitor TQ05310 Preclinical - Cell culture Actionable In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in an acute myeloid leukemia cell line expressing IDH2 R172K in culture (PMID: 31361380). 31361380
IDH2 R172K acute myeloid leukemia predicted - sensitive IDH2 Inhibitor TQB3455 Case Reports/Case Series Actionable In a Phase I trial, TQB3455 treatment was well tolerated in patients with acute myeloid leukemia harboring IDH2 mutations, and resulted in an objective response rate (ORR) of 40.63% (13/32, 12 complete remission (CR) or CR with incomplete hematological recovery, 1 partial remission), with an ORR of 66.67%, and a CR rate of 41.67% in patients harboring IDH2 R172K (n=14) (Blood (2022) 140 (Supplement 1): 9082-9083). detail...
IDH2 R172K hematologic cancer predicted - sensitive IDH2 Inhibitor SH1573 Preclinical - Biochemical Actionable In a preclinical study, SH1573 inhibited the activity of IDH2 R172K in an in vitro assay (PMID: 34221866). 34221866
IDH2 R172K Advanced Solid Tumor predicted - sensitive IDH Inhibitor (Pan) HMPL-306 Preclinical - Biochemical Actionable In a preclinical study, HMPL-306 inhibited the enzymatic activity of IDH2 R172K in a fluorescence-based assay (Cancer Res (2023) 83 (7_Supplement): 543). detail...
IDH2 R172K acute myeloid leukemia predicted - sensitive IDH2 Inhibitor Enasidenib + Venetoclax Phase Ib/II Actionable In a Phase Ib/II trial, Idhifa (enasidenib) plus Venclexta (venetoclax) was well tolerated and demonstrated activity in relapsed or refractory acute myeloid leukemia patients harboring IDH2 R140Q (15/27) or IDH2 R172K/W (12/27), resulting in an overall response rate (ORR) of 70% (16/23), with complete remission (CR) in 57% (13/23) of evaluable patients, and an ORR of 83% (10/12) and a CR rate of 67% (8/12) in patients harboring IDH2 R172K or IDH2 R172W (Blood (2023) 142 (Supplement 1): 159; NCT04092179). detail...