Molecular Profile |
Indication/Tumor Type |
Response Type |
Therapy Name |
Approval Status |
Evidence Type |
Efficacy Evidence |
References |
IDH1 R132X
|
acute myeloid leukemia
|
predicted - sensitive
|
CG-806
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, patient-derived acute myeloid leukemia cells harboring IDH1 R132X mutations demonstrated increased sensitivity to CG-806 compared to wild-type cells in culture (Proceedings of the American Association for Cancer Research, Vol 60, Mar 2019, Abstract #1323).
|
detail...
|
IDH1 R132X
|
acute myeloid leukemia
|
sensitive
|
IDH305
|
Phase I |
Actionable |
In a Phase I trial, IDH305 treatment resulted in objective response in 33% (7/21) of acute myeloid leukemia patients harboring IDH1 R132 mutations, including complete remission in 3 (14%) and partial remission in 4 (19%) patients (Blood 2016 128 (22):1073).
|
detail...
|
IDH1 R132X
|
low grade glioma
|
predicted - sensitive
|
Ivosidenib
|
Phase I |
Actionable |
In a Phase I trial, low grade glioma patients with an IDH1 mutation (n=66; R132H=57, R132C/G/S=1 each, R132X=5) treated with Tibsovo (ivosidenib) demonstrated an overall response rate of 2.9% (1/35, 1 partial response) and stable disease in 85.7% (30/35) of patients with a non-enhancing glioma versus no responses and stable disease in 45.2% (14/31) of patients with an enhancing glioma, and led to a median progression-free survival of 13.6 months and 1.4 months, respectively (PMID: 32530764; NCT02073994).
|
32530764
|
IDH1 R132X
|
acute myeloid leukemia
|
no benefit
|
BAY1436032
|
Phase I |
Actionable |
In a Phase I trial, treatment with BAY1436032 in acute myeloid leukemia patients harboring an IDH1 R132X mutation demonstrated safety and resulted in an overall response rate of 15% (4/27), including one complete remission, one partial remission, and morphologic leukemia-free state in two patients, stable disease in 67% (18/27), and a median overall survival of 6.6 months, however, due to low response rates for all doses, further clinical development was not supported (PMID: 32733012; NCT03127735).
|
32733012
|
IDH1 mutant
|
acute myeloid leukemia
|
predicted - sensitive
|
Daunorubicin + Talazoparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, the combination therapy of Talzenna (talazoparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH1 mutation, demonstrating decreased colony formation in culture (PMID: 29339439).
|
29339439
|
IDH1 mutant
|
acute myeloid leukemia
|
predicted - sensitive
|
Olaparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH1 mutation were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased colony formation (PMID: 29339439).
|
29339439
|
IDH1 mutant
|
acute myeloid leukemia
|
predicted - sensitive
|
LY3410738
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, LY3410738 reversed mutant IDH1-induced differentiation block in patient-derived acute myeloid leukemia (AML) cells, inhibited 2-HG production, induced differentiation, and eliminated AML cells in patient-derived orthotopic animal models of IDH1-mutant AML (AACR 2019 Annual Meeting, Abstract LB-274).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
predicted - sensitive
|
Talazoparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH1 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439).
|
29339439
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Venetoclax
|
Guideline |
Actionable |
Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Decitabine
|
Guideline |
Actionable |
Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).
|
detail...
|
IDH1 mutant
|
glioblastoma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of secondary grade IV glioblastomas (NCCN.org).
|
detail...
|
IDH1 mutant
|
glioblastoma
|
not applicable
|
N/A
|
Clinical Study |
Prognostic |
In multiple clinical studies, including two meta-analyses, IDH1 mutations were associated with a greater overall survival and progression-free survival in patients with glioblastoma (PMID: 23904262, PMID: 26945349, PMID: 20560678).
|
20560678
23904262
26945349
|
IDH1 mutant
|
anaplastic astrocytoma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Venetoclax
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 72% (13/18) of patients with acute myeloid leukemia harboring IDH1 or IDH2 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Cytarabine + Venetoclax
|
Guideline |
Actionable |
Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
predicted - sensitive
|
Venetoclax
|
Phase II |
Actionable |
In a Phase II trial, 33% (4/12) of acute myeloid leukemia patients harboring either IDH1 or IDH2 mutations responded to treatment with Venclexta (venetoclax), demonstrating a complete response or complete response with incomplete blood count recovery (PMID: 27520294).
|
27520294
|
IDH1 mutant
|
chondrosarcoma
|
resistant
|
Dasatinib
|
Preclinical |
Actionable |
In a preclinical study, chondrosarcoma cells harboring IDH1 mutations were resistant to Sprycel (dasatinib) in culture (PMID: 27231123).
|
27231123
|
IDH1 mutant
|
myeloid neoplasm
|
predicted - sensitive
|
Ivosidenib + Venetoclax
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, Tibsovo (ivosidenib) and Venclexta (venetoclax) combination therapy demonstrated safety and preliminary efficacy in patients with advanced myeloid malignancies harboring IDH1 mutations, resulted in an overall response rate of 67% (4/6) and 100% (6/6) at 400 mg and 800 mg doses, respectively (EMJ Hematol. 2020;8(1):50-53; NCT03471260).
|
detail...
|
IDH1 mutant
|
glioblastoma
|
predicted - sensitive
|
Bevacizumab + Lomustine
|
Phase II |
Actionable |
In a retrospective analysis of a Phase II trial, IDH1 mutation correlated with favorable overall survival in recurrent glioblastoma patients treated with a combination of Avastin (bevacizumab) and Lomustine (PMID: 26762204).
|
26762204
|
IDH1 mutant
|
high grade glioma
|
not applicable
|
N/A
|
Guideline |
Prognostic |
IDH1 mutations are associated with a favorable prognosis in patients with glioma, and are associated with a survival benefit for patients treated with radiation or alkylator therapy (NCCN.org).
|
detail...
|
IDH1 mutant
|
high grade glioma
|
not applicable
|
N/A
|
Clinical Study |
Prognostic |
In multiple clinical studies, including two meta-analyses, IDH1 mutations were associated with improved overall survival and progression free survival in patients with gliomas (PMID: 23817809, PMID: 26220714, PMID: 23894344).
|
23894344
23817809
26220714
|
IDH1 mutant
|
high grade glioma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of gliomas (PMID: 23041832, PMID: 19755387, PMID: 19915484; NCCN.org).
|
detail...
23041832
19755387
19915484
|
IDH1 mutant
|
oligodendroglioma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org).
|
detail...
|
IDH1 mutant
|
myelofibrosis
|
not applicable
|
N/A
|
Guideline |
Prognostic |
IDH1 mutations are associated with inferior leukemia-free survival in patients with myelofibrosis (NCCN.org).
|
detail...
|
IDH1 mutant
|
myelofibrosis
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org).
|
detail...
|
IDH1 mutant
|
polycythemia vera
|
not applicable
|
N/A
|
Guideline |
Prognostic |
IDH1 mutations are associated with inferior overall survival in patients with polycythemia vera (NCCN.org).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
predicted - sensitive
|
Daunorubicin + Olaparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, the combination therapy of Lynparza (olaparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH1 mutation, demonstrating decreased colony formation in culture (PMID: 29339439).
|
29339439
|
IDH1 mutant
|
myeloid neoplasm
|
predicted - sensitive
|
Azacitidine + Ivosidenib + Venetoclax
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) and Venclexta (venetoclax) demonstrated safety and preliminary efficacy in patients with advanced myeloid malignancies harboring IDH1 mutations, resulted in an overall response rate of 100% (8/8) (EMJ Hematol. 2020;8(1):50-53; NCT03471260).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacytidine) combination therapy significantly improved event-free survival (HR 0.33, p=0.002) and median overall survival (24.0 vs 7.9 mo, HR 0.44, p=0.001) compared to Vidaza (azacytidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248).
|
detail...
35443108
detail...
|
IDH1 mutant
|
angioimmunoblastic T-cell lymphoma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org).
|
detail...
|
IDH1 mutant
|
high grade glioma
|
predicted - sensitive
|
AG-881
|
Phase I |
Actionable |
In a Phase I trial, Vorasidenib (AG-881) treatment resulted in an objective response in 13.6% (3/21, 1 partial response, 2 minor response) and stable disease in 77.3% (17/21) of patients with recurrent or progressive non-enhancing glioma harboring mutations in IDH1 (n=20) or IDH2 (n=1), with 60.5% of the patients remained progression-free and alive at 24 months (J Clin Oncol 38: 2020 (suppl; abstr 2504); NCT02481154).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839).
|
detail...
detail...
29860938
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Decitabine + Venetoclax
|
Guideline |
Actionable |
Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).
|
detail...
|
IDH1 mutant
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
Phase I |
Actionable |
In a Phase I trial, AG-120 treatment resulted in partial response in 6% (4/72) and stable disease in 56% (40/72) of cholangiocarcinoma patients harboring IDH1 mutations (Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4015-4015; NCT02073994).
|
detail...
|
IDH1 mutant
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857).
|
detail...
detail...
32416072
|
IDH1 mutant
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) is included in guidelines as subsequent therapy for cholangiocarcinoma patients harboring IDH1 mutations (NCCN.org).
|
detail...
|
IDH1 mutant
|
high grade glioma
|
no benefit
|
Durvalumab + Olaparib
|
Phase II |
Actionable |
In a Phase II trial, combination therapy with Lynparza (olaparib) and Imfinzi (durvalumab) was well tolerated, but lacked antitumor activity in glioma patients with IDH1 (8/9) or IDH2 (1/9) mutations, and led to an objective response in one patient with glioblastoma, stable disease as per RECIST but clinical deterioration in two patients, and progressive disease in 6/9 (67%) patients, with a median progression free survival of 2.5 mo (J Clin Oncol 39, no. 15_suppl (May 20, 2021) abstr e14026); NCT03991832).
|
detail...
|
IDH1 mutant
|
malignant astrocytoma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org).
|
detail...
|
IDH1 mutant
|
acute myeloid leukemia
|
not applicable
|
N/A
|
Clinical Study |
Prognostic |
In two meta-analyses, IDH1 mutations were associated with a worse overall survival in patients with acute myeloid leukemia (PMID: 22616558, PMID: 23226625).
|
22616558
23226625
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Azacitidine
|
Guideline |
Actionable |
Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).
|
detail...
|
IDH1 mutant
|
lung adenocarcinoma
|
resistant
|
Dasatinib
|
Preclinical |
Actionable |
In a preclinical study, lung adenocarcinoma cells harboring IDH1 mutations were resistant to Sprycel (dasatinib) in culture (PMID: 27231123).
|
27231123
|