|
IDH1 wild-type
|
high grade glioma
|
not applicable
|
N/A
|
Guideline |
Risk Factor |
IDH1 wild-type is associated with increased risk of aggressive disease in patients with grade II or III infiltrative gliomas (NCCN.org).
|
detail...
|
|
IDH1 wild-type
|
IDH-wildtype glioblastoma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
Wild-type IDH1 aids in the diagnosis of glioblastoma (NCCN.org).
|
detail...
|
|
IDH1 wild-type PTEN mut
|
glioblastoma
|
resistant
|
Nivolumab
|
Clinical Study - Cohort |
Actionable |
In a retrospective analysis, PTEN mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who did not respond to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who responded (odds ratio=0.85, p=0.0063), with 23 PTEN mutations identified in 32 non-responders and 3 in 13 responders (PMID: 30742119).
|
30742119
|
|
IDH1 wild-type PTEN mut
|
glioblastoma
|
resistant
|
Pembrolizumab
|
Clinical Study - Cohort |
Actionable |
In a retrospective analysis, PTEN mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who did not respond to anti-PD-1 therapy, with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who responded (odds ratio=0.85, p=0.0063), with 23 PTEN mutations identified in 32 non-responders and 3 in 13 responders (PMID: 30742119).
|
30742119
|
|
BRAF mut IDH1 wild-type
|
glioblastoma
|
predicted - sensitive
|
Nivolumab
|
Clinical Study - Cohort |
Actionable |
In a retrospective analysis, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119).
|
30742119
|
|
BRAF mut IDH1 wild-type
|
glioblastoma
|
predicted - sensitive
|
Pembrolizumab
|
Clinical Study - Cohort |
Actionable |
In a retrospective analysis, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119).
|
30742119
|
|
FLT3 D835Y IDH1 wild-type
|
hematologic cancer
|
sensitive
|
Crenolanib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Crenolanib (CP-868596) decreased proliferation of transformed cells expressing FLT3 D835Y and IDH1 wild-type (PMID: 30651561).
|
30651561
|
|
FLT3 D835Y IDH1 wild-type
|
hematologic cancer
|
resistant
|
AGI-5198
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AGI-5198 treatment did not decrease proliferation of transformed cells expressing FLT3 D835Y and IDH1 wild-type in culture (PMID: 30651561).
|
30651561
|
|
FLT3 D835Y IDH1 wild-type
|
hematologic cancer
|
sensitive
|
AGI-5198 + Crenolanib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of Crenolanib (CP-868596) and AGI-5198 synergistically decreased proliferation of transformed cells expressing FLT3 D835Y and IDH1 wild-type in culture (PMID: 30651561).
|
30651561
|
|
IDH1 R132H
|
oligodendroglioma
|
sensitive
|
Decitabine
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, Dacogen (decitabine) decreased colony formation and tumor growth in patient derived xenograft (PDX) models of patient derived oligodendroglioma cells with IDH1 R132H mutations and co-deletion of 1p and 19q (PMID: 24077826).
|
24077826
|
|
IDH1 R132H
|
anaplastic astrocytoma
|
sensitive
|
Azacitidine
|
Preclinical |
Actionable |
In a preclinical study, long-term treatment with Vidaza (azacitidine) resulted in increased cellular differentiation, decreased proliferation, and tumor regression in a patient-derived xenograft (PDX) model of anaplastic astrocytoma harboring IDH1 R132H (PMID: 24077805).
|
24077805
|
|
IDH1 R132H
|
colon carcinoma
|
sensitive
|
Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, colon carcinoma cells over expressing IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
Talazoparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, patient-derived glioma cells harboring IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Talzenna (talazoparib) treatment inhibited viability of immortalized astrocytes expressing IDH1 R132H in culture (PMID: 34118569).
|
34118569
|
|
IDH1 R132H
|
colorectal cancer
|
predicted - sensitive
|
Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, colorectal cancer cells harboring IDH1 R132H were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439).
|
29339439
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Niraparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Zejula (niraparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
colon carcinoma
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, colon carcinoma cells over expressing IDH1 R132H demonstrated increased sensitivity to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
high grade glioma
|
predicted - sensitive
|
Olaparib
|
Phase II |
Actionable |
In a Phase II trial (OLAGLI), Lynparza (olaparib) therapy was well tolerated in high grade glioma patients harboring IDH1 R132 (32/35) or other IDH mutations (3/35), and led to a partial response in 5% (2/35) and stable disease in 37% (14/35) of 35 evaluable patients, median progression-free survival (PFS) of 2.3 mo, median overall survival of 15.9 mo, a median duration of response of 9 mo, and a 6-mo PFS of 31% (11/35) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 2007-2007; NCT03561870).
|
detail...
|
|
IDH1 R132H
|
high grade glioma
|
predicted - sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment inhibited viability of a glioma cell line expressing IDH1 R132H in culture (PMID: 34118569).
|
34118569
|
|
IDH1 R132H
|
colorectal cancer
|
predicted - sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, colorectal cancer cells harboring IDH1 R132H were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased colony formation (PMID: 29339439).
|
29339439
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Rucaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Rubraca (rucaparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
colorectal cancer
|
sensitive
|
Metformin
|
Preclinical |
Actionable |
In a preclinical study, colorectal carcinoma cells expressing IDH1 R132H were sensitive to Glucophage (metformin), resulting in decreased cell proliferation in culture (PMID: 26363012).
|
26363012
|
|
IDH1 R132H
|
glioblastoma
|
resistant
|
Valproic acid
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, glioblastoma cells expressing IDH1 R132H were resistant to treatment with Valproic Acid in culture, demonstrating increased cell viability (PMID: 31151327).
|
31151327
|
|
IDH1 R132H
|
glioblastoma
|
resistant
|
Vorinostat
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, glioblastoma cells expressing IDH1 R132H were resistant to treatment with Zolinza (vorinostat) in culture, demonstrating increased cell viability (PMID: 31151327).
|
31151327
|
|
IDH1 R132H
|
high grade glioma
|
decreased response
|
Panobinostat
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, mouse glioma cells expressing IDH1 R132H were less sensitive to Farydak (panobinostat) compared to IDH1 wild-type cells in culture (PMID: 38334611).
|
38334611
|
|
IDH1 R132H
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - On 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...
32416072
detail...
|
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On 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).
|
29860938
detail...
detail...
|
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
29860938
detail...
detail...
|
|
IDH1 R132H
|
myelodysplastic syndrome
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) was tolerated and resulted in a complete response (CR) in 44% (7/16), partial response (PR) in 6% (1/16), and marrow CR in 31% (5/16) of patients with relapsed or refractory myelodysplastic syndrome harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a hematologic improvement in >/=1 lineages achieved by 69% (11/16) of patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 7053; NCT02074839).
|
detail...
detail...
detail...
|
|
IDH1 R132H
|
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 R132H
|
high grade glioma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 R132H is diagnostic and aids in the diagnosis of gliomas (NCCN.org).
|
detail...
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
AGI-5198
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, AGI-5198 inhibited growth of a glioma cell line harboring IDH1 R132H in culture and in xenograft models (PMID: 23558169).
|
23558169
|
|
IDH1 R132H
|
glioblastoma
|
resistant
|
Trichostatin A
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, glioblastoma cells expressing IDH1 R132H were resistant to treatment with Trichostatin (TSA) in culture, demonstrating decreased apoptotic activity and increased cell viability (PMID: 31151327).
|
31151327
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Berzosertib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, transformed cells expressing IDH1 R132H demonstrated increased sensitivity to Berzosertib (VX-970)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Ceralasertib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, treatment with Ceralasertib (AZD6738) resulted in decreased survival in cell lines expressing IDH1 R132H in culture (PMID: 34027408).
|
34027408
|
|
IDH1 R132H
|
high grade glioma
|
predicted - sensitive
|
Vorasidenib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Voranigo (vorasidenib) treatment decreased brain tumor 2HG levels in an orthotopic glioma cell line xenograft model harboring IDH1 R132H (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126).
|
detail...
|
|
IDH1 R132H
|
glioblastoma
|
sensitive
|
Temozolomide + Vandetanib
|
Phase II |
Actionable |
In a Phase II trial, Caprelsa (vandetanib), in combination with Temodar (temozolomide) and radiation therapy, demonstrated a significant increase in PFS and OS in glioblastoma patients harboring IDH1 R132H compared to glioblastoma patients without IDH1 R132H (PMID: 25910950).
|
25910950
|
|
IDH1 R132H
|
colorectal cancer
|
resistant
|
AGI-5198 + Metformin
|
Preclinical |
Actionable |
In a preclinical study, colorectal cancer cells harboring IDH1 R132H demonstrated increased cell proliferation when treated with a combination of Glucophage (metformin) and AGI-5198 (PMID: 26363012).
|
26363012
|
|
IDH1 R132H
|
colorectal cancer
|
resistant
|
AGI-5198 + Radiotherapy
|
Preclinical |
Actionable |
In a preclinical study, colorectal cancer cells expressing IDH1 R132H were resistant to radiotherapy when treated with AGI-5198 (PMID: 26363012).
|
26363012
|
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
Phase Ib/II |
Actionable |
In a Phase Ib trial, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination treatment demonstrated a favorable safety profile and resulted in an objective response rate (ORR) of 78.3% (18/23, 14 complete remission) and a 12-month overall survival probability of 82% in patients with newly diagnosed acute myeloid leukemia harboring IDH1 R132H (n=4), R132C (n=16), or R132L (n=3) mutations (PMID: 33119479; NCT02677922).
|
33119479
|
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) 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 (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248).
|
35443108
detail...
detail...
|
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
Olutasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (Study 2102-HEM-101) that supported FDA approval, Rezlidhia (olutasidenib) treatment resulted in an objective response rate of 46% (57/123, 37 complete remission (CR), 4 CR with partial hematologic recovery, 14 CR with incomplete recovery, 1 morphologic leukemia-free state, 1 partial response) in patients with relapsed/refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132H/C/G/L/S) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574).
|
detail...
detail...
detail...
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Ceralasertib + Olaparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell survival compared to Ceralasterib (AZD6738) alone in cells expressing IDH1 R132H in culture, and a longer delay in tumor growth in cell line xenograft models (PMID: 34027408).
|
34027408
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
BPTES
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, a glioma cell line expressing IDH1 R132H demonstrated increased sensitivity to growth inhibition by BPTES compared to a cell line expressing wild-type IDH1 in culture (PMID: 21045145).
|
21045145
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Cisplatin + Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Talzenna (talazoparib) and Cisplatin synergistically inhibited growth of transformed cells over expressing IDH1 R132H in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
decreased response
|
AGI-5198 + Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AGI-5198 reverted the sensitivity of transformed cells over expressing IDH1 R132H to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132H
|
acute myeloid leukemia
|
sensitive
|
BAY1436032
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels, and inhibited growth and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132H in culture (PMID: 28232670).
|
28232670
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Elimusertib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, treatment with Elimusertib (BAY1895344) resulted in decreased survival in cell lines expressing IDH1 R132H in culture (PMID: 34027408).
|
34027408
|
|
IDH1 R132H
|
glioblastoma
|
sensitive
|
DS-1001b
|
Preclinical - Pdx |
Actionable |
In a preclinical study, treatment with DS-1001b inhibited subcutaneous and intracranial tumor growth in a patient-derived xenograft (PDX) model of glioblastoma harboring IDH1 R132H, and also demonstrated reduced levels of the oncometabolite 2-hydroxyglutarate (2-HG) within tumors and plasma and increased expression of the astrocyte differentiation marker glial fibrillary acidic protein in tumor cells (PMID: 31727689).
|
31727689
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
predicted - sensitive
|
DS-1001b
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, DS-1001b inhibited IDH1 R132H enzymatic activity in an in vitro assay, and inhibited production of the oncometabolite 2-hydroxyglutarate (2-HG) in transformed human cells expressing IDH1 R132H in culture (PMID: 31727689).
|
31727689
|
|
IDH1 R132H
|
malignant astrocytoma
|
predicted - sensitive
|
IDH1 R132H peptide vaccine
|
Phase I |
Actionable |
In a Phase I trial (NOA-16), treatment with IDH1 R132H peptide vaccine demonstrated safety in patients with malignant astrocytoma harboring IDH1 R132H and led to stable disease in 87.5% (28/32) of patients (J Clin Oncol 36, no. 15_suppl (May 20, 2018) 2001; NCT02454634).
|
detail...
|
|
IDH1 R132H
|
glioblastoma
|
predicted - sensitive
|
AGI-5198 + Trichostatin A
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the addition of AGI-5198 treatment in glioblastoma cells expressing IDH1 R132H led to decreased resistance to Trichostatin (TSA) treatment in culture, resulting in reduced cell viability (PMID: 31151327).
|
31151327
|
|
IDH1 R132H
|
glioblastoma
|
predicted - sensitive
|
AGI-5198 + Vorinostat
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the addition of AGI-5198 treatment in glioblastoma cells expressing IDH1 R132H led to decreased resistance to Zolinza (vorinostat) treatment in culture, resulting in reduced cell viability (PMID: 31151327).
|
31151327
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
Olaparib + Radiotherapy
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, treatment with Lynparza (olaparib) enhanced the sensitivity of immortalized astrocytes expressing IDH1 R132H to radiation therapy in culture, resulting in increased cell death and decreased colony formation compared to radiation therapy alone (PMID: 32494639).
|
32494639
|
|
IDH1 R132H
|
intrahepatic cholangiocarcinoma
|
sensitive
|
Olaparib + Radiotherapy
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, treatment with Lynparza (olaparib) enhanced the sensitivity of an intrahepatic cholangiocarcinoma cell line expressing IDH1 R132H to radiation therapy, resulting in decreased survival in culture and delayed tumor growth and increased survival compared to radiation therapy alone in a cell line xenograft model, with a median overall survival of 60 days vs 47 days, respectively (PMID: 32494639).
|
32494639
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
predicted - sensitive
|
HMPL-306
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, HMPL-306 inhibited the enzymatic activity of IDH1 R132H in a fluorescence-based assay (Cancer Res (2023) 83 (7_Supplement): 543).
|
detail...
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Elimusertib + Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of Lynparza (olaparib) and Elimusertib (BAY1895344) resulted in a greater decrease in cell survival compared to BAY1895344 alone in cells expressing IDH1 R132H in culture (PMID: 34027408).
|
34027408
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Ceralasertib + Niraparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of Zejula (niraparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell viability compared to Ceralasertib (AZD6738) alone in cells expressing IDH1 R132H in culture (PMID: 34027408).
|
34027408
|
|
IDH1 R132H
|
Advanced Solid Tumor
|
sensitive
|
Ceralasertib + Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of Talzenna (talazoparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell viability compared to Ceralasertib (AZD6738) alone in cells expressing IDH1 R132H in culture (PMID: 34027408).
|
34027408
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
Radiotherapy + Veliparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, treatment with Veliparib (ABT-888) enhanced sensitivity to radiation therapy in immortalized astrocytes expressing IDH1 R132H in culture, resulting in greater decreased colony formation, and in a glioma cell line xenograft model, resulting in both increased tumor regression and survival compared to radiation therapy alone, with a median overall survival of 66 days vs 22 days, respectively (PMID: 32494639).
|
32494639
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
Pamiparib + Radiotherapy
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, treatment with Pamiparib (BGB-290) enhanced the sensitivity of a glioma cell line expressing IDH1 R132H to radiation therapy, resulting in a reduction in tumor volume and increased survival compared to radiation therapy alone in a cell line xenograft model (PMID: 32494639).
|
32494639
|
|
IDH1 R132H
|
high grade glioma
|
sensitive
|
Panobinostat + Tazemetostat
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, cotreatment with Tazverik (tazemetostat) sensitized mouse glioma cells expressing IDH1 R132H to Farydak (panobinostat) in culture, resulting in synergistic inhibition of cell viability (PMID: 38334611).
|
38334611
|
|
FLT3 D835Y IDH1 R132H
|
hematologic cancer
|
sensitive
|
Crenolanib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Crenolanib (CP-868596) decreased proliferation of transformed cells expressing FLT3 D835Y and IDH1 R132H in culture (PMID: 30651561).
|
30651561
|
|
FLT3 D835Y IDH1 R132H
|
hematologic cancer
|
resistant
|
AGI-5198
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AGI-5198 treatment did not decrease proliferation of transformed cells expressing FLT3 D835Y and IDH1 R132H in culture (PMID: 30651561).
|
30651561
|
|
FLT3 D835Y IDH1 R132H
|
hematologic cancer
|
sensitive
|
AGI-5198 + Crenolanib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of Crenolanib (CP-868596) and AGI-5198 synergistically decreased proliferation of transformed cells expressing FLT3 D835Y and IDH1 R132H in culture (PMID: 30651561).
|
30651561
|
|
FLT3 exon 14 ins IDH1 R132H
|
hematologic cancer
|
sensitive
|
Crenolanib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Crenolanib (CP-868596) decreased proliferation of transformed cells expressing FLT3-ITD and IDH1 R132H in culture (PMID: 30651561).
|
30651561
|
|
FLT3 exon 14 ins IDH1 R132H
|
hematologic cancer
|
sensitive
|
AGI-5198 + Crenolanib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, transformed cells expressing FLT3-ITD and IDH1 R132H demonstrated increased sensitivity to treatment with the combination of Crenolanib (CP-868596) and AGI-5198 compared to treatment with Crenolanib (CP-868596) alone in culture (PMID: 30651561).
|
30651561
|
|
IDH1 R132H IDH1 D279N
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Tibsovo (ivosidenib) modestly suppressed (R)-2-hydroxyglutarate (R-2HG) production in an acute myeloid leukemia cell line expressing IDH1 R132H and D279N but did not inhibit cytokine-independent growth in culture (PMID: 36056177).
|
36056177
|
|
IDH1 R132H IDH1 D279N
|
acute myeloid leukemia
|
sensitive
|
LY3410738
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, LY3410738 inhibited (R)-2-hydroxyglutarate (R-2HG) production and cytokine-independent growth in an acute myeloid leukemia cell line expressing IDH1 R132H and D279N in culture (PMID: 36056177).
|
36056177
|
|
IDH1 R132H IDH1 S280F
|
leukemia
|
predicted - resistant
|
Ivosidenib
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, Tibsovo (ivosidenib) did not inhibit Idh1 activity and R-2HG production in a leukemia cell line expressing IDH1 R132H and S280F in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 H315D
|
leukemia
|
resistant
|
Ivosidenib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Tibsovo (ivosidenib) did not inhibit Idh1 activity and R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 H315D
|
leukemia
|
predicted - resistant
|
IDH305
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, IDH305 did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 H315D
|
leukemia
|
predicted - resistant
|
Vorasidenib
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, Voranigo (vorasidenib) did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 H315D
|
leukemia
|
predicted - resistant
|
BAY1436032
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, BAY1436032 did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and H315D in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH2 R140Q
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH2 R140Q was identified at progression in 4 patients with acute myeloid leukemia harboring IDH1 R132H who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R132H IDH1 T313I
|
leukemia
|
resistant
|
Ivosidenib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Tibsovo (ivosidenib) did not inhibit Idh1 activity and R-2HG production in a leukemia cell line expressing IDH1 R132H and T313I in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 T313I
|
leukemia
|
predicted - resistant
|
IDH305
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, IDH305 did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and T313I in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 T313I
|
leukemia
|
predicted - resistant
|
Vorasidenib
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, Voranigo (vorasidenib) did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and T313I in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 T313I
|
leukemia
|
predicted - resistant
|
BAY1436032
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, BAY1436032 did not inhibit R-2HG production in a leukemia cell line expressing IDH1 R132H and T313I in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 A410T
|
leukemia
|
predicted - sensitive
|
Ivosidenib
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, Tibsovo (ivosidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH1 R132H and A410T in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132H IDH1 L409V
|
leukemia
|
predicted - sensitive
|
Ivosidenib
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, Tibsovo (ivosidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH1 R132H and L409V in culture (PMID: 36222845).
|
36222845
|
|
IDH1 R132C
|
high grade glioma
|
sensitive
|
Talazoparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, patient-derived glioma cells harboring IDH1 R132C demonstrated increased sensitivity to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132C
|
intrahepatic cholangiocarcinoma
|
sensitive
|
Dasatinib
|
Preclinical |
Actionable |
In a preclinical study, Sprycel (dasatinib) inhibited growth of intrahepatic cholangiocarcinoma cells harboring IDH1 R132C in culture, and suppressed tumor growth in PDX models (PMID: 27231123).
|
27231123
|
|
IDH1 R132C
|
cholangiocarcinoma
|
no benefit
|
Niraparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, cholangiocarcinoma patient-derived xenograft (PDX) cell lines harboring IDH1 R132C were insensitive to Zejula (niraparib) in culture (PMID: 36374558).
|
36374558
|
|
IDH1 R132C
|
sarcoma
|
sensitive
|
Olaparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Lynparza (olaparib) treatment delayed tumor growth in cell line xenograft models of sarcoma harboring IDH1 R132C (PMID: 28148839).
|
28148839
|
|
IDH1 R132C
|
chondrosarcoma
|
predicted - sensitive
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in a partial response with 59% tumor reduction lasting 14 months in one patient and stable disease lasting 7.5 months in one patient out of four patients with chondrosarcoma harboring IDH1 R132C (PMID: 34994649, NCT02576444).
|
34994649
|
|
IDH1 R132C
|
cholangiocarcinoma
|
no benefit
|
Olaparib
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, cholangiocarcinoma patient-derived xenograft (PDX) cell lines harboring IDH1 R132C were insensitive to Lynparza (olaparib) in culture and did not inhibit tumor growth in the patient-derived xenograft (PDX) model (PMID: 36374558).
|
36374558
|
|
IDH1 R132C
|
intrahepatic cholangiocarcinoma
|
sensitive
|
Saracatinib
|
Preclinical |
Actionable |
In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132C demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123).
|
27231123
|
|
IDH1 R132C
|
chondrosarcoma
|
predicted - sensitive
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Tibsovo (ivosidenib) treatment was tolerated, substantially decreased plasma 2-HG levels, and resulted in a median progression-free survival of 5.6 months and stable disease in 52% (11/21) of patients with chondrosarcoma harboring IDH1 mutations, including IDH1 R132C (n=13) (PMID: 32208957; NCT02073994).
|
32208957
|
|
IDH1 R132C
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - On 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 R132C
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On 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...
detail...
29860938
|
|
IDH1 R132C
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
|
IDH1 R132C
|
myelodysplastic syndrome
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) was tolerated and resulted in a complete response (CR) in 44% (7/16), partial response (PR) in 6% (1/16), and marrow CR in 31% (5/16) of patients with relapsed or refractory myelodysplastic syndrome harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a hematologic improvement in >/=1 lineages achieved by 69% (11/16) of patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 7053; NCT02074839).
|
detail...
detail...
detail...
|
|
IDH1 R132C
|
high grade glioma
|
sensitive
|
AGI-5198
|
Preclinical |
Actionable |
In a preclinical study, AGI-5198 inhibited growth and promoted differentiation in glioma cells expressing IDH1 R132C (PMID: 23558169).
|
23558169
|
|
IDH1 R132C
|
cholangiocarcinoma
|
no benefit
|
Pamiparib
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, cholangiocarcinoma patient-derived xenograft (PDX) cell lines harboring IDH1 R132C were insensitive to Pamiparib (BGB-290) in culture and did not inhibit tumor growth in the patient-derived xenograft (PDX) model (PMID: 36374558).
|
36374558
|
|
IDH1 R132C
|
fibrosarcoma
|
predicted - sensitive
|
Vorasidenib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, Voranigo (vorasidenib) treatment decreased tumor 2HG levels in a fibrosarcoma cell line xenograft model harboring IDH1 R132C (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126).
|
detail...
|
|
IDH1 R132C
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
Phase Ib/II |
Actionable |
In a Phase Ib trial, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination treatment demonstrated a favorable safety profile and resulted in an objective response rate (ORR) of 78.3% (18/23, 14 complete remission) and a 12-month overall survival probability of 82% in patients with newly diagnosed acute myeloid leukemia harboring IDH1 R132C (n=14), R132H (n=4), or R132L (n=3) mutations (PMID: 33119479; NCT02677922).
|
33119479
|
|
IDH1 R132C
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) 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 (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248).
|
35443108
detail...
detail...
|
|
IDH1 R132C
|
acute myeloid leukemia
|
sensitive
|
Olutasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (Study 2102-HEM-101) that supported FDA approval, Rezlidhia (olutasidenib) treatment resulted in an objective response rate of 46% (57/123, 37 complete remission (CR), 4 CR with partial hematologic recovery, 14 CR with incomplete recovery, 1 morphologic leukemia-free state, 1 partial response) in patients with relapsed/refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574).
|
detail...
detail...
detail...
|
|
IDH1 R132C
|
fibrosarcoma
|
sensitive
|
Ceralasertib + Olaparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater delay in tumor growth compared to Ceralasertib (AZD6738) alone in fibrosarcoma cell line xenograft models harboring IDH1 R132C (PMID: 34027408).
|
34027408
|
|
IDH1 R132C
|
sarcoma
|
decreased response
|
AGI-5198 + Talazoparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Talzenna (talazoparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132C
|
sarcoma
|
decreased response
|
AGI-5198 + Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839).
|
28148839
|
|
IDH1 R132C
|
acute myeloid leukemia
|
sensitive
|
BAY1436032
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, BAY1436032 decreased R-2HG levels and inhibited growth of primary acute myeloid leukemia (AML) cells harboring IDH1 R132C in culture, and decreased blast number and increased survival of two AML patient-derived xenograft (PDX) models, one which harbored additional alterations in FLT3, NPM1, and NRAS and one which harbored a KMT2A (MLL) alteration (PMID: 28232670).
|
28232670
|
|
IDH1 R132C
|
Advanced Solid Tumor
|
predicted - sensitive
|
DS-1001b
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, DS-1001b inhibited IDH1 R132C enzymatic activity in an in vitro assay, and inhibited production of the oncometabolite 2-hydroxyglutarate (2-HG) in transformed human cells expressing IDH1 R132C in culture (PMID: 31727689).
|
31727689
|
|
IDH1 R132C
|
intrahepatic cholangiocarcinoma
|
sensitive
|
Olaparib + Radiotherapy
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, treatment with Lynparza (olaparib) enhanced the sensitivity of an intrahepatic cholangiocarcinoma cell line harboring IDH1 R132C to radiation therapy in culture, resulting in decreased survival compared to radiation therapy alone (PMID: 32494639).
|
32494639
|
|
IDH1 R132C
|
leukemia
|
sensitive
|
TETi76
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, TETi76 treatment decreased viability of a leukemia cell line expressing IDH1 R132C in culture (PMID: 33681816).
|
33681816
|
|
IDH1 R132C IDH1 S280F
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, a patient with acute myeloid leukemia (AML) harboring IDH1 R132C progressed following an initial response to treatment with Tibsovo (ivosidenib), and was found to have acquired IDH1 S280F (PMID: 33832922).
|
33832922
|
|
IDH1 R132C IDH1 S280F
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a clinical study, IDH1 S280F was identified as an acquired mutation in cis with the original IDH1 R132C in a patient with acute myeloid leukemia (AML), who developed resistance to Tibsovo (ivosidenib) after initial response (PMID: 29950729).
|
29950729
|
|
IDH1 R132C IDH1 S280F
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 S280F was identified at progression in 3 patients with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R132C IDH2 R172K
|
intrahepatic cholangiocarcinoma
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, IDH2 R172K was identified upon progression in a patient with metastatic intrahepatic cholangiocarcinoma harboring IDH1 R132C, along with PIK3CA E545K, who previously responded to Tibsovo (ivosidenib) (PMID: 36056177).
|
36056177
|
|
IDH1 R132C IDH1 D279N
|
intrahepatic cholangiocarcinoma
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, IDH1 D279N was identified upon progression in a patient with metastatic intrahepatic cholangiocarcinoma harboring IDH1 R132C, along with NRAS G13V, who previously responded to Tibsovo (ivosidenib) (PMID: 36056177).
|
36056177
|
|
IDH1 R132C IDH1 D279N IDH2 R140Q
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 D279N and IDH2 R140Q were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 G131A IDH1 R132C
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 G131A was identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R132C IDH1 D279N IDH1 H315D
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 H315D and D279N were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R132C IDH2 R140Q
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH2 R140Q was identified at progression in 5 patients with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R132C IDH1 T313I
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a clinical case study, IDH1 T313I was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH1 R132C upon progression on Tibsovo (ivosidenib) (PMID: 36222845).
|
36222845
|
|
BRAF V600E IDH1 R132C
|
melanoma
|
predicted - sensitive
|
Dabrafenib + Trametinib
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response with an overall survival of 51.1 months and a duration of treatment of 4.1 months in a melanoma patient harboring BRAF V600E and IDH1 R132C (PMID: 39500140).
|
39500140
|
|
BRAF V600E IDH1 R132C
|
lung squamous cell carcinoma
|
predicted - sensitive
|
Dabrafenib + Trametinib
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response with a progression-free survival of 14.8 months, an overall survival of 34.6 months, and a duration of treatment of 14.9 months in a patient with squamous non-small cell lung cancer harboring BRAF V600E and IDH1 R132C (PMID: 39500140).
|
39500140
|
|
IDH1 R132S
|
intrahepatic cholangiocarcinoma
|
sensitive
|
Dasatinib
|
Preclinical |
Actionable |
In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132S demonstrated increased sensitivity to Sprycel (dasatinib) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123).
|
27231123
|
|
IDH1 R132S
|
chondrosarcoma
|
predicted - sensitive
|
Olaparib
|
Case Reports/Case Series |
Actionable |
In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in stable disease lasting 10 months in a patient with chondrosarcoma harboring IDH1 R132S (PMID: 34994649, NCT02576444).
|
34994649
|
|
IDH1 R132S
|
intrahepatic cholangiocarcinoma
|
sensitive
|
Saracatinib
|
Preclinical |
Actionable |
In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132S demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123).
|
27231123
|
|
IDH1 R132S
|
chondrosarcoma
|
predicted - sensitive
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Tibsovo (ivosidenib) treatment was tolerated, substantially decreased plasma 2-HG levels, and resulted in a median progression-free survival of 5.6 months and stable disease in 52% (11/21) of patients with chondrosarcoma harboring IDH1 mutations, including IDH1 R132S (n=1) (PMID: 32208957; NCT02073994).
|
32208957
|
|
IDH1 R132S
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - On 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 R132S
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On 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...
29860938
detail...
|
|
IDH1 R132S
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
|
IDH1 R132S
|
myelodysplastic syndrome
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) was tolerated and resulted in a complete response (CR) in 44% (7/16), partial response (PR) in 6% (1/16), and marrow CR in 31% (5/16) of patients with relapsed or refractory myelodysplastic syndrome harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a hematologic improvement in >/=1 lineages achieved by 69% (11/16) of patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 7053; NCT02074839).
|
detail...
detail...
detail...
|
|
IDH1 R132S
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) 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 (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248).
|
35443108
detail...
detail...
|
|
IDH1 R132S
|
acute myeloid leukemia
|
sensitive
|
Olutasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (Study 2102-HEM-101) that supported FDA approval, Rezlidhia (olutasidenib) treatment resulted in an objective response rate of 46% (57/123, 37 complete remission (CR), 4 CR with partial hematologic recovery, 14 CR with incomplete recovery, 1 morphologic leukemia-free state, 1 partial response) in patients with relapsed/refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132S/C/G/H/L) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574).
|
detail...
detail...
detail...
|
|
IDH1 R132S
|
cholangiocarcinoma
|
sensitive
|
Ceralasertib + Olaparib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell viability compared to Ceralasertib (AZD6738) alone in cholangiocarcinoma cells harboring IDH1 R132S in culture (PMID: 34027408).
|
34027408
|
|
IDH1 R132S
|
acute myeloid leukemia
|
sensitive
|
BAY1436032
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels, and inhibited growth and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132S in culture (PMID: 28232670).
|
28232670
|
|
IDH1 R132S
|
Advanced Solid Tumor
|
predicted - sensitive
|
DS-1001b
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, transformed human cells expressing IDH1 R132S demonstrated sensitivity to DS-1001b in culture, resulting in reduced production of the oncometabolite 2-hydroxyglutarate (2-HG) (PMID: 31727689).
|
31727689
|
|
IDH1 R119P IDH1 R132S
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 R119P was identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132S who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R132L
|
chondrosarcoma
|
predicted - sensitive
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Tibsovo (ivosidenib) treatment was tolerated, substantially decreased plasma 2-HG levels, and resulted in a median progression-free survival of 5.6 months and stable disease in 52% (11/21) of patients with chondrosarcoma harboring IDH1 mutations, including IDH1 R132L (n=1) (PMID: 32208957; NCT02073994).
|
32208957
|
|
IDH1 R132L
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - On 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...
32416072
detail...
|
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On 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).
|
29860938
detail...
detail...
|
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
29860938
detail...
detail...
|
|
IDH1 R132L
|
myelodysplastic syndrome
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) was tolerated and resulted in a complete response (CR) in 44% (7/16), partial response (PR) in 6% (1/16), and marrow CR in 31% (5/16) of patients with relapsed or refractory myelodysplastic syndrome harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a hematologic improvement in >/=1 lineages achieved by 69% (11/16) of patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 7053; NCT02074839).
|
detail...
detail...
detail...
|
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
Phase Ib/II |
Actionable |
In a Phase Ib trial, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination treatment demonstrated a favorable safety profile and resulted in an objective response rate (ORR) of 78.3% (18/23, 14 complete remission) and a 12-month overall survival probability of 82% in patients with newly diagnosed acute myeloid leukemia harboring IDH1 R132L (n=3), R132H (n=4), or R132C (n=16) mutations (PMID: 33119479; NCT02677922).
|
33119479
|
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) 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 (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248).
|
35443108
detail...
detail...
|
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
Olutasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (Study 2102-HEM-101) that supported FDA approval, Rezlidhia (olutasidenib) treatment resulted in an objective response rate of 46% (57/123, 37 complete remission (CR), 4 CR with partial hematologic recovery, 14 CR with incomplete recovery, 1 morphologic leukemia-free state, 1 partial response) in patients with relapsed/refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132L/C/G/H/S) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574).
|
detail...
detail...
detail...
|
|
IDH1 R132L
|
acute myeloid leukemia
|
sensitive
|
BAY1436032
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels, and inhibited growth and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132L in culture (PMID: 28232670).
|
28232670
|
|
IDH1 R132L
|
Advanced Solid Tumor
|
predicted - sensitive
|
DS-1001b
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, transformed human cells expressing IDH1 R132L demonstrated sensitivity to DS-1001b in culture, resulting in reduced production of the oncometabolite 2-hydroxyglutarate (2-HG) (PMID: 31727689).
|
31727689
|
|
IDH1 R119P IDH1 R132L IDH2 R140Q
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 R119P and IDH2 R140Q were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132L who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R132L IDH2 R140Q
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH2 R140Q was identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132L who previously had a response of stable disease with Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
IDH1 R119P IDH1 R132L
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 R119P was identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132L who previously had a response of stable disease with Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
ARID1B Q127_Q131del IDH1 R132L
|
cholangiocarcinoma
|
no benefit
|
Niraparib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, a cholangiocarcinoma patient-derived xenograft (PDX) cell line harboring IDH1 R132L and ARID1B Q127_Q131del was insensitive to Zejula (niraparib) in culture (PMID: 36374558).
|
36374558
|
|
ARID1B Q127_Q131del IDH1 R132L
|
cholangiocarcinoma
|
no benefit
|
Olaparib
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, a cholangiocarcinoma patient-derived xenograft (PDX) cell line harboring IDH1 R132L and ARID1B Q127_Q131del was insensitive to Lynparza (olaparib) in culture and did not inhibit tumor growth in the patient-derived xenograft model (PMID: 36374558).
|
36374558
|
|
ARID1B Q127_Q131del IDH1 R132L
|
cholangiocarcinoma
|
no benefit
|
Pamiparib
|
Preclinical - Pdx & cell culture |
Actionable |
In a preclinical study, a cholangiocarcinoma patient-derived xenograft (PDX) cell line harboring IDH1 R132L and ARID1B Q127_Q131del was insensitive to Pamiparib (BGB-290) in culture and did not inhibit tumor growth in the patient-derived xenograft (PDX) model (PMID: 36374558).
|
36374558
|
|
IDH1 R132G
|
chondrosarcoma
|
predicted - sensitive
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, Tibsovo (ivosidenib) treatment was tolerated, substantially decreased plasma 2-HG levels, and resulted in a median progression-free survival of 5.6 months and stable disease in 52% (11/21) of patients with chondrosarcoma harboring IDH1 mutations, including IDH1 R132G (n=3) (PMID: 32208957; NCT02073994).
|
32208957
|
|
IDH1 R132G
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
FDA approved - On 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...
32416072
detail...
|
|
IDH1 R132G
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On 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...
29860938
detail...
|
|
IDH1 R132G
|
acute myeloid leukemia
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839).
|
detail...
29860938
detail...
|
|
IDH1 R132G
|
myelodysplastic syndrome
|
sensitive
|
Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) was tolerated and resulted in a complete response (CR) in 44% (7/16), partial response (PR) in 6% (1/16), and marrow CR in 31% (5/16) of patients with relapsed or refractory myelodysplastic syndrome harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a hematologic improvement in >/=1 lineages achieved by 69% (11/16) of patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 7053; NCT02074839).
|
detail...
detail...
detail...
|
|
IDH1 R132G
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) 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 (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248).
|
35443108
detail...
detail...
|
|
IDH1 R132G
|
acute myeloid leukemia
|
sensitive
|
Olutasidenib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase II trial (Study 2102-HEM-101) that supported FDA approval, Rezlidhia (olutasidenib) treatment resulted in an objective response rate of 46% (57/123, 37 complete remission (CR), 4 CR with partial hematologic recovery, 14 CR with incomplete recovery, 1 morphologic leukemia-free state, 1 partial response) in patients with relapsed/refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132G/C/H/L/S) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574).
|
detail...
detail...
detail...
|
|
IDH1 R132G
|
acute myeloid leukemia
|
sensitive
|
BAY1436032
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132G in culture (PMID: 28232670).
|
28232670
|
|
IDH1 R132G
|
Advanced Solid Tumor
|
predicted - sensitive
|
DS-1001b
|
Preclinical - Biochemical |
Actionable |
In a preclinical study, transformed human cells expressing IDH1 R132G demonstrated sensitivity to DS-1001b in culture, resulting in reduced production of the oncometabolite 2-hydroxyglutarate (2-HG) (PMID: 31727689).
|
31727689
|
|
IDH1 R132G IDH1 D279N IDH1 G289D
|
acute myeloid leukemia
|
predicted - resistant
|
Ivosidenib
|
Case Reports/Case Series |
Actionable |
In a Phase I trial, IDH1 G289D and D279N were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132G who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839).
|
32380538
|
|
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
|
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
|
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
|
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
|
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
|
|
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
|
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 second or later-line therapy for patients with cholangiocarcinoma harboring IDH1 mutations (PMID: 36372281; ESMO.org).
|
detail...
36372281
|
|
IDH1 mutant
|
cholangiocarcinoma
|
sensitive
|
Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) is included in guidelines as subsequent therapy (category 1) for cholangiocarcinoma patients harboring IDH1 mutations (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
|
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
|
myelodysplastic syndrome
|
sensitive
|
Ivosidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) was tolerated and resulted in a complete response (CR) in 44% (7/16), partial response (PR) in 6% (1/16), and marrow CR in 31% (5/16) of patients with relapsed or refractory myelodysplastic syndrome harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a hematologic improvement in >/=1 lineages achieved by 69% (11/16) of patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 7053; NCT02074839).
|
detail...
detail...
detail...
|
|
IDH1 mutant
|
myelodysplastic syndrome
|
sensitive
|
Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) is included in guidelines for patients with myelodysplastic syndrome harboring an IDH1 mutation who progressed or failed to respond to prior treatment (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
|
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
|
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
|
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
|
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
|
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
|
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
|
anaplastic astrocytoma
|
not applicable
|
N/A
|
Guideline |
Diagnostic |
IDH1 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org).
|
detail...
|
|
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 |
Diagnostic |
IDH1 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (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
|
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
|
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
|
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
|
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
|
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
|
cholangiocarcinoma
|
no benefit
|
Durvalumab + Olaparib
|
Phase II |
Actionable |
In a Phase II trial, combination treatment with Lynparza (olaparib) and Imfinzi (durvalumab) was well tolerated but failed to demonstrate efficacy in patients with advanced cholangiocarcinoma harboring mutations in IDH1 or IDH2, with no objective responses, a disease control rate of 30% (3/10, 3 stable disease), and a median progression-free survival of 1.97 months (J Clin Oncol 41, 2023 (suppl 16; abstr 4099); NCT03991832).
|
detail...
|
|
IDH1 mutant
|
low grade glioma
|
predicted - sensitive
|
Vorasidenib
|
Phase I |
Actionable |
In a Phase I trial, Voranigo (vorasidenib) treatment resulted in an objective response in 13.6% (3/22, 1 partial response, 2 minor response) and stable disease in 72.7% (16/22) of patients with non-enhancing low-grade glioma harboring mutations in IDH1 (n=20) or IDH2 (n=1), with a median progression-free survival of 36.8 months, and resulted in stable disease as best response in 56.7% (17/30) of patients with enhancing tumors harboring mutations in IDH1 (n=28) or IDH2 (n=2) (PMID: 34078652; NCT02481154).
|
34078652
|
|
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
|
sensitive
|
Azacitidine + Ivosidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) 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 (azacitidine) 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
|
acute myeloid leukemia
|
sensitive
|
Azacitidine + Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) 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
|
Olutasidenib
|
FDA approved - Has Companion Diagnostic |
Actionable |
In a Phase II trial (Study 2102-HEM-101) that supported FDA approval, Rezlidhia (olutasidenib) treatment resulted in an objective response rate of 46% (57/123, 37 complete remission (CR), 4 CR with partial hematologic recovery, 14 CR with incomplete recovery, 1 morphologic leukemia-free state, 1 partial response) in patients with relapsed/refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574).
|
detail...
detail...
detail...
|
|
IDH1 mutant
|
acute myeloid leukemia
|
sensitive
|
Olutasidenib
|
Guideline |
Actionable |
Rezlidhia (olutasidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).
|
detail...
|
|
IDH1 mutant
|
myeloid neoplasm
|
predicted - sensitive
|
Ivosidenib + Venetoclax
|
Phase Ib/II |
Actionable |
In a Phase Ib/II trial, combination treatment with Tibsovo (ivosidenib) and Venclexta (venetoclax) demonstrated safety and efficacy in patients with advanced myeloid malignancies harboring IDH1 mutations, and led to a CRc (complete response (CR) + CR with partial hematologic recovery + CR with incomplete hematologic recovery) rate of 83% (10/12), median event-free survival (EFS) of 11 mo, 12-mo EFS rate of 50%, median overall survival (OS) of 42.1 mo, and 24-mo OS rate of 58% (PMID: 37102976; NCT03471260).
|
37102976
|
|
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
|
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
|
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
|
high grade glioma
|
sensitive
|
Olaparib + Radiotherapy
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, treatment with Lynparza (olaparib) enhanced the sensitivity of a glioma cell line harboring an IDH1 mutation to radiation therapy in culture, resulting in decreased survival compared to radiation therapy alone (PMID: 32494639).
|
32494639
|
|
IDH1 mutant
|
myeloid neoplasm
|
predicted - sensitive
|
Azacitidine + Ivosidenib + Venetoclax
|
Phase Ib/II |
Actionable |
In a Phase Ib/II trial, Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) and Venclexta (venetoclax) demonstrated safety and efficacy in patients with IDH1-mutant advanced myeloid malignancies, and led to a CRc (complete response (CR) + CR with partial hematologic recovery + CR with incomplete hematologic recovery) rate of 90% (17/19), 12-mo event-free survival (EFS) rate of 84%, 24-mo overall survival (OS) rate of 75%, and median EFS and OS were not reached (PMID: 37102976; NCT03471260).
|
37102976
|
|
IDH1 mutant
|
high grade glioma
|
sensitive
|
Radiotherapy + Veliparib
|
Preclinical - Cell line xenograft |
Actionable |
In a preclinical study, treatment with Veliparib (ABT-888) enhanced the sensitivity of a glioma cell line xenograft model harboring an IDH1 mutation to radiation therapy, resulting in increased survival compared to radiation therapy alone, with a median overall survival of 21 days vs 14 days, respectively (PMID: 32494639).
|
32494639
|
|
IDH1 act mut
|
malignant astrocytoma
|
sensitive
|
Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) is included in guidelines for patients with astrocytoma harboring an IDH1 activating mutation (NCCN.org).
|
detail...
|
|
IDH1 act mut
|
high grade glioma
|
predicted - sensitive
|
Ivosidenib
|
Clinical Study |
Actionable |
In a retrospective analysis, Tibsovo (ivosidenib) treatment was well tolerated in patients with glioma harboring an IDH1 mutation, and resulted in a partial response in 13.6% (3/22), minor response in 22.7% (5/22), and stable disease in 54.5% (12/22) of patients with nonenhancing disease, and stable disease in 62.5% (5/8) of patients with enhancing disease (PMID: 38496920).
|
38496920
|
|
IDH1 act mut
|
oligodendroglioma
|
sensitive
|
Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) is included in guidelines for patients with oligodendroglioma harboring an IDH1 activating mutation (NCCN.org).
|
detail...
|
|
IDH1 act mut
|
chondrosarcoma
|
sensitive
|
Ivosidenib
|
Guideline |
Actionable |
Tibsovo (ivosidenib) is included in guidelines as systemic therapy for patients with conventional or dedifferentiated chondrosarcoma harboring an IDH1 activating mutation (NCCN.org).
|
detail...
|
|
IDH1 act mut
|
low grade glioma
|
predicted - sensitive
|
Ivosidenib
|
Clinical Study |
Actionable |
In a retrospective analysis, Tibsovo (ivosidenib) treatment was well tolerated in patients with glioma harboring an IDH1 mutation, and resulted in a partial response in 13.6% (3/22), minor response in 22.7% (5/22), and stable disease in 54.5% (12/22) of patients with nonenhancing disease, and stable disease in 62.5% (5/8) of patients with enhancing disease (PMID: 38496920).
|
38496920
|
|
IDH1 act mut
|
oligodendroglioma
|
sensitive
|
Vorasidenib
|
Guideline |
Actionable |
Voranigo (vorasidenib) is included in guidelines as adjuvant therapy for patients with WHO grade 2 1p19q codeleted oligodendroglioma harboring an IDH1 activating mutation (NCCN.org).
|
detail...
|
|
IDH1 act mut
|
astrocytoma, IDH-mutant, grade 2
|
sensitive
|
Vorasidenib
|
Guideline |
Actionable |
Voranigo (vorasidenib) is included in guidelines as adjuvant therapy for patients with WHO grade 2 astrocytoma harboring an IDH1 activating mutation (NCCN.org).
|
detail...
|
|
IDH1 act mut
|
chondrosarcoma
|
predicted - sensitive
|
Olutasidenib
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, Rezlidhia (olutasidenib) treatment demonstrated acceptable safety and preliminary clinical activity in patients with IDH1-mutant intrahepatic cholangiocarcinoma, and led to stable disease in 31% (4/13) of evaluable patients (J Clin Oncol 38, no. 5_suppl (May 28, 2020); NCT03684811).
|
detail...
|
|
IDH1 act mut
|
intrahepatic cholangiocarcinoma
|
predicted - sensitive
|
Olutasidenib
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, Rezlidhia (olutasidenib) treatment demonstrated acceptable safety and preliminary clinical activity in patients with IDH1-mutant intrahepatic cholangiocarcinoma, and led to stable disease in 23% (6/23) of the evaluable patients (J Clin Oncol 38, no. 5_suppl (May 28, 2020); NCT03684811).
|
detail...
|
|
IDH1 act mut
|
cholangiocarcinoma
|
predicted - sensitive
|
LY3410738
|
Phase I |
Actionable |
In a Phase I trial, LY3410738 treatment demonstrated safety and resulted in D-2-HG inhibition in patients with IDH-mutant advanced solid tumors, and led to partial response in 1 and stable disease in 22 of 42 patients with relapsed or refractory cholangiocarcinoma and partial response in 3 and stable disease in 9 of 22 patients with glioma (Cancer Res (2023) 83 (8_Supplement): CT098; NCT04521686).
|
detail...
|
|
IDH1 act mut
|
brain glioma
|
predicted - sensitive
|
LY3410738
|
Phase I |
Actionable |
In a Phase I trial, LY3410738 treatment demonstrated safety and resulted in D-2-HG inhibition in patients with IDH-mutant advanced solid tumors, and led to partial response in 1 and stable disease in 22 of 42 patients with relapsed or refractory cholangiocarcinoma and partial response in 3 and stable disease in 9 of 22 patients with glioma (Cancer Res (2023) 83 (8_Supplement): CT098; NCT04521686).
|
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
|
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
|
oligodendroglioma
|
sensitive
|
Vorasidenib
|
FDA approved |
Actionable |
In a Phase III trial l (INDIGO) that supported FDA approval, Voranigo (vorasidenib) treatment significantly improved progression-free survival (27.7 vs 11.1 months, HR 0.39, p<0.001) and time to next intervention (HR 0.26, p<0.001) compared to placebo in adult and pediatric patients 12 years and older with WHO grade 2 oligodendroglioma or astrocytoma harboring susceptible IDH1 or IDH2 mutations, including IDH1 R132H/C/G/L/S (PMID: 37272516; NCT04164901).
|
37272516
detail...
|
|
IDH1 R132X
|
astrocytoma, IDH-mutant, grade 2
|
sensitive
|
Vorasidenib
|
FDA approved |
Actionable |
In a Phase III trial l (INDIGO) that supported FDA approval, Voranigo (vorasidenib) treatment significantly improved progression-free survival (27.7 vs 11.1 months, HR 0.39, p<0.001) and time to next intervention (HR 0.26, p<0.001) compared to placebo in adult and pediatric patients 12 years and older with WHO grade 2 astrocytoma or oligodendroglioma harboring susceptible IDH1 or IDH2 mutations, including IDH1 R132H/C/G/L/S (PMID: 37272516; NCT04164901).
|
detail...
37272516
|
|
IDH1 R132X
|
brain glioma
|
predicted - sensitive
|
Olutasidenib
|
Phase Ib/II |
Actionable |
In a Phase Ib/II trial, Rezlidhia (olutasidenib) treatment was well tolerated and did not meet the primary endpoint, with an objective response rate of 8% (2/25, both partial responses) but led to a disease control rate of 48% (12/25) in patients with glioma harboring IDH1 R132H (n=22), R132L (n=2), R132C (n=1), or R132G (n=1) (PMID: 35639513; NCT04380012).
|
35639513
|
|
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 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
|
predicted - sensitive
|
LY3410738
|
Phase I |
Actionable |
In a Phase I trial, LY3410738 demonstrated safety and inhibited D-2-HG in patients with relapsed or refractory IDH-mutant acute myeloid leukemia, resulting in a composite complete remission (CRc) rate of 38% (12/32, 5 CR, 2 CRh, 5 CRi/CRp) in IDH inhibitor-naive patients harbor IDH1 R132 mutations (Cancer Res (2023) 83 (8_Supplement): CT026; NCT04603001).
|
detail...
|
