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| Profile Name | IDH1 R132I |
| Gene Variant Detail | |
| Relevant Treatment Approaches | IDH Inhibitor (Pan) IDH1 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| IDH1 R132S | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | IDH1 Inhibitor | 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 | 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 | 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 | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Azacitidine + Ivosidenib | FDA approved - On 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). | 35443108 detail... detail... |
| 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 | cholangiocarcinoma | predicted - sensitive | IDH1 Inhibitor | 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 | Advanced Solid Tumor | predicted - sensitive | IDH1 Inhibitor | DS-1001b | Preclinical - Cell culture | 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 R132X | acute myeloid leukemia | no benefit | IDH1 Inhibitor | 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 | sensitive | IDH1 Inhibitor | 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 | 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 | low grade glioma | predicted - sensitive | IDH1 Inhibitor | 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 R132L | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Azacitidine + Ivosidenib | FDA approved - On 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). | 35443108 detail... detail... |
| IDH1 R132L | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | chondrosarcoma | predicted - sensitive | IDH1 Inhibitor | 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 | Advanced Solid Tumor | predicted - sensitive | IDH1 Inhibitor | DS-1001b | Preclinical - Cell culture | 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 R132L | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | cholangiocarcinoma | predicted - sensitive | IDH1 Inhibitor | 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 | Advanced Solid Tumor | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). | 28148839 | |
| 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 | glioblastoma | predicted - sensitive | IDH1 Inhibitor | 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 | 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 | 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 | 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 | decreased response | IDH1 Inhibitor | AGI-5198 + Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, AGI-5198 reverted the sensitivity of transformed cells over expressing IDH1 R132H to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
| 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 | 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 | 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 | Advanced Solid Tumor | predicted - sensitive | IDH1 Inhibitor | DS-1001b | Preclinical - Cell culture | 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 | 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 | 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 | colon carcinoma | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, colon carcinoma cells over expressing IDH1 R132H demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). | 28148839 | |
| IDH1 R132H | high grade glioma | sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Azacitidine + Ivosidenib | FDA approved - On 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). | 35443108 detail... detail... |
| IDH1 R132H | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | 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 | 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 | 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 | Advanced Solid Tumor | sensitive | BAY1895344 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with BAY1895344 resulted in decreased survival in cell lines expressing IDH1 R132H in culture (PMID: 34027408). | 34027408 | |
| 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 | cholangiocarcinoma | sensitive | IDH1 Inhibitor | 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 | Advanced Solid Tumor | sensitive | BAY1895344 + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and 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 | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | Advanced Solid Tumor | sensitive | Cisplatin + Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talazoparib (BMN-673) and Cisplatin synergistically inhibited growth of transformed cells over expressing IDH1 R132H in culture (PMID: 28148839). | 28148839 | |
| 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 | glioblastoma | sensitive | IDH1 Inhibitor | 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 | 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 | glioblastoma | predicted - sensitive | IDH1 Inhibitor | 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 | colorectal cancer | resistant | IDH1 Inhibitor | 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 | 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 | colorectal cancer | resistant | IDH1 Inhibitor | 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 | 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 | 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 Talazoparib (BMN-673)-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 | 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 | 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 | IDH Inhibitor (Pan) | AG-881 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AG-881 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 | low grade glioma | predicted - sensitive | IDH1 Inhibitor | 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 | 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 | |
| FLT3 D835Y IDH1 R132H | hematologic cancer | resistant | IDH1 Inhibitor | AGI-5198 | Preclinical - Cell culture | Actionable | In a preclinical study, AGI-5198, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). | 30651561 |
| FLT3 D835Y IDH1 R132H | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib, decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). | 30651561 | |
| FLT3 D835Y IDH1 R132H | hematologic cancer | sensitive | IDH1 Inhibitor | AGI-5198 + Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib, in combination with AGI-5198, synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). | 30651561 |
| ATRX loss IDH1 R132H | high grade glioma | predicted - sensitive | Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, Lynparza (olaparib) treatment inhibited viability of immortalized astrocytes expressing IDH1 R132H with loss of ATRX in culture (PMID: 34118569). | 34118569 | |
| ATRX loss IDH1 R132H | high grade glioma | predicted - sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) treatment inhibited viability of immortalized astrocytes expressing IDH1 R132H with loss of ATRX in culture (PMID: 34118569). | 34118569 | |
| IDH1 act mut | chondrosarcoma | sensitive | IDH1 Inhibitor | 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 | chondrosarcoma | predicted - sensitive | IDH1 Inhibitor | Olutasidenib | Phase Ib/II | Actionable | In a Phase I/II trial, Olutasidenib (FT-2102) 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 13 evaluable patients (J Clin Oncol 38, no. 5_suppl (May 28, 2020); NCT03684811). | detail... |
| IDH1 act mut | intrahepatic cholangiocarcinoma | predicted - sensitive | IDH1 Inhibitor | Olutasidenib | Phase Ib/II | Actionable | In a Phase I/II trial, Olutasidenib (FT-2102) 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 23 evaluable patients (J Clin Oncol 38, no. 5_suppl (May 28, 2020); NCT03684811). | detail... |
| IDH1 R132C IDH1 S280F | acute myeloid leukemia | predicted - resistant | IDH1 Inhibitor | 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 | IDH1 Inhibitor | 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 R132G | chondrosarcoma | predicted - sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Azacitidine + Ivosidenib | FDA approved - On 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). | 35443108 detail... detail... |
| IDH1 R132G | Advanced Solid Tumor | predicted - sensitive | IDH1 Inhibitor | DS-1001b | Preclinical - Cell culture | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | cholangiocarcinoma | predicted - sensitive | IDH1 Inhibitor | 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 | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 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 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 | |
| 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 | |
| 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 | IDH1 Inhibitor | AGI-5198 + Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib, in combination with AGI-5198, synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). | 30651561 |
| FLT3 D835Y IDH1 wild-type | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib, decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). | 30651561 | |
| FLT3 D835Y IDH1 wild-type | hematologic cancer | resistant | IDH1 Inhibitor | AGI-5198 | Preclinical - Cell culture | Actionable | In a preclinical study, AGI-5198, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). | 30651561 |
| 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 | chondrosarcoma | predicted - sensitive | IDH1 Inhibitor | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | IDH1 Inhibitor | 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 | high grade glioma | sensitive | IDH1 Inhibitor | 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 | sarcoma | decreased response | IDH1 Inhibitor | 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 | 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 | cholangiocarcinoma | predicted - sensitive | IDH1 Inhibitor | 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 | Advanced Solid Tumor | predicted - sensitive | IDH1 Inhibitor | DS-1001b | Preclinical - Cell culture | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | sarcoma | decreased response | IDH1 Inhibitor | AGI-5198 + Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
| IDH1 R132C | fibrosarcoma | predicted - sensitive | IDH Inhibitor (Pan) | AG-881 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AG-881 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 | 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 Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). | 28148839 | |
| 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 | 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 | 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 | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Azacitidine + Ivosidenib | FDA approved - On 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). | 35443108 detail... detail... |
| IDH1 R132C | acute myeloid leukemia | sensitive | IDH1 Inhibitor | 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 | 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 mutant | myeloid neoplasm | predicted - sensitive | IDH1 Inhibitor | 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 | 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 | myeloid neoplasm | predicted - sensitive | IDH1 Inhibitor | 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 + 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 | 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 | oligodendroglioma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). | detail... | |
| 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 | sensitive | IDH1 Inhibitor | 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 | 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 | 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 | sensitive | IDH1 Inhibitor | 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 | IDH1 Inhibitor | 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 | 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 | 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 | predicted - sensitive | IDH Inhibitor (Pan) | 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 | cholangiocarcinoma | sensitive | IDH1 Inhibitor | 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 | IDH1 Inhibitor | 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 | IDH1 Inhibitor | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in guidelines as subsequent therapy for cholangiocarcinoma patients harboring IDH1 mutations (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 | 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 | 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 | 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 | 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 | 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 | 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 | acute myeloid leukemia | predicted - sensitive | IDH1 Inhibitor | 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 | 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 | 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 | 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 | 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 | 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... | |
| ATRX loss IDH1 mut | malignant astrocytoma | not applicable | N/A | Guideline | Diagnostic | ATRX deficiency in combination with IDH mutation aids in the diagnosis of astrocytoma (NCCN.org). | detail... | |
| ATRX loss IDH1 mut | high grade glioma | predicted - sensitive | Gemcitabine + Radiotherapy | Phase I | Actionable | In a Phase I trial, Gemzar (gemcitabine) plus radiation therapy resulted in median overall survival of 73.5 months in 7 high-grade glioma patients with IDH mutated, non-codeleted tumors with ATRX loss (PMID: 26853339). | 26853339 |
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