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| Profile Name | IDH1 mutant |
| Gene Variant Detail | |
| Relevant Treatment Approaches |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| 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 | 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 + Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination therapy of Lynparza (olaparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH1 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). | 29339439 | |
| IDH1 mutant | myeloid neoplasm | predicted - sensitive | Azacitidine + Ivosidenib + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) and Venclexta (venetoclax) demonstrated safety and preliminary efficacy in patients with advanced myeloid malignancies harboring IDH1 mutations, resulted in an overall response rate of 100% (8/8) (EMJ Hematol. 2020;8(1):50-53; NCT03471260). | detail... | |
| IDH1 mutant | acute myeloid leukemia | sensitive | 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 | 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 | 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 | high grade glioma | not applicable | N/A | Guideline | Prognostic | IDH1 mutations are associated with a favorable prognosis in patients with glioma, and are associated with a survival benefit for patients treated with radiation or alkylator therapy (NCCN.org). | detail... | |
| IDH1 mutant | high grade glioma | not applicable | N/A | Clinical Study | Prognostic | In multiple clinical studies, including two meta-analyses, IDH1 mutations were associated with improved overall survival and progression free survival in patients with gliomas (PMID: 23817809, PMID: 26220714, PMID: 23894344). | 23894344 23817809 26220714 | |
| IDH1 mutant | high grade glioma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of gliomas (PMID: 23041832, PMID: 19755387, PMID: 19915484; NCCN.org). | detail... 23041832 19755387 19915484 | |
| IDH1 mutant | 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 | oligodendroglioma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). | detail... | |
| IDH1 mutant | acute myeloid leukemia | not applicable | N/A | Clinical Study | Prognostic | In two meta-analyses, IDH1 mutations were associated with a worse overall survival in patients with acute myeloid leukemia (PMID: 22616558, PMID: 23226625). | 22616558 23226625 | |
| IDH1 mutant | acute myeloid leukemia | 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 | high grade glioma | sensitive | Ivosidenib | Phase I | Actionable | In a Phase I trial, AG-120 demonstrated safety and preliminary efficacy in IDH1-mutant glioma patients (Neuro Oncol (2016) 18 (suppl 6): vi12). | 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 | cholangiocarcinoma | sensitive | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in guidelines as subsequent therapy for cholangiocarcinoma patients harboring IDH1 mutations (NCCN.org). | detail... | |
| IDH1 mutant | cholangiocarcinoma | sensitive | Ivosidenib | Phase III | Actionable | In a Phase III (ClarIDHy) trial, 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/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). | 32416072 | |
| 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 | 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 | 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 | chondrosarcoma | resistant | Dasatinib | Preclinical | Actionable | In a preclinical study, chondrosarcoma cells harboring IDH1 mutations were resistant to Sprycel (dasatinib) in culture (PMID: 27231123). | 27231123 | |
| IDH1 mutant | myeloid neoplasm | predicted - sensitive | Ivosidenib + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Tibsovo (ivosidenib) and Venclexta (venetoclax) combination therapy demonstrated safety and preliminary efficacy in patients with advanced myeloid malignancies harboring IDH1 mutations, resulted in an overall response rate of 67% (4/6) and 100% (6/6) at 400 mg and 800 mg doses, respectively (EMJ Hematol. 2020;8(1):50-53; NCT03471260). | detail... | |
| IDH1 mutant | 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 | high grade glioma | predicted - sensitive | AG-881 | Phase I | Actionable | In a Phase I trial, Vorasidenib (AG-881) treatment resulted in an objective response in 13.6% (3/21, 1 partial response, 2 minor response) and stable disease in 77.3% (17/21) of patients with recurrent or progressive non-enhancing glioma harboring mutations in IDH1 (n=20) or IDH2 (n=1), with 60.5% of the patients remained progression-free and alive at 24 months (J Clin Oncol 38: 2020 (suppl; abstr 2504); NCT02481154). | detail... | |
| IDH1 mutant | acute myeloid leukemia | sensitive | 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 | 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 | malignant astrocytoma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org). | detail... | |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH1 mutation were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 | |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | 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 | 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 | 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 | 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 | 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 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT03220646 | Phase II | Abemaciclib | The Purpose of This Study is to Test Any Good and Bad Effects of a Study Drug Called Abemaciclib (LY2835219) in Patients With Recurrent Brain Tumors. | Recruiting | ||
| NCT03878095 | Phase II | AZD6738 + Olaparib | Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors | Recruiting | ||
| NCT04396860 | Phase II | Temozolomide Ipilimumab + Nivolumab | Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma | Recruiting | ||
| NCT03212274 | Phase II | Olaparib | Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations | Recruiting | ||
| NCT04555577 | Phase I | MSC2490484A Temozolomide | Nedisertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma | Recruiting | ||
| NCT02858895 | Phase II | MDNA55 | Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma | Completed | ||
| NCT03922555 | Phase I | Decitabine and Cedazuridine | ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas | Recruiting | ||
| NCT02981940 | Phase II | Abemaciclib | A Study of Abemaciclib in Recurrent Glioblastoma | Active, not recruiting | ||
| NCT02576444 | Phase II | Adavosertib + Olaparib Olaparib Capivasertib + Olaparib AZD6738 + Olaparib | OLAParib COmbinations (OLAPCO) | Active, not recruiting | ||
| NCT03430791 | Phase II | Ipilimumab + Nivolumab Nivolumab | Trial of Combination TTF(Optune), Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma | Terminated | ||
| NCT03173248 | Phase III | Azacitidine Azacitidine + Ivosidenib | Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Patients With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation (AGILE) | Recruiting | ||
| NCT02481154 | Phase I | AG-881 | Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation | Active, not recruiting | ||
| NCT02071862 | Phase I | Everolimus + Telaglenastat Erlotinib + Telaglenastat Docetaxel + Telaglenastat Telaglenastat Paclitaxel + Telaglenastat Cabozantinib + Telaglenastat | Study of the Glutaminase Inhibitor CB-839 in Solid Tumors | Completed | ||
| NCT04015700 | Phase I | GNOS-PV01 + INO-9012 | Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma | Recruiting | ||
| NCT03749187 | Phase I | Pamiparib + Temozolomide | BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas (PNOC017) | Recruiting | ||
| NCT02428855 | Phase II | Dasatinib | Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma | Completed | ||
| NCT04576117 | Phase III | Selumetinib Selumetinib + Vinblastine | A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma | Recruiting | ||
| NCT02968940 | Phase II | Avelumab | Avelumab With Hypofractionated Radiation Therapy in Adults With Isocitrate Dehydrogenase (IDH) Mutant Glioblastoma | Completed | ||
| NCT02073994 | Phase I | Ivosidenib | Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation | Active, not recruiting | ||
| NCT04764474 | Phase I | HMPL-306 | A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH | Not yet recruiting | ||
| NCT02525692 | Phase II | ONC201 | Oral ONC201 in Recurrent GBM, H3 K27M Glioma, and Midline Glioma | Recruiting | ||
| NCT02677922 | Phase Ib/II | Azacitidine + Ivosidenib Azacitidine Azacitidine + Enasidenib | A Safety and Efficacy Study of Oral AG-120 Plus Subcutaneous Azacitidine and Oral AG-221 Plus Subcutaneous Azacitidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) | Active, not recruiting | ||
| NCT02989857 | Phase III | Ivosidenib | Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy) | Active, not recruiting | ||
| NCT04606316 | Phase I | Nivolumab Ipilimumab + Nivolumab | Surgical Nivolumab And Ipilimumab For Recurrent GBM | Recruiting | ||
| NCT02492737 | Phase I | AG-881 | Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation | Completed | ||
| NCT02632708 | Phase I | Enasidenib + Etoposide + Mitoxantrone Cytarabine + Enasidenib Cytarabine + Idarubicin + Ivosidenib Cytarabine + Daunorubicin + Enasidenib Cytarabine + Enasidenib + Idarubicin Etoposide + Ivosidenib + Mitoxantrone Cytarabine + Ivosidenib Cytarabine + Daunorubicin + Ivosidenib | Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation | Active, not recruiting | ||
| NCT04195555 | Phase II | Ivosidenib | Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial) | Recruiting | ||
| NCT03701295 | Phase Ib/II | Azacitidine + Pinometostat | Pinometostat and Azacitidine in Treating Patients With Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia With 11q23 Rearrangement | Completed | ||
| NCT03991832 | Phase II | Durvalumab + Olaparib | Study of Olaparib and Durvalumab in IDH-Mutated Solid Tumors | Recruiting | ||
| NCT04629209 | Phase II | ONC201 | A Phase II, Open Label Study of ONC201 in Adults With EGFR-low Glioblastoma | Not yet recruiting | ||
| NCT03139916 | Phase II | Bavituximab + Temozolomide | Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma | Active, not recruiting | ||
| NCT04762602 | Phase I | HMPL-306 | A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations | Not yet recruiting | ||
| NCT03557359 | Phase II | Nivolumab | Nivolumab for Recurrent or Progressive IDH Mutant Gliomas | Recruiting | ||
| NCT04118036 | Phase II | Abemaciclib + Pembrolizumab | Abemaciclib + Pembrolizumab In Glioblastoma | Suspended | ||
| NCT03207347 | Phase II | Niraparib | A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) | Recruiting | ||
| NCT03127735 | Phase I | BAY1436032 | BAY1436032 in Patients With Mutant IDH1(mIDH1) Advanced Acute Myeloid Leukemia (AML) | Completed | ||
| NCT03047993 | Phase Ib/II | Azacitidine + Telaglenastat | Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome | Recruiting | ||
| NCT04278781 | Phase II | Ivosidenib | AG-120 in People With IDH1 Mutant Chondrosarcoma | Recruiting | ||
| NCT04774393 | Phase Ib/II | Decitabine and Cedazuridine + Ivosidenib + Venetoclax Decitabine and Cedazuridine + Enasidenib + Venetoclax | Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia | Not yet recruiting | ||
| NCT03718767 | Phase II | Nivolumab | Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype | Recruiting |