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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 | 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 | 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 | 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 | 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 | 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 | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... | |
| IDH1 mutant | acute myeloid leukemia | sensitive | Ivosidenib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839). | detail... detail... 29860938 | |
| IDH1 mutant | 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 | 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 | 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 | 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 | 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 | 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 | 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 | malignant 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 | 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 | glioblastoma multiforme | 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 | 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 multiforme | 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 | glioblastoma multiforme | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of secondary grade IV glioblastomas (NCCN.org). | detail... | |
| IDH1 mutant | malignant 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 | 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 | malignant 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 | malignant 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 | malignant 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 | 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 | 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 | predicted - sensitive | Daunorubicin + Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination therapy of Talzenna (talazoparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH1 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). | 29339439 | |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | 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 | grade III astrocytoma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org). | detail... |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT03430791 | Phase II | Ipilimumab + Nivolumab Nivolumab | Trial of Combination TTF(Optune), Nivolumab Plus/Minus Ipilimumab for Bevacizumab-naïve, Recurrent Glioblastoma | Recruiting |
| 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 |
| NCT02428855 | Phase II | Dasatinib | Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma | Completed |
| NCT03557359 | Phase II | Nivolumab | Nivolumab for Recurrent or Progressive IDH Mutant Gliomas | Recruiting |
| NCT03878095 | Phase II | AZD6738 + Olaparib | Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors | Recruiting |
| NCT04278781 | Phase II | Ivosidenib | AG-120 in People With IDH1 Mutant Chondrosarcoma | Recruiting |
| NCT02981940 | Phase II | Abemaciclib | A Study of Abemaciclib in Recurrent Glioblastoma | Active, not recruiting |
| NCT03212274 | Phase II | Olaparib | Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations | Recruiting |
| NCT02071862 | Phase I | CB-839 + Everolimus CB-839 + Erlotinib CB-839 + Docetaxel CB-839 CB-839 + Paclitaxel Cabozantinib + CB-839 | Study of the Glutaminase Inhibitor CB-839 in Solid Tumors | Completed |
| NCT02576444 | Phase II | Adavosertib + Olaparib Olaparib Olaparib + Vistusertib Capivasertib + Olaparib AZD6738 + Olaparib | OLAParib COmbinations (OLAPCO) | 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 |
| NCT03922555 | Phase I | ASTX727 | ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas | Recruiting |
| NCT04015700 | Phase I | GNOS-PV01 + INO-9012 + Ipilimumab + Nivolumab GNOS-PV01 + INO-9012 + Nivolumab | Neoantigen-based Personalized DNA Vaccine Combined With Immune Checkpoint Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma | Not yet recruiting |
| NCT04118036 | Phase II | Abemaciclib + Pembrolizumab | Abemaciclib + Pembrolizumab In Glioblastoma | Suspended |
| NCT03718767 | Phase II | Nivolumab | Nivolumab in People With IDH-Mutant Gliomas With and Without Hypermutator Phenotype | Recruiting |
| NCT03749187 | Phase I | Pamiparib + Temozolomide | BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas (PNOC017) | Recruiting |
| NCT02989857 | Phase III | Ivosidenib | Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy) | Active, not recruiting |
| 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 Patients With Newly Diagnosed Acute Myeloid Leukemia With an IDH1 and/or IDH2 Mutation | Active, not recruiting |
| 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 |
| NCT03701295 | Phase Ib/II | Azacitidine + Pinometostat | Pinometostat and Azacitidine in Treating Patients With Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia With 11q23 Rearrangement | Recruiting |
| NCT03207347 | Phase II | Niraparib | A Trial of Niraparib in BAP1 and Other DNA Double-Strand Break Repair Deficient Neoplasms (UF-STO-ETI-001) | Recruiting |
| NCT02525692 | Phase II | ONC201 | Oral ONC201 in Adult Recurrent Glioblastoma | Recruiting |
| NCT03173248 | Phase III | Azacitidine + Ivosidenib 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 |
| NCT03127735 | Phase I | BAY1436032 | BAY1436032 in Patients With Mutant IDH1(mIDH1) Advanced Acute Myeloid Leukemia (AML) | Completed |
| NCT02858895 | Phase II | MDNA55 | Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma | Completed |
| 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 |
| NCT03991832 | Phase II | Durvalumab + Olaparib | Study of Olaparib and Durvalumab in IDH-Mutated Solid Tumors | Not yet recruiting |
| NCT03047993 | Phase Ib/II | Azacitidine + CB-839 | Glutaminase Inhibitor CB-839 and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndrome | 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 |
| 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 |
| NCT02968940 | Phase II | Avelumab | Avelumab With Hypofractionated Radiation Therapy in Adults With Isocitrate Dehydrogenase (IDH) Mutant Glioblastoma | Completed |