Therapy Detail
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| Therapy Name | Enasidenib |
| Synonyms | |
| Therapy Description |
Idhifa (enasidenib) inhibits IDH2 to prevent 2HG formation, which may promote differentiation and inhibit proliferation of cancer cells (PMID: 28280273). Idhifa (enasidenib) is FDA-approved for use in patients with relapsed or refractory acute myeloid leukemia harboring an IDH2 mutation (R140Q/L/G/W, R172K/M/G/S/W) (FDA.gov). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Enasidenib | Idhifa | AG-221 | IDH2 Inhibitor 5 | Idhifa (enasidenib) inhibits IDH2 to prevent 2HG formation, which may promote differentiation and inhibit proliferation of cancer cells (PMID: 28280273). Idhifa (enasidenib) is FDA-approved for use in patients with relapsed or refractory acute myeloid leukemia harboring an IDH2 mutation (R140Q/L/G/W, R172K/M/G/S/W) (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| IDH2 mutant | hematologic cancer | sensitive | Enasidenib | Phase I | Actionable | In a Phase I study, Enasidenib (AG-221) demonstrated safety and efficacy in patients with hematological cancer harboring IDH2 mutations and included 8 CR, 1 CRp, 3 CRi, and 8 PR (ASH Meeting, Dec 2014, abstract #115). | detail... |
| IDH2 R172X | myelodysplastic syndrome | predicted - sensitive | Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) treatment was well tolerated and resulted in an overall response rate of 43% (9/21, 5 complete remission (CR), 1 partial remission, 1 marrow CR, 2 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were refractory to or progressed on hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
| IDH2 R140Q IDH2 L449V | leukemia | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and L449V in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q | glioblastoma | predicted - sensitive | Enasidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a glioblastoma cell line expressing IDH2 R140Q in culture and in xenograft models (PMID: 28193778). | 28193778 |
| IDH2 R172K | colorectal cancer | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a colorectal carcinoma cell line expressing IDH2 R172K in culture (PMID: 28193778). | 28193778 |
| IDH2 R172S | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172S is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 R140Q | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140Q is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R140Q | acute myeloid leukemia | sensitive | Enasidenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Enasidenib (AG-221) treatment reduced 2-hydroxyglutarate (2HG) levels and induced differentiation of leukemic blasts from acute myeloid leukemia (AML) patients harboring IDH2 R140Q in culture, and decreased 2HG levels and blast percentage and improved survival relative to Cytosar-U (cytarabine) treatment in IDH2 R140Q-mutant primary AML xenograft models (PMID: 28193778). | 28193778 |
| IDH2 R172K | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172K is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R172K | acute myeloid leukemia | sensitive | Enasidenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels and induced differentiation of leukemic blasts from acute myeloid leukemia (AML) patients harboring IDH2 R172K in culture (PMID: 28193778). | 28193778 |
| IDH2 mutant | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (R140Q/L/G/W, R172K/M/G/S/W) (PMID: 28588020; NCT01915498). | 28588020 detail... detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Enasidenib | Guideline | Actionable | Idhifa (enasidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). | detail... |
| IDH2 R140Q IDH2 A347T | acute myeloid leukemia | predicted - resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 A347T was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R140X | myelodysplastic syndrome | predicted - sensitive | Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) treatment was well tolerated and resulted in an overall response rate of 43% (9/21, 5 complete remission (CR), 1 partial remission, 1 marrow CR, 2 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were refractory to or progressed on hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
| IDH2 R140Q IDH2 A347T | leukemia | resistant | Enasidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a leukemia cell line expressing IDH2 R140Q and A347T was resistant to Idhifa (enasidenib) in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 R353H | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and R353H in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 E343V | leukemia | resistant | Enasidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a leukemia cell line expressing IDH2 R140Q and E343V was resistant to Idhifa (enasidenib) in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 T352A | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and T352A in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 I319M | acute myeloid leukemia | resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical study, IDH2 I319M was identified as an acquired mutation in trans with the original IDH2 R140Q in a patient with acute myeloid leukemia (AML), who developed resistance to Idhifa (enasidenib) after initial response, and coexpression of IDH2 I319M in trans or in cis with IDH2 R140Q conferred resistance to Idhifa (enasidenib) in culture, supporting a mechanism of variants cooperating to confer resistance (PMID: 29950729). | 29950729 |
| IDH2 R140Q IDH2 I319M | acute myeloid leukemia | resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 I319M was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R140L | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140L is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R140Q IDH2 Q316E | acute myeloid leukemia | resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical study, IDH2 Q316E was identified as an acquired mutation in trans with the original IDH2 R140Q in a patient with acute myeloid leukemia (AML), who developed resistance to Idhifa (enasidenib) after initial response, and coexpression of IDH2 Q316E in trans or in cis with IDH2 R140Q conferred resistance to Idhifa (enasidenib) in culture and in animal models of AML, supporting a mechanism of variants cooperating to confer resistance (PMID: 29950729). | 29950729 |
| IDH2 R140Q IDH2 V351I | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and V351I in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 E343V | acute myeloid leukemia | predicted - resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 E343V was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 V351I | acute myeloid leukemia | predicted - resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 V351I was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R172K | glioblastoma | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a glioblastoma cell line expressing IDH2 R172K in culture (PMID: 28193778). | 28193778 |
| IDH2 R140Q IDH2 Q316E | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and Q316E in culture (PMID: 36222845). | 36222845 |
| IDH2 R140W | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140W is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 N136S IDH2 R140Q | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and N136S in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 E345G | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and E345G in culture (PMID: 36222845). | 36222845 |
| IDH2 R172G | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172G is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 R140Q IDH2 G450S | leukemia | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and G450S in culture (PMID: 36222845). | 36222845 |
| IDH2 R172M | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172M is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 R172W | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172W is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 R140G | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140G is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R140Q IDH2 I319M | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and I319M in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 H348Q | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and H348Q in culture (PMID: 36222845). | 36222845 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT03383575 | Phase II | Azacitidine + Enasidenib Enasidenib | Azacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome | Recruiting | USA | 0 |
| NCT03839771 | Phase III | Ivosidenib Enasidenib | A Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy, Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myedysplastic Syndrome EB2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy (HOVON150AML) | Active, not recruiting | SWE | NOR | NLD | LUX | LTU | IRL | FRA | FIN | EST | ESP | DEU | CHE | BEL | AUT | AUS | 0 |
| NCT02813135 | Phase Ib/II | Ribociclib + Temozolomide + Topotecan Adavosertib + Carboplatin Enasidenib Lirilumab + Nivolumab Irinotecan + Olaparib | European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors (ESMART) | Recruiting | NLD | ITA | GBR | FRA | ESP | DNK | DEU | 0 |
| NCT03825796 | Phase II | CPX-351 + Enasidenib Cytarabine + Enasidenib Enasidenib | CPX-351 Plus Enasidenib for Relapsed AML | Active, not recruiting | USA | 0 |
| NCT05282459 | Phase Ib/II | Enasidenib | Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation | Active, not recruiting | USA | 0 |
| NCT03881735 | Phase II | Enasidenib | Enasidenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia With an IDH2 Gene Mutation | Withdrawn | USA | 0 |
| NCT06176989 | Phase II | Enasidenib | Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors | Recruiting | USA | 0 |
| NCT02273739 | Phase Ib/II | Enasidenib | Study of Orally Administered AG-221 in Subjects With Advanced Solid Tumors, Including Glioma, and With Angioimmunoblastic T-cell Lymphoma, With an IDH2 Mutation | Completed | USA | FRA | 0 |
| NCT03744390 | Phase II | Enasidenib | IDH2 (AG 221) Inhibitor in Patients With IDH2 Mutated Myelodysplastic Syndrome | Active, not recruiting | FRA | 0 |
| NCT02577406 | Phase III | Azacitidine Cytarabine Enasidenib | An Efficacy and Safety Study of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation (IDHENTIFY) | Completed | USA | TUR | ITA | GBR | FRA | ESP | DNK | DEU | CZE | CAN | BRA | BEL | AUT | AUS | 4 |
| NCT04203316 | Phase II | Enasidenib | Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Patients With an IDH2 Mutation | Recruiting | USA | CAN | 0 |
| NCT03515512 | Phase I | Enasidenib | IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation | Completed | USA | 0 |
| NCT03728335 | Phase I | Enasidenib | Enasidenib as Maintenance Therapy in Treating Patients With Acute Myeloid Leukemia With IDH2 Mutation After Donor Stem Cell Transplant | Recruiting | USA | 0 |
| NCT04522895 | Phase II | Enasidenib | IDH2-Post-Allo-Trial for Patients With IDH2-mut Myeloid Neoplasms After Allo-SCT | Completed | DEU | 0 |
| NCT01915498 | Phase Ib/II | Enasidenib | Phase 1/2 Study of Enasidenib (AG-221) in Adults With Advanced Hematologic Malignancies With an Isocitrate Dehydrogenase Isoform 2 (IDH2) Mutation | Completed | USA | FRA | 0 |
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