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BIOMARKER:

IDH2 R172K

i
Other names: IDH2, Isocitrate Dehydrogenase (NADP(+)) 2, Isocitrate Dehydrogenase (NADP(+)) 2, Mitochondrial, Isocitrate Dehydrogenase 2 (NADP+), Mitochondrial, Isocitrate Dehydrogenase [NADP], Mitochondrial, Oxalosuccinate Decarboxylase, NADP(+)-Specific ICDH, ICD-M, IDH, IDP, MNADP-IDH, D2HGA2, IDHM, IDPM
Entrez ID:
Related biomarkers:
Related tests:
23d
The Idylla™ IDH1-2 Mutation Assay Kit: A tool for mutation detection in IDH1 and IDH2 genes (AACR 2024)
With advancements in molecular diagnostics and precision therapy, IDH inhibitors such as ivosidenib, vorasidenib and enasidenib are now mainstay in management of patients with a susceptible mutation. The Idylla™ IDH1-2 Mutation Assay Kit (RUO) is a fully automated qPCR assay for the qualitative detection of 15 common mutations in IDH1 (R132C/H/G/S/L) and IDH2 (R140Q/L/G/W, R172K/M/G/W/S) at codon level. The Idylla™ IDH1-2 Mutation Assay Kit demonstrates a high concordance with established reference methods across a range of different specimen types.
KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH1 mutation • IDH2 mutation • KIT mutation • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R140 • IDH2 R172
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Idylla™ IDH1-2 Mutation Assay
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Tibsovo (ivosidenib) • Idhifa (enasidenib) • vorasidenib (S95032)
1m
A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH (clinicaltrials.gov)
P1, N=75, Recruiting, Hutchmed | Trial completion date: Sep 2023 --> Jun 2025 | Trial primary completion date: Sep 2023 --> Sep 2024
Trial completion date • Trial primary completion date • Metastases
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R172
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HMPL-306
2ms
Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations (clinicaltrials.gov)
P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
Enrollment closed
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132L • IDH1 R132S • IDH1 R132V • IDH2 R172 • IDH2 R172G
|
Lynparza (olaparib)
4ms
NCI-2019-03057: Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation (clinicaltrials.gov)
P2, N=94, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH wild-type • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132L • IDH1 R132S • IDH1 R132V • IDH2 R172 • IDH2 R172G
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Lynparza (olaparib)
4ms
Trial completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132 • IDH2 R172
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vorasidenib (S95032)
5ms
A randomized double-blind Phase 3 study of vorasidenib vs placebo in patients with mutant IDH1/2 diffuse glioma (INDIGO): exploratory analysis of variant allele frequency and progression-free survival (SNO 2023)
In the first randomized Phase 3 study of a targeted therapy in grade 2 mIDH1/2 glioma, vorasidenib prolonged median PFS by BIRC, relative to placebo, irrespective of IDH1/2 VAF.
Clinical • P3 data
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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IDH1 mutation • CDKN2A deletion • IDH1 R132H • IDH2 R172K • IDH1 R132 • IDH2 R172
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vorasidenib (S95032)
5ms
Adjuvant post-surgery treatment of recurrent IDH2 mutant anaplastic oligodentroglioma (AO) with IDH2 inhibitor, Enasidenib: a case report (SNO 2023)
Introduction: Recent phase III trial presented by Mellinghoff at 2023 ASCO demonstrated successful treatment of Isocitrate dehydrogenase (IDH)–mutant grade 2 gliomas with Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes. Ivosidenib and enasidenib are separate inhibitors of mutant IDH1 and IDH2, which have shown single-agent activity for the treatment of IDH1- or IDH2-mutant acute myeloid leukemia but the effect in the treatment of glioma is uncertain...The patient underwent surgery resection, radiation and Temozolomide (TMZ), and 4 cycles of adjuvant TMZ...Clinically, the patient has no symptoms from tumor. Our case review found post-surgery therapy with IDH2 inhibitor Enasidenib for IDH2 mutant recurrent AO is tolerated and could postpone next intervention such as re-radiation or re-challenge with TMZ.
Clinical • Surgery • Post-surgery
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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IDH1 mutation • IDH2 mutation • IDH2 R172K • IDH2 R172
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temozolomide • Tibsovo (ivosidenib) • Idhifa (enasidenib) • vorasidenib (S95032)
5ms
Enrollment open
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
|
Lynparza (olaparib)
5ms
Development of a Closed System qPCR Assay to Detect Mutations in IDH1/IDH2 in Patients with Acute Myeloid Leukemia (AML) (ASH 2023)
Additionally, several IDH1/IDH2 inhibitors such as ivosidenib and enasidenib have been approved by the FDA for treatment of AML patients with IDH1 and IDH2 mutations respectively. We have prototyped 18-plex assay designed to detect 7 IDH1 and 10 IDH2 mutations and call out its corresponding codon in EDTA whole blood samples using a single cartridge at an estimated LoD of 1%.
Clinical
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH1 mutation • IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R140 • IDH2 R172
|
Tibsovo (ivosidenib) • Idhifa (enasidenib)
5ms
Final Results of the Phase Ib/II Study Evaluating Enasidenib in Combination with Venetoclax in Patients with IDH2-Mutated Relapsed/Refractory Myeloid Malignancies (ASH 2023)
Almost all pts had AML, except one with MDS who progressed on treatment with azacitidine. The combination of ENA and VEN is safe and well tolerated in pts with R/R mIDH2 myeloid malignancies. The ENA-VEN combination compares favorably to ENA single-agent in this patient population. Further studies of targeted combination therapies using IDH2 and BCL2 inhibitors are warranted.
Clinical • P1/2 data • Combination therapy • IO biomarker
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IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH2 mutation • IDH2 R172K • IDH2 R140Q • IDH2 R140 • IDH2 R172
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Venclexta (venetoclax) • azacitidine • Idhifa (enasidenib)
5ms
Evaluation of the Idylla Rapid IDH1/2 Mutation Assay in FFPE glioma samples (AMP 2023)
The Idylla Rapid IDH1/2 Mutation Assay had 92% concordance with NGS for FFPE sections. Compared with Idylla EGFR and KRAS assays (previously published) both control and target Cqs were considerably higher using the same number of sections or amount of DNA. A large DNA input requires stewardship for effective tissue utilization for molecular testing, especially in glioma biopsy samples, which may be limited.
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH1 mutation • IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH2 R140 • IDH2 R172
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Idylla™ EGFR Mutation Test • Idylla™ KRAS Mutation Test
6ms
Enrollment closed
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
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Lynparza (olaparib)
8ms
Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations (clinicaltrials.gov)
P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024
Trial completion date • Trial primary completion date • Metastases
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
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Lynparza (olaparib)
9ms
Clinical Significance of IDH Mutations and MGMT Promoter Methylation among WHO Classified CNS Tumors in Major Tertiary Care Unit of Pakistan (AMP Europe 2023)
Practical implementation of routine molecular work-up of CNS tumors is compromised by impractically long turnaround times and economic restraints. Based on our results, we advocate a stepwise approach, providing fast-track results obtained by MLPA for first-line therapy decisions within a week after surgery.
Clinical
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase)
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IDH1 mutation • IDH2 mutation • MGMT promoter methylation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R172
11ms
IDENTIFICATION OF CLINICALLY RELEVANT VARIANT-LEVEL SEX-BIAS IN SF3B1 K700/K666 AND IDH2 R140/R172 (EHA 2023)
This is the first comprehensive study to compare the sex ratio of driver genes at the variant level in a large cohort of hematological malignancies. Our findings extend the set of known sex-biased variant and support the hypothesis that male and female may have different mechanisms of oncogenesis, associated with potentiallydifferent outcomes, which needs to be further explored for precision medicine. Somatic mutation, Mutation analysis, MDS/AML
Clinical
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SF3B1 (Splicing Factor 3b Subunit 1)
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IDH2 R172K • SF3B1 K700E • IDH1 R132 • IDH2 R140 • IDH2 R172
11ms
A PHASE 1 STUDY OF HMPL-306, A DUAL INHIBITOR OF MUTANT ISOCITRATE DEHYDROGENASE (IDH) 1 AND 2, IN PTS WITH RELAPSED/REFRACTORY MYELOID HEMATOLOGICAL MALIGNANCIES HARBORING IDH1 AND/OR 2 MUTATIONS (EHA 2023)
Combing with safety, tolerability, PK/PD and preliminary efficacy, the RP2D was set as 250 mg QD at Cycle 1, and then with 150 mg QD from Cycle 2. Dose expansion is ongoing. Clinical trialinformation: NCT04272957.
Clinical • P1 data
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH1 mutation • IDH2 mutation • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R172
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HMPL-306
11ms
A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH (clinicaltrials.gov)
P1, N=75, Recruiting, Hutchmed | Trial completion date: Jan 2023 --> Sep 2023 | Trial primary completion date: Jan 2023 --> Sep 2023
Trial completion date • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R172
|
HMPL-306
1year
Preclinical characteristic of HMPL-306, a CNS-penetrable dual inhibitor of mutant IDH1 and IDH2 (AACR 2023)
Oral administration of HMPL-306 remarkably decreased 2-HG level in plasma and tumor tissues in xenograft models carrying mIDH1 or mIDH2 and the inhibition is more potent and durable than either ivosidenib or enasidenib at the same dose...Combination treatment of HMPL-306 and azacitidine synergized in releasing the differentiation block in mIDH AML cells. HMPL-306 is a potent, dual inhibitor of IDH1/2 mutation. The strong activity and favorable PK profiles support further clinical evaluation.
Preclinical
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH1 mutation • IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH2 R172
|
azacitidine • Tibsovo (ivosidenib) • Idhifa (enasidenib) • HMPL-306
1year
Natural and Synthetic 2-Oxogluturate Derivatives are Substrates for Oncogenic Variants of Human Isocitrate Dehydrogenase 1 and 2. (PubMed, J Biol Chem)
Furthermore, NMR and mass spectrometry studies confirmed IDH1/2 variant-catalyzed production of alcohols in the cases of the 3-methyl-, 3-butyl-, and 3-benzyl-substituted 2OG derivatives; a crystal structure of 3-butyl-2OG with an IDH1 variant (R132C/S280F IDH1) reveals active site binding. The combined results highlight the potential for (i) IDH1/2 variant-catalyzed reduction of 2-oxoacids other than 2OG in cells, (ii) modulation of IDH1/2 variant activity by 2-oxoacid natural products, including some present in common foods, (iii) inhibition of IDH1/2 variants via active site binding rather than the established allosteric mode of inhibition, and (iv) possible use of IDH1/2 variants as biocatalysts.
Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH2 R172
1year
Venetoclax and azacitidine induced cytogenetic response in an elderly patient with IDH2- and DNMT3A-mutated refractory acute myeloid leukemia (PubMed, Rinsho Ketsueki)
He received a reduced dose of idarubicin and cytarabine therapy. Even 9 months after starting VEN+AZA, the patient is still alive and healthy without AML recurrence. Thus, VEN+AZA therapy may be highly effective for treating IDH2- and DNMT3A-mutated AML in elderly patients.
Journal
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IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1)
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DNMT3A mutation • IDH2 R172K • DNMT3A R882H • DNMT3A R882 • IDH2 R172
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Venclexta (venetoclax) • cytarabine • azacitidine • idarubicin hydrochloride
over1year
NCI-2019-03057: Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation (clinicaltrials.gov)
P2, N=94, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
Trial completion date • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
|
Lynparza (olaparib)
over1year
Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2. (PubMed, Sci Rep)
Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability...The homology model further revealed that changes in conformation and IDH2 protein stability appeared to be associated with these point mutations. Taken together, our findings provide information important for understanding the molecular mechanisms of IDH2 mutations in tumors.
Journal
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IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CCND1 (Cyclin D1) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
|
IDH2 mutation • IDH2 R172K • CCND1 expression • IDH wild-type • IDH2 R140Q • IDH2 R140 • IDH2 R172 • IDH2 R172G • IL6 expression • IDH2 overexpression
|
bortezomib
over1year
Phase I Study of TQB3455, a Selective Inhibitor of IDH2 with Favorable Safety and More Potent Efficacy to IDH2-R172K Mutation, for Acute Myeloid Leukemia and Myelodysplastic Syndrome (ASH 2022)
Enasidenib (ENA), the first selective IDH2 inhibitor, was associated with impressive response rates in relapsed/refractory (R/R) AML and was approved by FDA in 2017. TQB3455 is well-tolerated for myeloid malignancy at the R2PD of 100 mg qd. It also yield high rates of clinical response in pts with mIDH2 AML. Patients with IDH2-R172K mutation fared much better than IDH2-R140Q/W with regard to response, this is in line with outcome of TQB3455 in vitro but different from previous reports of ENA.
Clinical • P1 data
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FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH2 mutation • RAS mutation • IDH2 R172K • IDH2 R140Q • IDH2 R172
|
Idhifa (enasidenib) • TQB3455
over1year
AML-432 Overall Survival (OS) by IDH2 Mutant Allele (R140 or R172) in Patients With Late-Stage, Mutant-IDH2 Relapsed/Refractory Acute Myeloid Leukemia (AML) Treated With Enasidenib or Conventional Care Regimens (CCR) in the Randomized, Open-Label, Phase 3 IDHENTIFY Trial. (PubMed, Clin Lymphoma Myeloma Leuk)
Mutational burden and co-mutational profiles differed between patients with mIDH2-R140 and mIDH2-R172 relapsed/refractory AML. In the R172 subgroup, median OS and 1-year survival rate with enasidenib were approximately double those with CCR.
Clinical • P3 data • Journal • Tumor Mutational Burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
IDH2 mutation • IDH2 R172K • SRSF2 mutation • IDH2 R140Q • IDH2 R140 • IDH2 R172
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cytarabine • azacitidine • Idhifa (enasidenib)
over1year
Overall Survival (OS) by IDH2 Mutant Allele (R140 or R172) in Patients With Late-Stage, Mutant- IDH2 Relapsed/Refractory Acute Myeloid Leukemia (AML) Treated With Enasidenib or Conventional Care Regimens (CCR) in the Randomized, Open-Label, Phase 3 IDHENTIFY Trial (SOHO 2022)
Patients were randomized 1:1 to enasidenib 100-mg/day or CCR (azacitidine, intermediate- or low-dose Ara-C, or supportive care). Mutational burden and co-mutational profi les differed between patients with mIDH2-R140 and mIDH2-R172 relapsed/refractory AML. In the R172 subgroup, median OS and 1-year survival rate with enasidenib were approximately double those with CCR.
Clinical • P3 data • Tumor Mutational Burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
IDH2 mutation • IDH2 R172K • SRSF2 mutation • IDH2 R140Q • IDH2 R140 • IDH2 R172
|
cytarabine • azacitidine • Idhifa (enasidenib)
over1year
Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation. (PubMed, J Hematol Oncol)
In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH1 mutation • IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R172
over1year
Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations (clinicaltrials.gov)
P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2022 --> Jul 2023 | Trial primary completion date: Jul 2022 --> Jul 2023
Trial completion date • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
|
Lynparza (olaparib)
almost2years
IDENTIFICATION OF RAMAN SPECTROSCOPIC SIGNATURE OF IDH MUTATIONS IN AML IN VITRO MODEL (EHA 2022)
Conclusion The results confirm the utility of Raman spectroscopy/microscopy to identify the changes between mutated and wild type forms of IDH1/2 suggesting the potential of optical methods for studying point-mutations in cancer cells and subsequently screening of leukaemia. Further studies to improve and optimise the method and collect more data for machine learning are warranted.
Preclinical
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH1 mutation • IDH1 R132H • IDH2 R172K • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH2 R172
almost2years
Overall survival by IDH2 mutant allele (R140 or R172) in patients with late-stage mutant-IDH2 relapsed or refractory acute myeloid leukemia treated with enasidenib or conventional care regimens in the phase 3 IDHENTIFY trial. (ASCO 2022)
Pts were preselected to a CCR (azacitidine, intermediate- or low-dose Ara-C, or supportive care), and were then randomized 1:1 to ENA 100 mg/d or CCR in 28d cycles. Mutational burden and co-mutational profiles differed between pts with mIDH2-R140 and mIDH2-R172 R/R AML. ENA improved survival outcomes for pts with IDH2-R172 mutations, with median OS and 1-year survival rate approximately double those in the CCR arm.
Clinical • P3 data • Tumor Mutational Burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SRSF2 (Serine and arginine rich splicing factor 2)
|
TP53 mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • IDH2 R172K • SRSF2 mutation • JAK2 mutation • IDH2 R140Q • IDH2 R140 • IDH2 R172
|
cytarabine • azacitidine • Idhifa (enasidenib)
almost2years
Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma. (ASCO 2022)
Olaparib was well tolerated in this pt population. The study did not meet the pre-specified response-based threshold for moving to step 2, but prolonged SD was observed in pts with grades 2 and 3 histologies, suggesting olaparib monotherapy could be of clinical benefit in select pts. Grade 4 tumors per the 2021 WHO classification defined by histology or CDKN2A mutation derived minimal to no benefit from this drug highlighting the usefulness of this new classification for future patient stratification and trial design and suggesting investigation of this treatment earlier in the disease course might be of interest.
Clinical • P2 data • BRCA Biomarker • PARP Biomarker
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
|
IDH1 mutation • IDH2 mutation • CDKN2A deletion • CDKN2A mutation • IDH1 R132H • IDH2 R172K • IDH1 R132 • IDH2 R172 • IDH2 R172G
|
Lynparza (olaparib)
2years
Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO) (clinicaltrials.gov)
P3, N=340, Active, not recruiting, Institut de Recherches Internationales Servier | Recruiting --> Active, not recruiting
Enrollment closed
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132 • IDH2 R172
|
vorasidenib (S95032)
2years
IMPACT OF IDH1 AND IDH2 MUTATIONAL SUBGROUPS IN ACUTE MYELOID LEUKEMIA PATIENTS AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (EBMT 2022)
 Here we report significant beneficial impact of alloHCT on survival of AML with different IDH mutational subclasses, both for patients in first complete remission and r/r AML in need for salvage treatment, respectively. Poor prognosis was effectively mitigated by alloHCT regarding the respective disease stage. Therefore, some IDH1/2 mutational subclasses could be potentially implemented in standard AML risk stratification and therapeutic decision making.
Clinical
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)
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IDH1 mutation • IDH2 mutation • NPM1 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R172
over2years
Detection of 2-Hydroxyglutarate by 3.0-Tesla Magnetic Resonance Spectroscopy in Gliomas with Rare IDH Mutations: Making Sense of "False-Positive" Cases. (PubMed, Diagnostics (Basel))
Thus, the specificity of MRS for detecting IDH1/2 mutations was higher (81.3%) than that originally reported (72.2%). The detection of 2HG by MRS can aid in the diagnosis of rare, non-IDH1-R132H IDH1 and IDH2 mutations in gliomas.
Clinical • Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132 • IDH2 R172