P2, N=68, Active, not recruiting, Groupe Francophone des Myelodysplasies | Recruiting --> Active, not recruiting | Trial completion date: Feb 2023 --> Mar 2026

12 days ago

Enrollment closed • Trial completion date

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Idhifa (enasidenib)

29d

Somatic gene mutation patterns and burden influence outcomes with enasidenib in relapsed/refractory IDH2-mutated AML. (PubMed, Leuk Res)

In multivariable analyses, RAS and RTK pathway mutations were significantly associated with decreased overall survival, after adjusting for treatment arm, IDH2 variant, and mutational burden. Importantly, enasidenib-mediated survival benefit was more pronounced in patients with IDH2-R172 variants.

29 days ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1)

NRAS mutation • IDH2 mutation • DNMT3A mutation • TMB-L • IDH2 R140 • IDH2 R172

Idhifa (enasidenib)

29d

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. (PubMed, J Clin Pharmacol)

This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 probe drug), midazolam (CYP3A4 probe drug), omeprazole (CYP2C19 probe drug), and pioglitazone (CYP2C8 probe drug), in patients with AML or myelodysplastic syndrome. The parameters for omeprazole increased by 1.86 (90% CI: 1.33, 2.60) and 1.47 (0.93, 2.31)-fold, respectively, compared to omeprazole alone, while those for pioglitazone decreased to 0.80 (90% CI: 0.62, 1.03) and 0.87 (90% CI: 0.65, 1.16)-fold, respectively, in comparison to pioglitazone alone. These findings provide valuable insights into dose recommendations concerning drugs acting as substrates of CYP2D6, CYP2C9, CYP3A4, CYP2C19, and CYP2C8 when administered concurrently with enasidenib.

29 days ago

Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CYP2C9 (Cytochrome P450 Family 2 Subfamily C Member 9) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)

IDH2 mutation

Idhifa (enasidenib)

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma. (PubMed, EBioMedicine)

Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.

1 month ago

Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Idhifa (enasidenib)

2ms

Integrating Full Bayesian Inference and Student's t-Distribution Method for Enhanced Outlier Handling in Caffeine Population Pharmacokinetics: Assessing Drug-Drug Interactions with Enasidenib in Relapsed or Refractory AML and MDS Patients. (PubMed, J Clin Pharmacol)

This finding led to a specific recommendation in the package insert to avoid the concurrent use of certain CYP1A2 substrates with enasidenib, unless directed otherwise in the prescribing information. Furthermore, this research underlines the technical benefits of integrating full Bayesian inference and incorporating Student's t-distribution for residual error modeling in the PK field.

2 months ago

PK/PD data • Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2)

IDH2 mutation

Idhifa (enasidenib)

2ms

NCI-2022-02837: Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation (clinicaltrials.gov)

P1/2, N=48, Recruiting, Stanford University | Trial completion date: Jan 2024 --> Aug 2024 | Trial primary completion date: Jan 2024 --> Aug 2024

2 months ago

Trial completion date • Trial primary completion date

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Idhifa (enasidenib)

2ms

The Idyllaâ„¢ 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 Idyllaâ„¢ 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 Idyllaâ„¢ IDH1-2 Mutation Assay Kit demonstrates a high concordance with established reference methods across a range of different specimen types.

2 months ago

KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH1 mutation • IDH2 mutation • KIT mutation • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R140 • IDH2 R172

Idylla™ IDH1-2 Mutation Assay

Tibsovo (ivosidenib) • Idhifa (enasidenib) • vorasidenib (S95032)

2ms

NCI-2021-00893: Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)

P1/2, N=84, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1b/2 --> P1/2

2 months ago

Phase classification • Combination therapy

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Venclexta (venetoclax) • Tibsovo (ivosidenib) • Idhifa (enasidenib) • Inqovi (decitabine/cedazuridine)

2ms

Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)

P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual

2 months ago

Trial termination

Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • Sutent (sunitinib) • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical

2ms

A Study of Perpetrator Drug Interactions of Enasidenib in AML Patients (clinicaltrials.gov)

P1, N=40, Completed, Celgene | Active, not recruiting --> Completed

2 months ago

Trial completion

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)

IDH2 mutation • UGT1A1*1*1 • UGT1A1 mutation

Idhifa (enasidenib) • midazolam hydrochloride • omeprazole

2ms

Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors (clinicaltrials.gov)

P2, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

2 months ago

Enrollment open

Idhifa (enasidenib)

3ms

Enasidenib as Maintenance Therapy in Treating Patients With Acute Myeloid Leukemia With IDH2 Mutation After Donor Stem Cell Transplant (clinicaltrials.gov)

P1, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

3 months ago

Trial completion date • Trial primary completion date

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Idhifa (enasidenib)

3ms

P3; Trial completion date: Dec 2023 --> Mar 2024

3 months ago

Trial completion date

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)

IDH2 mutation • UGT1A1*1*1 • UGT1A1 mutation

Abbott RealTime IDH2

cytarabine • azacitidine • Idhifa (enasidenib) • hydroxyurea

3ms

Enasidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH2A Decentralized Trial (clinicaltrials.gov)

P2, N=15, Not yet recruiting, Washington University School of Medicine

3 months ago

New P2 trial

Idhifa (enasidenib)

3ms

AG-221-C-001: Phase 1/2 Study of Enasidenib (AG-221) in Adults With Advanced Hematologic Malignancies With an Isocitrate Dehydrogenase Isoform 2 (IDH2) Mutation (clinicaltrials.gov)

P1/2, N=345, Completed, Celgene | Active, not recruiting --> Completed

3 months ago

Trial completion

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)

IDH2 mutation • UGT1A1*1*1 • Chr t(15;17) • UGT1A1 mutation

Idhifa (enasidenib)

3ms

AG-221-AML-005: A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy (clinicaltrials.gov)

P1/2, N=130, Active, not recruiting, Celgene | Phase classification: P1b/2 --> P1/2

3 months ago

Phase classification

Tibsovo (ivosidenib) • Idhifa (enasidenib)

3ms

ENAVEN-AML: Study of Enasidenib and Venetoclax in IDH2-Mutated Blood Cancers (clinicaltrials.gov)

P1/2, N=27, Terminated, University Health Network, Toronto | Trial completion date: Jul 2023 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2023 --> Oct 2023; Insufficient Funding

3 months ago

Trial completion date • Trial termination • Trial primary completion date • Combination therapy • IO biomarker

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 R140 • IDH2 R172

Venclexta (venetoclax) • Idhifa (enasidenib)

4ms

Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors (clinicaltrials.gov)

P2, N=30, Not yet recruiting, National Cancer Institute (NCI)

4 months ago

New P2 trial

Idhifa (enasidenib)

4ms

MPN-RC 119: Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation (clinicaltrials.gov)

P2, N=6, Completed, John Mascarenhas | Trial completion date: Dec 2022 --> May 2023 | Trial primary completion date: Dec 2022 --> May 2023

4 months ago

Trial completion date • Trial primary completion date

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Jakafi (ruxolitinib) • Idhifa (enasidenib)

5ms

Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=15, Recruiting, City of Hope Medical Center | Phase classification: P1b --> P1 | Trial completion date: Mar 2024 --> May 2025 | Trial primary completion date: Mar 2024 --> May 2025

5 months ago

Phase classification • Trial completion date • Trial primary completion date • Combination therapy

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

KRAS mutation • NRAS mutation • IDH2 mutation • NF1 mutation • RAS mutation • CBL mutation • IDH2 R140 • IDH2 R172

Cotellic (cobimetinib) • Idhifa (enasidenib)

5ms

Durable responses in acute lymphoblastic leukaemia with the use of FLT3 and IDH inhibitors. (PubMed, Br J Haematol)

Patient 1 maintains a complete remission (CR) with enasidenib after intolerance to chemotherapy. Patient 3 was treated with venetoclax and gilteritinib at the time of relapse and maintained a CR with gilteritinib for 8 months. These cases suggest that FLT3 and IDH inhibitors could represent a viable therapeutic option for ALL patients with these mutations.

5 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

Venclexta (venetoclax) • Xospata (gilteritinib) • Idhifa (enasidenib)

5ms

Multicenter Pilot Clinical Trial of Enasidenib As Maintenance Therapy after Allogeneic Hematopoietic Cell Transplantation (alloHCT) in Patients with Acute Myeloid Leukemia (AML) Carrying IDH2 Mutations (TCT-ASTCT-CIBMTR 2024)

In conclusion, post-HCT maintenance therapy with enasidenib is safe and feasible with highly favorable survival outcomes in mIDH2 AML. Treatment delays and dose reductions were commonly seen; however, most patients completed their 2-years maintenance.

5 months ago

Clinical

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation • IDH1 R132 • IDH2 R140 • IDH2 R172

Idhifa (enasidenib)

5ms

Practice Patterns of Transplant Centers Regarding Maintenance Treatment Post Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia: A Survey on Behalf of the EBMT Acute Leukemia Working Party (ASH 2023)

9%) use hypomethylating agents (HMA) (azacitidine N=51 (82. 3%), decitabine N=6 (9. 6%), HMA with venetoclax N=23 (37%), HMA with donor lymphocyte infusion (DLI) N=38 (61%), or a combination of modalities in 42 (67...The most common choice was sorafenib in 82/93 (88. 2%) centers, midostaurin in 28 (30%), and gilteritinib in 30 (32...2%) use enasidenib... In this survey, the majority of responding EBMT-affiliated transplant centers is implementing post-transplant AML maintenance treatment, predominantly HMA and FLT3 inhibitors. Further studies are needed to clarify the appropriate strategy and duration of maintenance therapy. The study will help the EBMT to incorporate post-transplant strategies as a routine registry capture parameter.

5 months ago

Clinical

FLT3 (Fms-related tyrosine kinase 3)

FLT3 mutation

Venclexta (venetoclax) • sorafenib • Xospata (gilteritinib) • azacitidine • Rydapt (midostaurin) • decitabine • Idhifa (enasidenib)

5ms

A Phase 1b Multi-Center Study of the FLT3 Inhibitor Gilteritinib in Combination with the IDH1 Inhibitor Ivosidenib or the IDH2 Inhibitor Enasidenib for Patients with Relapsed or Refractory Acute Myeloid Leukemia Who Have Co-Occurring FLT3/IDH1 or FLT3/IDH2 Mutations (ASH 2023)

This study is partially supported by Astellas Pharma Global Development, Inc. The study population will include patients with AML with dual FLT3 and IDH1/IDH2 mutations R/R to initial intensive induction therapy, or for patients treated with low intensity therapy, the patient must be refractory to treatment with a single agent hypomethylating agent (HMA) or low dose cytarabine (LDAC) (at least two cycles) or an HMA/LDAC in combination with venetoclax (at least one cycle) or another standard of care therapy (e. g. gemtuzumab ozogamicin, glasdegib/LDAC). Patients with a history of autologous or allogeneic stem cell transplant for AML are permitted to participate in the study.

5 months ago

Clinical • P1 data • Combination therapy

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH1 mutation • IDH2 mutation • FLT3 mutation

Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • Tibsovo (ivosidenib) • Mylotarg (gemtuzumab ozogamicin) • Idhifa (enasidenib) • Daurismo (glasdegib)

6ms

MPN-RC 119: Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation (clinicaltrials.gov)

P2, N=6, Completed, John Mascarenhas | Recruiting --> Completed | N=32 --> 6 | Trial completion date: Apr 2025 --> Dec 2022 | Trial primary completion date: Apr 2024 --> Dec 2022

6 months ago

Trial completion • Enrollment change • Trial completion date • Trial primary completion date

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Jakafi (ruxolitinib) • Idhifa (enasidenib)

6ms

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.

6 months ago

Clinical • Surgery • Post-surgery

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

IDH1 mutation • IDH2 mutation • IDH2 R172K • IDH2 R172

temozolomide • Tibsovo (ivosidenib) • Idhifa (enasidenib) • vorasidenib (S95032)

6ms

Novel Approaches to Treatment of Acute Myeloid Leukemia Relapse Post Allogeneic Stem Cell Transplantation. (PubMed, Int J Mol Sci)

Those patients harboring targetable mutations might benefit from IDH1/2 inhibitors Ivosidenib and Enasidenib as well as FLT3 inhibitors Sorafenib and Gilteritinib in combination with HMA and DLI. Conversely, patients lacking targetable mutations actually benefit from the addition of Venetoclax...Overall, across studies, higher response rates and longer survival were observed in cases of pre-emptive intervention for molecular relapse. Future perspectives currently rely on the development of adoptive immunotherapeutic strategies mainly represented by CAR-T cells.

6 months ago

Review • Journal • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

Venclexta (venetoclax) • sorafenib • Xospata (gilteritinib) • Tibsovo (ivosidenib) • Idhifa (enasidenib)

6ms

Phase Ib/2 Study of Oral Decitabine/Cedazuridine (ASTX727) and Venetoclax in Combination with the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib: 2023 Update (ASH 2023)

AEs were anticipated and tolerable. Enrollment is ongoing.

6 months ago

Combination therapy

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)

IDH1 mutation • IDH2 mutation

Venclexta (venetoclax) • Tibsovo (ivosidenib) • Idhifa (enasidenib) • Inqovi (decitabine/cedazuridine)

6ms

Drug Development for Leukemia : Comprehensive Analysis of Clinical Trial Success Rates Presented at the American Society Hematology (ASH) Annual Meetings (ASH 2023)

During the study period, CT assessing Enasidenib as monotherapy for R/R AML with IDH2 mutation, Ponatinib for CML and Philadelphia chromosome (Ph+) ALL, and Venetoclax for R/R CLL transitioned directly from Phase 2 to FDA approval. CT success rates for hematologic malignancies improved modestly over the last years. The high investment in CT for AML and CLL management has not resulted in increased approval rates proportional to reported CT.

6 months ago

Clinical

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Venclexta (venetoclax) • Iclusig (ponatinib) • Idhifa (enasidenib)

6ms

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%.

6 months ago

Clinical

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 R140 • IDH2 R172

Tibsovo (ivosidenib) • Idhifa (enasidenib)

6ms

Mitochondrial Isocitrate Dehydrogenase Inhibition Enhances CAR T-Cell Function By Restraining Antioxidant Metabolism and Histone Acetylation (ASH 2023)

To identify mitochondrial components that affect the long-term efficacy of CAR T-cells, we performed an in vitro screening using a mitochondria-related compound library based on the enrichment of the CD62L+ CAR T-cell subset, which mainly contains T memory stem cells (TSCM) and central memory T cells (TCM). Among several candidate compounds that promoted memory CAR T-cell formation, enasidenib (ENA), an inhibitor of both wild-type and mutant IDH2 enzymes, was the most effective one. The proportion of CD62L has increased by over 20%.

6 months ago

CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker • Epigenetic controller

IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • GZMB (Granzyme B) • SELL (Selectin L)

IDH2 mutation • LAG3 expression • HAVCR2 expression

Idhifa (enasidenib)

6ms

Decitabine/Cedazuridine (ASTX727) Combined with a Molecularly-Targeted Agent (Venetoclax, Gilteritinib, Ivosidenib, or Enasidenib) As Personalized Maintenance Therapy in Acute Myeloid Leukemia: First Results from a Phase 1b Study (ASH 2023)

Currently, oral azacitidine (CC-486) is the only drug approved in the maintenance setting in patients with AML who are unable to complete standard therapy...Patients having received either intensive induction (at least 2 cycles of therapy based on intermediate to high dose cytarabine) or low-intensity induction (at least 3 cycles based on low-dose cytarabine or a hypomethylating agent) were permitted... A fully oral, targeted maintenance regimen is feasible in AML. Early results show encouraging RFS and OS. Further enrollment and follow-up are required to better assess the safety and efficacy of these regimens.

6 months ago

Clinical • P1 data

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2)

Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • Tibsovo (ivosidenib) • Idhifa (enasidenib) • Inqovi (decitabine/cedazuridine) • Onureg (azacitidine oral)

6ms

The Cytogenetic and Molecular Testing Landscape in Patients with Newly Diagnosed Acute Myeloid Leukemia in Routine Clinical Practices in the United States (ASH 2023)

Tx for patients (pts) with actionable IDH1, IDH2, or FLT3 mutations includes Venetoclax (Ven)-based regimens (i.e. Ven+hypomethylating agents [HMAs] and Ven+low-dose cytarabine), HMA monotherapy (i.e. Azacitidine [Aza] or decitabine), and targeted Tx (i.e. ivosidenib±Aza, enasidenib±Aza, sorafenib±HMAs, and gilteritinib+Aza). This study found that cytogenetic and molecular testing have been integrated into routine clinical care settings for pts with ND AML receiving 1L Tx. The consistent testing rates in recent years, common use of NGS molecular testing technique, and the majority of pts having first specimen collected for molecular testing prior to 1L Tx initiation reflect physicians' intention to leverage molecular data to better inform Tx decisions. The subset of pts with second specimen collected for molecular testing after 2 weeks of 1L Tx initiation suggests some physicians' efforts to evaluate new and/or persistent targeted stable mutations.

6 months ago

Clinical

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

FLT3 mutation

Venclexta (venetoclax) • sorafenib • cytarabine • Xospata (gilteritinib) • azacitidine • decitabine • Tibsovo (ivosidenib) • Idhifa (enasidenib)

6ms

Phase 1b/2 Trial of Enasidenib in Lower-Risk MDS and Nonproliferative CMML without Isocitrate Dehydrogenase Type 2 Mutations (ASH 2023)

Prior treatment with ESA, G-CSF, and luspatercept was allowed with a 30-day washout period...One grade 4 event occurred (duodenal hemorrhage) in a patient with history of duodenal ulcers and concurrent aspirin use... Enasidenib at 200mg dose was safe and well tolerated in patients with lower-risk MDS. Thus far, one patient has seen trilineage improvement in blood counts and continues on study. The Phase 2 portion of the study is ongoing to further characterize safety and evaluate for efficacy to improve anemia and decrease transfusion needs.

6 months ago

P1/2 data

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD34 (CD34 molecule)

IDH2 mutation • IDH wild-type

Idhifa (enasidenib) • Reblozyl (luspatercept-aamt) • aspirin

6ms

I-DATA Study: Randomized, Sequential, Open-Label Study to Evaluate the Efficacy of IDH Targeted/Non- Targeted Versus Non-Targeted/IDH-Targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated Adult AML Patients Not Candidates for Intensive Induction Therapy (ASH 2023)

Similarly, the changes brought about in methylation due to IDH mutations in the AML genome have ushered in treatment regimens of venetoclax with hypomethylating agents...Patients randomized to first-line IDHi will receive Ivosidenib 500mg po orally daily on Days 1-28 (IDH1) or Enasidenib 100mg po orally daily on Days 1-28 (IDH2), each of 28-day cycle...Longitudinally embedded, comprehensive correlative studies will provide integrated genomic profiling of the leukemic clone during different disease stages and assess for potential resistance mutations or clonal evolution that may be predictors of relapse in this difficult to treat patient population. In addition, ultra-sensitive measurable-residual disease testing (ctDNA) and single-cell based combined transcriptional and mutational profiling will complement the detailed assessment.

6 months ago

Clinical

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Venclexta (venetoclax) • Tibsovo (ivosidenib) • Idhifa (enasidenib)

6ms

Development of a Fully Immunocompetent Adoptive Transfer In Vivo Model of Npm1cA; Idh2R140Q; Flt3ITD AML (ASH 2023)

Mice received daily oral gavage of either vehicle, 100 mg/kg venetoclax (BCL2 inhibitor), 100 mg/kg enasidenib (IDH2 inhibitor) or 30 mg/kg gilteritinib (FLT3 inhibitor). Adoptive transfer of splenocytes into either immunodeficient NCG or fully immunocompetent PepBoy recipients faithfully recapitulates the disease of primary mice in a reproducible manner. This model therefore provides an in vivo model conducive to drug development studies and provides the opportunity to understand the impact of both AML development and therapeutics on the normal immune system.

6 months ago

Preclinical • IO biomarker

FLT3 (Fms-related tyrosine kinase 3) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)

FLT3-ITD mutation • IDH2 R140Q

Venclexta (venetoclax) • Xospata (gilteritinib) • Idhifa (enasidenib)

6ms

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.

6 months ago

Clinical • P1/2 data • Combination therapy • IO biomarker

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation • IDH2 R172K • IDH2 R140Q • IDH2 R140 • IDH2 R172

Venclexta (venetoclax) • azacitidine • Idhifa (enasidenib)

6ms

IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation (clinicaltrials.gov)

P1, N=23, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed

6 months ago

Trial completion • Tumor mutational burden

TMB (Tumor Mutational Burden) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HLA-B (Major Histocompatibility Complex, Class I, B)

IDH2 mutation • IDH2 R140 • IDH2 R172

Idhifa (enasidenib)

6ms

A Randomized Phase II trial of C-DEC Venetoclax and Enasidenib Compared with Azacitidine and Venetoclax for Newly Diagnosed Older Adults with IDH2 mutant AML: A myeloMATCH Treatment Trial. (SWOG-Fall 2023)

No abstract available

6 months ago

Clinical • P2 data

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH2 mutation

Venclexta (venetoclax) • azacitidine • Idhifa (enasidenib)