Tibsovo (ivosidenib) / CStone Pharma, Servier, Schrodinger, Sagard Healthcare - LARVOL DELTA

Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. (PubMed, N Engl J Med) - P3 | "Ivosidenib and azacitidine showed significant clinical benefit as compared with placebo and azacitidine in this difficult-to-treat population. Febrile neutropenia and infections were less frequent in the ivosidenib-and-azacitidine group than in the placebo-and-azacitidine group, whereas neutropenia and bleeding were more frequent in the ivosidenib-and-azacitidine group. (Funded by Agios Pharmaceuticals and Servier Pharmaceuticals; AGILE ClinicalTrials.gov number, NCT03173248.)."

Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • IDH1

Preliminary efficacy outcomes of ivosidenib in patients with IDH1-mutated cholangiocarcinoma (mIDH1 CCA): Initial results from the phase IIIb ProvIDHe study (ESMO-GI 2025) - P3 | "Median number of prior systemic regimens was 2, mainly gemcitabine + cisplatin alone (40.1%), or with immunotherapy (42%). This analysis focused on the initial efficacy of IVO in the ProvIDHe study, encompassing the largest cohort of patients with mIDH1 CCA treated in a real-world setting. These findings corroborate the efficacy observed in the ClarIDHy trial, reinforcing the therapeutic potential of IVO. The study is still ongoing, and future analyses will consolidate these results."

Clinical • IO biomarker • P3 data • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1

Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML. (PubMed, Blood Adv) - P3 | "These long-term efficacy and safety results confirm the benefit of ivosidenib-azacitidine in this challenging-to-treat population and support its use as a standard of care with the longest reported survival benefit for intensive chemotherapy-ineligible patients with IDH1-mutated AML. ClinicalTrials.gov registration ID: NCT03173248."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • IDH1

Updated response and safety analyses from a Phase 1 study of ivosidenib combined with intensive chemotherapy in patients with newly diagnosed (ND) Acute Myeloid Leukemia with isocitrate dehydrogenase (IDH)1 mutation (ASH 2025) - P1, P3 | "Introduction Ivosidenib (IVO) is approved as monotherapy and in combination with azacitidine for frontline treatmentof patients (pts) with mIDH1 acute myeloid leukemia (AML) unfit for intensive chemotherapy (chemo)...Pts with ND mIDH1AML received induction therapy: cytarabine 200 mg/m2/d × 7 d and either daunorubicin 60 mg/m2/d oridarubicin 12 mg/m2/d × 3 d (up to 2 cycles of induction were permitted) and IVO 500 mg once dailystarting on d 1 of induction therapy...IVO maintenance has an acceptable safety profile, is associated with stablenormalization of blood counts, and results in durable responses and long-term survival acrosscomutational profiles. The benefit of this frontline regimen is being assessed in a phase 3 randomized,blinded trial (NCT03839771)."

Clinical • P1 data • Acute Kidney Injury • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Neutropenia • Renal Disease • Thrombocytopenia • TP53

Lessons from Exceptional Responders with High-Grade Brain Tumors Treated with Precision Targeted Therapies. (PubMed, J Immunother Precis Oncol) - "Standard-of-care surgery, radiation, and temozolomide yield a median survival of 14-16 months in patients with glioblastoma (GBM)...NGS yielded actionable alterations targeted after conventional surgery/chemoradiation therapy: imatinib (for KIT and PDGRA amplification) and bevacizumab (for KDR [VEGFR2] amplification); everolimus (mTOR inhibitor for TSC2 and PTEN loss-of-function alterations); and ivosidenib (IDH1 inhibitor for IDH1 mutations in two cases, including the oligosarcoma). Three patients remain in radiographic and clinical remission at 39+, 48, and 52+ months; the patient with oligosarcoma showed clinical and imaging response lasting 8 months. Our exceptional responders with high-grade gliomas suggest that biomarker-matched targeted therapy can benefit select patients with high-grade glioma and warrants prospective clinical trials."

Journal • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Sarcoma • Solid Tumor • IDH1 • KDR • PTEN • TSC2

Breast cancer tumor immune microenvironment landscape identifies prognostic risk genes and potential drugs. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "Furthermore, fourteen candidate drugs targeting this network were predicted, and structural analogs of Lumacaftor and Ivosidenib showed promising docking affinities to CD1C and CXCR3, respectively. These findings provide preliminary insights into TIM-associated prognostic pathways and suggest candidate compounds for further investigation in BRCA."

Journal • Breast Cancer • Oncology • Solid Tumor • BRCA • CD1C • CD40LG • CD69 • CXCR3

Differentiation Syndrome in Acute Myeloid Leukemia: Molecular Mechanisms, Clinical Spectrum, and Emerging Therapeutic Paradigms. (PubMed, Int J Mol Sci) - "While differentiation therapy revolutionized acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), its extension into non-APL AML has been limited until recent targeted agents...IDH1/2 inhibitors (ivosidenib, enasidenib, olutasidenib) yield overall response rates (ORRs) of 30-94% in AML with DS in 10-19%. Menin inhibitors (revumenib, ziftomenib, enzomenib, bleximenib) achieve ORRs of 33-88% in KMT2A-rearranged or NPM1-mutated AML, with DS in 10-25% and QT prolongation as key toxicities. FLT3 inhibitors (gilteritinib, quizartinib) improve survival in FLT3-mutated AML with DS in 1-5%...Improved recognition of DS and rational combination approaches will be essential to maximize the therapeutic benefit. Future research should address mechanisms of resistance and biomarkers to achieve cures beyond APL."

Journal • Review • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • IDH1 • IDH2 • KMT2A • NPM1

A PHASE IB/2 TRIAL OF AN ALL-ORAL "TRIPLET" REGIMEN FOR IDH-MUTATED MYELOID MALIGNANCIES: DECITABINE/CEDAZURIDINE AND VENETOCLAX IN COMBINATION WITH IVOSIDENIB/ENASIDENIB (EHA 2025) - P1/2 | "An all-oral triplet regimen of DEC-C+VEN+IVO/ENA demonstrated an impressive CRc rate in both ND and R/R pts with IDH mutant myeloid neoplasms with no new safety signals."

Combination therapy • Acute Myelogenous Leukemia • Hepatology • Infectious Disease • Myelodysplastic Syndrome • IDH1 • IDH2 • TP53

Impact of ivosidenib on Tumor Growth Rate in patients with chemotherapy-resistant and IDH-1 mutated advanced cholangiocarcinoma (ESMO Asia 2025) - P3 | "These preliminary results show that Ivosidenib achieved a significant decrease in TGR in chemotherapy-resistant pts with IDH1-mutant advanced CCA. Measuring TGR could overcome some of the challenges faced at time of analysing response with cytostatic agents, which mainly trigger disease stabilisation by RECIST 1.1. More investigations are needed to fully determine of the use of TGR in this context."

Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1

Efficacy of vorasidenib in patients with IDH-mutant gliomas previously treated with ivosidenib (ESMO-TAT 2026) - "Treatments received prior to ivosidenib included surgical resection (23, 79%), radiation (16, 55%), temozolomide (15, 52%), PCV (4, 14%) bevacizumab (3, 10%), lomustine (2, 7%) and pembrolizumab (1, 3%). Vorasidenib demonstrated clinical efficacy and tolerability in patients with IDH-mutant gliomas previously treated with ivosidenib. Notably, patients who transitioned due to FDA approval or toxicity maintained disease stability, while a subset of those with progression on ivosidenib achieved stabilization with vorasidenib. These findings support vorasidenib as a viable therapeutic option following ivosidenib exposure."

Clinical • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1

A Study of an IDH1m Inhibitor in Participants With IDH1-Mutated Malignancies and Hepatic or Renal Impairment (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Servier Bio-Innovation LLC

New P1 trial • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Renal Disease • IDH1

The allosteric IDH1 inhibitor ivosidenib overcomes chemoresistance in intrahepatic cholangiocarcinoma models expressing wild-type IDH1. (PubMed, J Clin Invest) - "Gemcitabine-based chemotherapy is the standard treatment regime for advanced intrahepatic cholangiocarcinoma (iCCA), but the frequent presence of chemoresistance limits its efficacy. The low level of Mg2+, an ion that competitively hinders binding of ivosidenib on wtIDH1, in iCCA tumor microenvironment contributed to the expanded therapeutic window of ivosidenib in patients with iCCA. Our work revealed the potency of combining targeting IDH1 and chemotherapy against wtIDH1 iCCA and other tumors."

Journal • Biliary Cancer • Cholangiocarcinoma • Gene Therapies • Hepatology • Liver Cancer • Oncology • Solid Tumor • IDH1

Pharmacologic wtIDH1 inhibition remodels the PDAC immune landscape and improves checkpoint blockade efficacy (AACR 2026) - "Our earlier work identified that AG-120 (Ivosidenib), an FDA-approved inhibitor of mutant IDH1, also inhibits wild-type IDH1 (wtIDH1) under nutrient-restricted conditions typical of PDAC... wtIDH1 inhibition offers a dual benefit in PDAC by impairing tumor metabolism and promoting immune activation. This metabolic-immune reprogramming provides a strong rationale for combining wtIDH1 inhibitors with existing immunotherapies."

Checkpoint block • Checkpoint inhibition • Clinical • IO biomarker • Oncology • Pancreatic Ductal Adenocarcinoma • CD8 • IDH1 • PTPRC

Prognostic impact and clinical characteristics of KRAS mutations and CDKN2A loss in IDH1-mutant intrahepatic cholangiocarcinoma (AACR 2026) - "Background: In the ClarIDHy trial, ivosidenib significantly improved progression-free survival (PFS) compared with placebo in patients with previously treated IDH1-mutant cholangiocarcinoma (CCA) and is currently awaiting insurance approval in Japan... IDH1 mutations less frequently co-occur with KRAS mutations and CDKN2A loss. IDH1-mutant iCCA without these co-alterations exhibited favorable clinical outcomes and distinct radiopathological characteristics, highlighting the biological heterogeneity associated with genomic co-alterations in IDH1-mutant iCCA."

Clinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CDKN2A • IDH1 • KRAS

IDH1 inhibition potentiates gemcitabine efficacy in pancreatic ductal adenocarcinoma (AACR 2026) - "This study provides mechanistic insight into how AG-120 overcomes gemcitabine resistance in PDAC cells by targeting wt-IDH1 and modulating the OXPHOS pathway, highlighting a potential therapeutic strategy to improve treatment outcomes."

Clinical • Oncology • Pancreatic Ductal Adenocarcinoma • IDH1 • TRPM7

Targeting cytosolic mutant IDH1 by hyperactivation to induce cancer cytotoxicity (AACR 2026) - "Although FDA-approved inhibitors such as ivosidenib and enasidenib effectively suppress 2HG, fewer than half of patients respond, and resistance invariably develops. In parallel, we found that activation of mitochondrial 2HG production in IDH1-mutant cancer cells triggers profound metabolic collapse, leading to impaired cell growth in vitro and in vivo. Together, these results suggest that direct or indirect hyperactivation of the mutant IDH1 pathway may represent a new therapeutic strategy --- targeting cytosolic IDH1 mutations by driving cancer cells beyond their metabolic limits."

Acute Myelogenous Leukemia • Brain Cancer • Glioma • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • IDH1 • IDH2

Isocitrate dehydrogenase (IDH) isoform switch confers resistance to ivosidenib in myelodysplastic neoplasm (AACR 2026) - "Abstract is embargoed at this time."

Late-breaking abstract • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Therapy and malignant progression reshape the splicing landscape to generate shared, tumor-wide neoantigens in IDH-mutant gliomas (AACR 2026) - "We investigate these effects in IDH-mutant gliomas to identify conserved, upregulated, and potentially targetable splice-derived neoantigens. Paired bulk RNA-seq data from primary and recurrent IDH-mutant gliomas were obtained from the UCSF Brain Tumor Center patient data and AG-120-treated glioma cell line data (Wu et al., Science 2025)... We show that therapy and malignant progression remodel the splicing landscape of IDH-mutant gliomas via altered splicing regulator expression. Moreover, this remodeling produces conserved, tumor-wide, and putatively immunogenic NJs."

IO biomarker • Tumor mutational burden • Tumor-specific neoantigens • Brain Cancer • Glioma • Oncology • Solid Tumor • EEF1A1 • GNAS • HLA-A • IGF2BP3 • PTPRZ1 • RANBP2 • TMB

Wild-type IDH1 inhibition induces homologous recombination deficiency and enhances PARP inhibitor sensitivity in pancreatic cancer (AACR 2026) - P1 | "Effects of IDH1 inhibition (ivosidenib) and PARP inhibition (olaparib), alone and combined, were evaluated in vitro through cell viability, apoptosis, and DNA damage assays. Our findings reveal a novel role for wtIDH1 in maintaining homologous recombination in PDAC. Inhibition of wtIDH1 functionally induces HR deficiency in HRP tumors, sensitizing them to PARP inhibition. This combination represents a promising therapeutic approach for the majority of PDAC patients lacking canonical HR mutations and warrants further translational development."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA • HRD • IDH1

A ketogenic diet sensitizes pancreatic cancer to metabolic therapies (AACR 2026) - "We demonstrate that combining glutamine metabolism inhibitors, such as CB839 or 6-diazo-5-oxo-L-norleucine (DON), with a KD leads to robust anti-tumor effects in preclinical models of pancreatic cancer. Together, these findings demonstrate that a ketogenic diet exposes a metabolic and redox vulnerability in PDAC by increasing reliance on glutamine-driven anaplerosis and elevating intratumoral ROS. Exploiting this state with targeted metabolic inhibitors—alone or in combination with ROS-inducing agents—produces potent anti-tumor responses and highlights a promising therapeutic strategy for pancreatic cancer."

Oncology • Pancreatic Cancer • Solid Tumor

Νοvel Therapies in High-Risk Myelodysplastic Syndromes. (PubMed, Eur J Haematol) - "Recent advances have led to the development of novel therapeutic strategies, such as BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, enasidenib), CD47 inhibitors (magrolimab), TIM-3 inhibitors (sabatolimab), XPO1 inhibitors (eltanexor), NEDD8-activating enzyme inhibitors (pevonedistat), TP53-targeted agents (eprenetapopt), liposomal chemotherapy (CPX-351), and oral HMA formulations. Combinations of hypomethylating agents with these new drugs, as first-line treatment, have to date not proven more efficacious than HMA monotherapy. This review summarizes the current therapeutic landscape on novel therapies for HR-MDS, highlighting their mechanism of action, efficacy, and demonstrates the unmet clinical need for more effective therapies."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HAVCR2 • IDH1 • IDH2

Outcomes of Frontline Triplet Regimens With a Hypomethylating Agent, Venetoclax, and Isocitrate Dehydrogenase Inhibitor for Intensive Chemotherapy-Ineligible Patients With Isocitrate Dehydrogenase-Mutated AML. (PubMed, J Clin Oncol) - P1/2 | "Given the excellent outcomes of IDH-triplet therapy for newly diagnosed, IC-ineligible IDH-mutant AML, further prospective studies comparing IDH-triplet versus IDH-doublet regimens are warranted."

Journal • Acute Myelogenous Leukemia • Transplantation • IDH1 • IDH2

SUBGROUP ANALYSIS OF THE GREATER CHINA REGION IN THE RANDOMIZED PHASE 3 AGILE STUDY OF IVOSIDENIB+AZACITIDINE VERSUS PLACEBO+AZACITIDINE IN PATIENTS WITH NEWLY DIAGNOSED MIDH AML (EBMT 2026) - P3 | "The data indicate that IVO+AZA provides significant therapeutic benefits for patients with newly diagnosed mIDH1 AML in the Greater China region with higher mOS, better hematologic responses, and faster blood count recovery, while maintaining a manageable safety profile vs PBO+AZA."

Clinical • P3 data • Acute Myelogenous Leukemia • IDH1

Budget Impact of Venetoclax for Newly Diagnosed Patients with Acute Myeloid Leukemia Aged ≥ 75 Years or with Comorbidities Precluding Intensive Chemotherapy in the United States. (PubMed, Adv Ther) - "Inclusion of venetoclax combinations for newly diagnosed patients with AML aged ≥ 75 years or with comorbidities precluding intensive chemotherapy reduced the budget impact, providing potential financial benefits for US payers."

HEOR • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase III study of ivosidenib vs placebo in isocitrate dehydrogenase 1 (IDH1)-mutant conventional chondrosarcoma (CHONQUER): Frequency of IDH1 mutation by clinical factors (Sarcoma-RC 2026) - P3 | "Legal entity responsible for the study Servier. Funding Servier."

Clinical • P3 data • Sarcoma • Solid Tumor • IDH1