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

Real-World Data Show Activity With Ivosidenib in IDH1+ Cholangiocarcinoma (Cancer Network) - P3b | N=220 | ProvIDHe (NCT05876754) | Sponsor: Servier Affaires Médicales | "Real-world data from the phase 3b ProvIDHe study (NCT05876754) demonstrated preliminary activity in patients with cholangiocarcinoma harboring IDH1 mutations who received Ivosidenib (Tibsovo), according to a presentation at the 2025 ESMO Gastrointestinal Cancers Congress. Initial data from ProvIDHe revealed that the median progression-free survival (PFS) in the full analysis set (n = 262) was 4.7 months (95% CI, 3.5-5.7). The 3-, 6-, and 12-month PFS rates were 64.2%, 40.1%, and 28.2%, respectively. Additionally, the median overall survival (OS) was 15.5 months (95% CI, 12.7-not evaluable [NE]). The 3-, 6-, and 12-month OS rates were 88.3%, 80.3%, and 60.0%, respectively."

P3 data • Real-world • Cholangiocarcinoma

Advancing AML Treatment: Evidence-Based Regimens and Guideline Updates for Targeted Treatments in R/R AML [Podcast]. (PubMed, Blood Lymphat Cancer) - "IDH1-inhibitors, such as ivosidenib and olutasidenib, block this aberrant metabolic pathway, allowing for differentiation and apoptosis of leukemia cells. Given the rarity of these mutations, comprehensive molecular testing remains essential to optimize therapeutic decision-making."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

Deep Dive into Targeted Therapies: Understanding IDH1-Mutant AML Treatments [Podcast]. (PubMed, Blood Lymphat Cancer) - "The results obtained from these clinical trials provide evidence that integrating oral targeted agents into the management of relapsed or refractory AML improves patient outcomes, especially for older or unfit patients who cannot undergo intensive chemotherapy. In conclusion, the episode demonstrates that the evolving use of IDH1 inhibitors, supported by rigorous clinical evidence, represents a promising advance in AML treatment by offering more precise, effective, and tolerable therapeutic options."

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

Patient characteristics, molecular testing, and treatment patterns of patients with cholangiocarcinoma in the United States: Focus on mIDH1 patients (ESMO-GI 2025) - "91.5% received 1L systemic therapy, including gemcitabine-cisplatin (GemCis) (33.3%) or GemCis-durvalumab (24.0%). 78.7% received 2L therapy including ivosidenib (IVO) (37.3%), GemCis (11.9%) or FOLFOX (5.1%). 67.8% received 3L therapy including IVO (27.5%), FOLFOX (15.0%), FOLFIRI (7.5%) or GemCis-durvalumab (7.5%). These real-world data indicate that pts with CCA were mostly diagnosed with advanced or metastatic disease... These real-world data indicate that pts with CCA were mostly diagnosed with advanced or metastatic disease. The majority of pts had access to molecular testing performed on tissue at diagnosis. The incidence of mIDH1 CCA reported is consistent with literature."

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

Ivosidenib for IDH1-mutant intrahepatic cholangiocarcinoma: Insights from a multicenter real-world study (ESMO-GI 2025) - "This study confirms that ivosidenib is a valid option for patients affected by metastatic IDH1 mutant CCA after at least one line of standard treatment."

Clinical • Real-world • Real-world evidence • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1

Molecular profiling success in advanced cholangiocarcinoma (CCA) based on tumour acquisition method (ESMO-GI 2025) - "Median survival from diagnosis of pts who received targeted treatment with pemigatinib (N=4) or ivosidenib (N=3) was 21.6 mo (95% CI 19.6-22.6); 8.8 mo (95% CI 5.7-14.4) for those on other active palliative treatment (HR=0.3, 95% CI 0.09 – 0.96, P = .04) and 5.2 mo (95% CI 2.6-7.4) for BSC (median follow-up: 7.4 mo). FNB or percutaneous biopsy offered best chance of molecular profiling success in those fit for active treatment. FNB or percutaneous biopsy offered best chance of molecular profiling success in those fit for active treatment. Molecular profiling was unsuccessful in one sixth due to inadequate tissue. Pts with identified alterations receiving targeted treatment had favourable survival, highlighting importance of tissue adequacy from initial diagnostic method."

Metastases • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2 • IDH1 • NTRK

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

Ivosidenib in pretreated Japanese (JPN) patients (pts) with mutant isocitrate dehydrogenase 1 (mIDH1) nonresectable/metastatic cholangiocarcinoma (n/mCCA): Phase II study results (ESMO-GI 2025) - P2, P3 | "IVO showed clinical benefit in JPN pts, mainly through disease stabilization, with PFS outcomes similar to ClarIDHy. IVO was well tolerated and no new safety signals were identified. Results support IVO as a safe and effective therapy for JPN pts with mIDH1 n/mCCA."

Clinical • Metastases • P2 data • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1

management of an adrenal cortical carcinoma induced non-islet cell tumor hypoglycemia: a case report (ENDO 2025) - "She was started on adjuvant mitotane, and chemotherapy (cisplatin, etoposide, and doxorubicin) which induced cardiomyopathy...Osilodrostat was initiated for Cushing syndrome...Patient had recurrent severe hypoglycemic episodes, which were refractory to increasing carbohydrate intake, high-dose prednisone, and octreotide...She also received pasireotide 60mg and diazoxide 5mg/kg every 8 hours...Upon applying for alpelisib approval, her clinical status rapidly declined, and she died after 3 months of NITCH diagnosis...IGF2-mediated hypoglycemia was refractory to numerous therapeutic interventions, including paseriotide, pembrolizumab, olaparib, ivosidenib, and cabozantinib. This case emphasizes rare manifestations of metastatic ACC and limitations of existing medical therapies for NITCH."

Case report • Clinical • Adrenal Cortex Carcinoma • Cardiomyopathy • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hypoglycemia • Metabolic Disorders • Oncology • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • IGF1 • IGF2

A placebo controlled study to compare ivosidenib or enasidenib in patients with newly diagnosed acute myeloid leukemia or myelodysplastic syndrome. (ANZCTR) - P3 | N=968 | Active, not recruiting | Sponsor: HOVON (the Haemato Oncology Foundation for Adults in the Netherlands) | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IDH1 • IDH2

PIVOT: Prospective Evaluation of Ivosidenib Maintenance Following Allogeneic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Neoplasia With IDH1 (Isocitrate Dehydrogenase 1) Mutation (clinicaltrials.gov) - P2 | N=76 | Recruiting | Sponsor: Technische Universität Dresden | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2025 ➔ Jun 2025

Enrollment open • Trial initiation date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Ivosidenib + mFOLFIRINOX in Patients With Resectable Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=16 | Suspended | Sponsor: Case Comprehensive Cancer Center | Recruiting ➔ Suspended

Trial suspension • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

FDA Approval Summary: Ivosidenib for Treatment of Adult Patients with Relapsed/Refractory Myelodysplastic Syndrome with an IDH1 Mutation. (PubMed, Clin Cancer Res) - "Serious adverse reactions in ≥5% included differentiation syndrome, fatigue, and rash. The most common (≥20%) adverse reactions were arthralgia, fatigue, cough, diarrhea, decreased appetite, mucositis, myalgia, and pruritis."

FDA event • Journal • Cough • Fatigue • Hematological Malignancies • Mucositis • Musculoskeletal Pain • Myelodysplastic Syndrome • Oncology • Pain • Pruritus • Respiratory Diseases • IDH1

Paracrine and Neoplastic Effects of D-2HG (EACR 2025) - "This study aims to elucidate 2-HG's targets, proposing strategies to enhance clinical outcomes by minimizing 2-HG levels and uncover new pathways that, when inhibited, could increase ivosidenib efficacy."

Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1

VENETOCLAX IN COMBINATION WITH CYTARABINE AND ACTINOMYCIN D (ACTIVE) FOR RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2025) - "Venetoclax exposure was confirmed in 13% (14/107) of cases, and 25 % (26/107) had relapsed after a previous alloSCT.Gilteritinib, trametinib, ivosidenib, ponatinib, and dasatinib were added to ACTIVE in 22 % (23/107), 4 % (4/107), 2 % (2/107), 1 % (1/107), and 1 % (1/107), respectively.The ORR was 78 % (82/105), and the CRc rate was 62 % (65/105) with 45 % (29/65) achieving MRD negativity. ACTIVE-based salvage treatment demonstrates promissing antileukemic efficacy with a high bridge-to-alloSCT rate in R/R AML."

Combination therapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

EFFICACY AND OUTCOMES OF NOVEL THERAPEUTIC AGENTS AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL THERAPY IN MYELODYSPLASTIC SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Newer agents included Rigosertib (41%, n=312/770), Imetelstat (15%, n=118/770), Pembrolizumab (8%, n=65/770), Enasidenib (9%, n=67/770), and Sabatolimab (7%, n=53/770) Ivosidenib (6%, 45/770), Elritercept 2%, n=15 /770), Pevonedistat (3%, 21/770), Emavusertib (2%, 15/770), Atezolizumab (6%, 46/770), and Olutasidenib (2%, n=13/770). The most commonly used conventional agent was azacitidine (19%, n= 147/770)... This study highlights promising results with the investigational agents for MDS. However, large studies with more power are needed to strengthen our understanding of these investigational agents in MDS patients."

Combination therapy • Monotherapy • Retrospective data • Review • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

Effect of the IDH1 inhibitor combined with hypomethylating agents on acute myeloid leukemia. (PubMed, Tumori) - "The IDH1 inhibitor with HMAs suppressed IDH1R132H-MOLM-13 cell proliferation and viability and decreased the methylation level by repressing the phosphorylation of the PI3K/AKT pathway, showing a synergistic inhibitory effect."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • DNMT1 • IDH1

PHASE 3 STUDY OF EITHER IVOSIDENIB MONOTHERAPY OR AZACITIDINE MONOTHERAPY IN PATIENTS WITH IDH1 MUTANT MYELODYSPLASTIC SYNDROMES WHO ARE HYPOMETHYLATING AGENT NAIVE (PYRAMIDH) (EHA 2025) - P3 | "Key secondary endpoints include duration of CR+PR per IWG 2006 criteria, time to CR+PR per IWG 2006 criteria, transfusion independence rate, AML transformation rate, and number of patients going to transplant. Other secondary endpoints are CR+PR at 6 months per IWG 2006 criteria; CR+PR at 4 and 6 months per IWG 2023 criteria; overall response rate per IWG 2023 criteria, duration of response, EFS, OS, duration of transfusion independence (TI), time to TI, AML transformation, quality of life, PK/PD, and safety."

Clinical • Monotherapy • P3 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IDH1

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

MATCHING-ADJUSTED INDIRECT COMPARISON (MAIC) OF OLUTASIDENIB (OLU) AND IVOSIDENIB (IVO) IN ISOCITRATE DEHYDROGENASE 1 (IDH1)-MUTATED RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML) (EHA 2025) - "Given the rarity of IDH1mut R/R AML patients, prospective trials comparing these IDH1 inhibitors are unlikely to be performed.Aims: In the absence of a head-to-head trial, an MAIC was performed to estimate relative treatment effects of OLU vs. IVO in IDH1mut R/R AML.Analyses used registrational data for OLU (Study 2102-HEM-101; N=147; individual-level data) and IVO (AG120-C-001; N=174; study-level data). Naïve and adjusted rates of response for OLU vs. IVO were comparable (adjusted point estimate favored OLU for CR and IVO for CR+CRh), while a longer duration of CR+CRh was observed with OLU. Adjusted OS was similar between the two groups, although the HR favored OLU, and could not be estimated by response category given lack of patient characteristics and reduction in effective sample size (ESS)."

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

COMPARATIVE EFFECTIVENESS OF OLUTASIDENIB AND IVOSIDENIB IN MIDH1 RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA PATIENTS POST-VENETOCLAX: INSIGHTS FROM 2102-HEM-101 AND A REAL-WORLD EXTERNAL CONTROL (EHA 2025) - "This study suggests OLU has favorable effectiveness versus IVO for patients in mIDH1 AML patients R/R to a VEN-based regimen. As with any RW-ECA study, limitations include the risk of unmeasured confounding and differential outcome reporting."

Clinical • HEOR • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1

IVOSIDENIB COMBINED WITH VENETOCLAX AND AZACITIDINE FOR THE TREATMENT OF NEWLY DIAGNOSED IDH1-MUTANT ACUTE MYELOID LEUKEMIA: A PROSPECTIVE, TWO COHORTS, MULTICENTER STUDY (EHA 2025) - "Previous data showed that the multi-drug combination regimen of IVO demonstrates good tolerability and efficacy. This study will be the first to clarify the feasibility of multi-drug regimens in the treatment of IDH1m AML patients in China, providing ideas and evidence to improve the prognosis of Chinese IDH1m AML patients."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • IDH1

COMPENSATORY KDM4 UPREGULATION IN IDH2-MUTANT AMLS REPRESENTS A THERAPEUTIC VULNERABILITY IN ENASIDENIB-SENSITIVE PATIENTS (EHA 2025) - "Despite the development of targeted therapies (ivosidenib for IDH1mut and enasidenib (ENA) for IDH2mut), resistance is common and often leads to relapse, underscoring the urgent need for new therapeutic strategies. Altogether, our data reveal that IDH2mut AMLs exhibit a compensatory upregulation of KDM4 proteins, possibly due to 2-HG-mediated inhibition, creating a potential therapeutic vulnerability in ENA-sensitive IDH2mut AMLs. Better understanding the mechanisms behind IDH2mut and ENA resistance is important to further improve patient risk stratification and outcomes."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • IDH1 • IDH2 • ITGAM

Molecular profiling in targeted therapy of gliomas in a community setting. (ASCO 2025) - "Accordingly, 11 patients received targeted therapy: 3 patients olaparib (RAD51C, BRCA2, H3.3 G34), 2 pembrolizumab (TMB high), 1 ivosidenib (IDH1), 1 selumetinib (NF1), 1 alpelisib (PIK3CA), 1 erdafitinib (FGFR3), 1 trametinib (NF1) and 1 dabrafenib/trametinib (BRAF) and then everolimus (TSC2). Molecular profiling nowadays is not only mandatory in glioma classification but can also provide additional therapies in patients with limited options."

IO biomarker • Tumor mutational burden • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • High Grade Glioma • Oligodendroglioma • Oncology • Solid Tumor • ATRX • BRAF • BRCA2 • EGFR • FGFR3 • IDH1 • MSI • NF1 • PD-L1 • PIK3CA • PTEN • RAD51C • TERT • TMB • TP53 • TSC2

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