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

CUPISCO: A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site (clinicaltrials.gov) - P2 | N=528 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2024

Trial completion • Trial completion date • Oncology

OncoKBTM, MSK's precision oncology knowledge base: 2024 updates (AACR 2025) - "OncoKB promoted BRAF fusions to Level 1 following inclusion as patient eligibility criteria in the FDA drug label for tovorafenib (low-grade glioma). Additionally, OncoKB included KRAS G12C in colorectal cancer and IDH1 mutations in myelodysplastic syndromes as Level 1 following FDA approval of adagrasib + cetuximab and ivosidenib, respectively...Lastly, novel biomarkers including FBXW7 and PPP2R1A alterations (endometrial and ovarian cancer), SMARCA4 mutations (non-small cell lung cancer and esophageal adenocarcinoma) and MTAP deletions (all solid tumors) were included in OncoKB based on compelling preclinical and emerging clinical evidence in association with lunresertib + camonsertib, PRT3789, and AMG193 and MRTX1719, respectively...OncoKB also implemented major software updates to support data integration into the EPIC platform. Future OncoKB efforts are focused on whole genome/exome curation, inclusion of biomarkers for non-NGS-based precision oncology therapies,..."

Tumor mutational burden • Brain Cancer • CNS Tumor • Colorectal Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Glioma • Hematological Malignancies • Lung Cancer • Microsatellite Instability • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Intestinal Carcinoma • Solid Tumor • BRAF • FBXW7 • IDH1 • KRAS • MSI • MTAP • POLD1 • PPP2R1A • SMARCA4 • TMB

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 • Hematological Disorders • Hypoglycemia • Metabolic Disorders • Oncology • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • IGF1 • IGF2

Preliminary efficacy outcomes of ivosidenib in patients with IDH1 mutated cholangiocarcinoma (mIDH1 CCA): initial results from the phase 3b ProvIDHe study (ESMO-GI 2025) - No abstract available

Clinical • 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 2 Study Results (ESMO-GI 2025) - No abstract available

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

Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights from a Multicenter Real-World Study (ESMO-GI 2025) - No abstract available

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

Real-world survival outcomes with ivosidenib in Chinese patients with IDH1-mutated intrahepatic cholangiocarcinoma. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

Effect of ivosidenib and vorasidenib on 2-hydroxyglutarate levels in low grade glioma: An in vivo MR spectroscopy study. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Preclinical • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Phase 3 study of either ivosidenib monotherapy or azacitidine monotherapy in patients with IDH1-mutant myelodysplastic syndromes who are hypomethylating agent naive (PyramIDH). (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06465953 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Monotherapy • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • IDH1

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). (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

Real world efficacy and safety of ivosidenib in US veterans with IDH1 mutated cholangiocarcinoma. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

A phase 1b/2, safety lead-in and dose-expansion trial of ivosidenib plus durvalumab and gemcitabine/cisplatin as first-line therapy in patients with locally advanced, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT06501625 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P1/2 data • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1

Phase 3 study of ivosidenib vs placebo in locally advanced or metastatic IDH1-mutant conventional chondrosarcoma untreated or previously treated with 1 systemic treatment regimen (CHONQUER). (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06127407 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P3 data • Oncology • Sarcoma • Solid Tumor • IDH1

Wild-type IDH1 inhibition induces BRCAness to sensitize pancreatic cancer to PARP inhibitors (AACR 2025) - "This study uncovers a novel strategy to target HR-proficient PDAC using combined IDH1 and PARP inhibition, demonstrating significant preclinical efficacy. Future studies will focus on optimizing and translating this approach into clinical practice."

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

Ivosidenib Confers BRCAness Phenotype and Synthetic Lethality to Poly (ADP-Ribose) Polymerase Inhibition in BRCA1/2-Proficient Cancer Cells. (PubMed, Biomedicines) - "This uncovers a novel, metabolism-independent mechanism of ivosidenib, repositioning it as a therapeutic agent for HRD tumors. These findings propose a strategy to expand PARPi eligibility to WT BRCA cancers, addressing a critical unmet need in oncology."

Journal • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD • RAD51 • YTHDC2

Budget Impact Analysis of Venetoclax Combination Therapies for the Treatment of Newly Diagnosed Acute Myeloid Leukemia Patients Who Are Aged 75 Years or Older, or Who Have Comorbidities That Preclude Use of Intensive Induction Chemotherapy (ISPOR 2025) - "The most up-to-date market share, reflecting the current treatment landscape projected venetoclax + azacitidine or decitabine to capture 53% and 15% market share, respectively, from existing treatments (azacitidine, low-dose cytarabine [LDAC], decitabine, ivosidenib, gemtuzumab ozogamicin, glasdegib + LDAC, and ivosidenib + azacitidine). Use of venetoclax combinations for the treatment of FDA-approved indication of ND AML reduced the budget impact and provides potential financial benefit for US payers."

Clinical • Combination therapy • HEOR • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Metabolism and therapy in acute myeloid leukemia with isocitrate dehydrogenase 1/2 mutations (PubMed, Med Sci (Paris)) - "Although the recent introduction of selective inhibitors of IDH1 (ivosidenib) and IDH2 (enasidenib) has improved the prognosis of patients with IDH1- and IDH2-mutant AML, several mechanisms of resistance to these treatments have already been identified, including metabolic reprogramming. The study of these mechanisms has opened up new therapeutic opportunities for the monitoring and treatment of patients with this subtype of AML."

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

First Report of NSCLC With IDH1 Mutation: A Case Report. (PubMed, Clin Lung Cancer) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IDH1

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs; approval of amivantamab plus lazertinib for non-small cell lung cancer, durvalumab for small cell lung cancer, tislelizumab for esophageal cancer, tisotumab vedotin for cervical cancer, ivosidenib for leukemia, and venetoclax for lymphoma in Japan. (PubMed, Int J Clin Oncol) - No abstract available

Japanese regulatory • Journal • Cervical Cancer • Esophageal Cancer • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Investigating druggability of myeloid and lymphoid lineage gene mutations in advanced phase CML by employing drug discovery tools: Implications in fatal blast crisis CML precision oncology (AACR 2025) - "We also found that some FDA-approved drugs for different hematological malignancies (e.g. VENETOCLAX, DECITABINE, AZACITIDINE, BORTEZOMIB, ZANUBRUTINIB, IVOSIDENIB, TAZEMETOSTAT, RUXOLITINIB, PACRITINIB, ARSENIC TRIOXIDE etc.) can effectively target multiple gene groups mutated in our advanced phase CML patients (Table 1-4, Figures 1-4). NGS analysis of AP- & BC-CML found mutations in many AML-/ALL-lineage genes, which is much higher than previously reported. NGS analysis of AP- & BC-CML found mutations in many AML-/ALL-lineage genes, which is much higher than previously reported. This shows a huge genetic similarity between BC-CML and AML/ALL. FDA-approved and various novel experimental drugs under clinical trials are available against some of the genes we reported."

IO biomarker • Metastases • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • AKT1 • BCL2 • DNMT3A • IDH1 • JAK2 • NPM1 • TET2

Circulating tumor DNA analysis demonstrates newly emerging alterations in previously treated IDH1 mutated cholangiocarcinoma patients enrolled in the ClarIDHy study (AACR 2025) - "Background: Ivosidenib (IVO) is a first-in-class oral inhibitor of the IDH1 mutant (mIDH) enzyme... Analyses of paired baseline/EOT samples suggest that multiple acquired mutations could contribute to IVO resistance, with oncogenic MAPK pathway alterations being the most common. Consistent with previous clinical studies conducted in AML, IDH1 second site mutations and isotype switching to IDH2, rarely emerge during IVO treatment. The lack of detectable mutations in the majority of patients could reflect the sensitivity of the NGS assay or a role for non-genetic mechanisms of resistance."

Circulating tumor DNA • Clinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • IDH1 • IDH2 • KMT2C • KRAS • MAP2K1 • NF1 • NRAS • WT1

Wildtype IDH1 blockade as a strategy to modulate the tumor microenvironment and boost immune responses in pancreatic cancer (AACR 2025) - "Previous work in our lab demonstrated the efficacy of ivosidenib, an FDA-approved inhibitor of mutant isocitrate dehydrogenase 1 (IDH1), also inhibits wild-type IDH1(wtIDH1) under conditions mimicking the PDAC TME...Our data demonstrates that IDH1 inhibition not only reduces cancer cell proliferation in vitro but alsoremodels the TME in in vivo, enhancing immune responsiveness. Modulation of the TME via IDH1 inhibition offers a promising avenue to improve efficacy of existing therapies, including chemotherapy and immune checkpoint inhibitors as a part of combination treatment strategies."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ANXA5 • CD8 • IDH1 • IL7R • PTPRC

A ketogenic diet sensitizes pancreatic cancer to inhibition of glutamine metabolism (AACR 2025) - "Ivosidenib and CB839 were used for combination therapies. A ketogenic diet induces a metabolic shift in pancreatic cancer, altering nutrient and metabolite levels in diverse in vivo models. A ketogenic diet demonstrates a robust anti-tumor effect in various pancreatic cancer mouse models, likely arising from the diminished glucose and increased fatty acid load inherent in the diet. Metabolic adaptation towards an oxidative phosphorylation (OXPHOS) phenotype makes pancreatic cancer especially susceptible to antioxidant and mitochondrial inhibitors, as well as inhibitors of glutamine-metabolizing enzymes."

Late-breaking abstract • Oncology • Pancreatic Cancer • Solid Tumor • IDH1 • SLC1A5

Debio 1562M, a 2ndgeneration ADC targeting CD37, shows high potency against AML and MDS and safe toxicological profile for future clinical development (AACR 2025) - "Debio 1562M activity was benchmarked against several targeted therapies such as menin, FLT3, IDH1 and IDH2 inhibitors or gemtuzumab ozogamicin (GO) CD33-targeting ADC, in different in vivo models. In MOLM-13 xenografted mice, Debio 1562M induced tumor regression after a single injection similarly to GO, while the menin inhibitor revumenib achieved tumor stasis with twice daily administrations and the FLT3 inhibitor gilteritinib only achieved partial response after daily administrations. Similarly, in 4 patient-derived xenograft models bearing FLT3, IDH1 or IDH2 mutations, Debio 1562M led to greater circulating blast reduction compared to gilteritinib, ivosidenib IDH1 inhibitor and enasidenib IDH2 inhibitor...On-target toxicity profile of Debio 1562M could not be evaluated due to lack of cross-reactive species, however no significant toxicity on human PBMCs was observed in vitro. In conclusion, the promising antitumor activity and tolerability of Debio 1562M in..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • CD37 • FLT3 • IDH1

Industry Educational Session - Management of mIDH AML: Practical implementation and experience- Sponsored by Servier (BSH 2025) - "Sponsored by Servier Details Overview of IDH mutations and management of AML AGILE data 2 real world case studies of the use of ivosidenib"

Acute Myelogenous Leukemia