138MO - Baseline characteristics and molecular testing of patients with IDH1-mutated cholangiocarcinoma: Initial results from the phase IIIb ProvIDHe study

Background

Ivosidenib (IVO) has demonstrated efficacy as an oral inhibitor of the protein encoded by the mutant isocitrate dehydrogenase 1 (mIDH1) gene in patients (pts) with cholangiocarcinoma (CCA) in the phase III ClarIDHy study. To further consolidate safety and efficacy data of IVO in the real world, the ProvIDHe study was initiated.

Methods

This is an international, single-arm phase IIIb, enabling pts with CCA access to IVO treatment. Adult pts with locally advanced or metastatic mIDH1 CCA who had received at least one prior line of systemic treatment are eligible. Pts receive 500 mg IVO orally once daily and continue treatment as long as clinical benefit is observed, until unacceptable toxicity, or until IVO is accessible via medical prescription. The primary endpoint of the study is safety. Baseline characteristics and molecular testing outcomes are presented here.

Results

On 9 July, 206 pts from 12 countries were enrolled. Hereafter, we present the analysis as of the cut-off date of 9 February 2024: 158 pts from 10 countries were enrolled. 131 pts were included in the safety analysis set (Table). Most pts were <75 years old (84.2%), had stage IV disease (89.2%), and had liver metastases (72.8%) at screening. The main molecular testing method used was next-generation sequencing (77.1%) with a median turnaround time of 13 days. 67.9% of pts had mIDH1 R132C. The most frequent co-alterations recorded were PIK3CA (9.9%), FGFR2 (4.6%) and BRAF V600E (3.9%). The median number of prior systemic regimens for advanced/metastatic disease was 2 (range, 1-6), most commonly gemcitabine + cisplatin alone (39.7%) or with immunotherapy (35.1%) Table: 138MO

Baseline characteristics

CCA, Cholangiocarcinoma; ECOG PS, eastern cooperative oncology group performance status. *n=131, as per current analysis, 25 pts did not receive prior therapy for advanced/metastatic disease

Conclusions

This first interim analysis focused on baseline characteristics of pts enrolled in the ProvIDHe study, including previous treatment regimens for advanced/metastatic disease and molecular testing. The study is still enrolling, and future analyses will focus on patient outcomes.

Clinical trial identification

NCT05876754.

Editorial acknowledgement

Legal entity responsible for the study

Servier Affaires Médicales.

Funding

Servier.

Disclosure

L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AbbVie, AstraZeneca, Basilea, Bayer, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Guerbet, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Zymeworks, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche, Servier; Financial Interests, Institutional, Coordinating PI, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Local PI: Agios, Eisai, Fibrogen, Lilly, MSD, Roche, Servier; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Coordinating PI, European PI: AstraZeneca, TransThera Sciences, Taiho Oncology; Non-Financial Interests, Personal, Leadership Role, Treasurer: ILCA; Non-Financial Interests, Personal, Leadership Role, Chair: EORTC GITCG HPB/NET Task Force; Non-Financial Interests, Personal, Other, Special Expert Clinical Trials Europe: NCI HB Task Force. J.A. Bridgewater: Financial Interests, Personal, Advisory Board: Taiho, BMS, Incyte, Basilea, Servier; Financial Interests, Personal, Other, Advisor: AstraZeneca; Financial Interests, Institutional, Funding: Incyte. A. Casadei-Gardini: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bayer, BMS, Eisai, Incyte, Ipsen, IQVIA, MSD, Roche, Servier; Financial Interests, Personal, Other, Travel: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Eisai. H. Wilmink: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, MSD; Financial Interests, Personal, Speaker’s Bureau: MSD, Servier; Financial Interests, Personal, Research Funding: MSD, Nordic Group, Servier. H. Sim: Financial Interests, Personal, Other, Honoraria: Eli Lilly, Servier; Financial Interests, Institutional, Research Grant: AbbVie, Bristol Myers Squibb. J. de vos-Geelen: Financial Interests, Institutional, Research Grant: Servier. T. Macarulla Mercade: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd, Celgene SLU, Eisai, Ipsen Pharma, Incyte; Financial Interests, Personal, Other, Direct research fund: Servier, Merck Sharp & Dohme, Novocure, QED Therapeutics Inc, Roche, Sanofi-Aventis, Zymeworks; Financial Interests, Personal, Invited Speaker: Lilly, Janssen; Financial Interests, Institutional, Research Grant: Amc Medical Research, Armo Biosciences, Basilea, Biokeralty Research Institute, Merck Sharp & Dohme, Oncomed Pharmaceuticals, QED Therapeutics, VCN Biosciences, AbbVie Farmaceútica, Ability Pharmaceuticals, Agios, Amgen, Aslan, AstraZeneca, Bayer, Beigene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, Fibrogen, Genentech, Hallozyme, Immunomedics, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, Medimmune, Merimarck, Millenim, Nelum, Novartis, Novocure, Pfizer, Pharmacyclics, Roche, Zymeworks; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO; Other, Personal, Other, Editorial Board: GI Annals og¡f Oncology. D. Malka: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Incyte, Merck Serono, MSD, Pierre Fabre Oncologie, Roche, Sanofi, Servier, Taiho, Viatris; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, BMS, Foundation Medicine, Incyte, Leo Pharma, Medscape, Merck Serono, MSD, Pierre Fabre Oncologie, Roche, Sanofi, Servier, Veracyte, Viatris; Financial Interests, Personal, Other, Travel: Amgen, Bayer, BMS, Merck Serono, MSD, Pierre Fabre Oncology, Roche, Sanofi, Servier, Viatris. H. Gharbi, R. Robert, A. Sullivan: Financial Interests, Personal, Full or part-time Employment: Servier. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Mannheim, Eisai, Incyte, Ipsen, MSD, Roche, Servier, Tyra, Taiho, AbbVie; Financial Interests, Personal, Invited Speaker: BMS, EISAI, IPSEN, MSD, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Roche, MSD, Beigene, Boehringer-Ingelheim.