A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

A Phase 2, Open-label, Multicenter Study of Orally Administered Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

This study will enroll participants with nonresectable or metastatic cholangiocarcinoma with an Isocitrate dehydrogenase protein, 1 (IDH1) mutation, who have previously received at least 1, but no more than 2, prior regimens for advanced disease. All participants will receive ivosidenib daily throughout multiple 28 day cycles. Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met. Study visits will be conducted every week during Cycle 1 (Days 1, 8, 15, and 22), every other week during Cycles 2 and 3, and Day 1 of each cycle thereafter. After the last dose of treatment, participants will attend an end of treatment and a post-treatment follow-up visit, and participants will be followed to assess overall survival. Study visits may include a tumor assessment, physical exam, electrocardiogram (ECG), blood and urine analysis, and questionnaires.

Study Overview

• Status: Active, not recruiting
• Conditions: Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic
• Intervention / Treatment: Drug: Ivosidenib

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East (JPN-002)
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital (JPN-004)
  • Matsuyama, Japan, 791-0280
    • National Hospital Organization Shikoku Cancer Center (JPN-007)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute (JPN-005)
  • Sapporo, Japan, 060-8648
    • Hokkaido University Hospital (JPN-006)
  • Tokyo, Japan
    • National Cancer Center Hospital (JPN-001)
  • Yokohama, Japan, 241-8515
    • Kanagawa Cancer Center (JPN-003)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation or ablative therapies
• Have documented IDH1 gene-mutated disease from a tumor biopsy
• Have an ECOG PS score of 0 or 1
• Have an expected survival of 3 months or more
• Have at least one evaluable and measurable lesion
• Have disease progression following the most recent of 1 or 2 prior systemic regimens for advanced disease with progression on the treatment that was most recently given at a minimum, and must have received at least 1 gemcitabine- or 5-FU -containing regimen
• Have recovered from side effects associated with the prior treatment therapy
• Have adequate bone marrow function
• Have adequate hepatic (liver) and renal (kidney) function
• Women of child bearing potential must have a negative serum pregnancy test before starting study treatment, and use birth control during the study and for 90 days after the last dose of ivosidenib
• Fertile men with female partners of child bearing potential must use birth control during the study and for 90 days after the last dose of ivosidenib

Exclusion Criteria:

• Received a prior IDH inhibitor.
• Have known symptomatic brain metastases requiring steroids.
• Pregnancy, possibility of becoming pregnant during the study and breast-feeding women or woman who plans to restart breast-feeding after the study drug administration/intake.
• Are taking known strong cytochrome P450 (CYP) 3A4 inducers or sensitive CYP3A4 substrate medications with a narrow therapeutic window
• Have significant heart disease, including congestive heart failure, myocardial infarction (heart attack) unstable angina (chest pain) and/or stroke, within 6 months before starting the study
• Have a heart-rate corrected QT interval ≥450 msec or other factors that increase the risk of QT prolongation or arrhythmic events
• . Have active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis (paralysis of the stomach), or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
• Have known medical history of progressive multifocal leukoencephalopathy (PML)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label Ivosidenib; 250 mg Tablets	Drug: Ivosidenib; Subjects will take 2 tablets (500 mg total) orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month Progression Free Survival (PFS) Rate	Proportion of subjects who are alive and progression-free (using RECIST v1.1) at 6 months after Day 1 (C1D1) per Independent Radiology Center (IRC)	Through 6 months after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	The time from Day 1 to the date of first documentation of disease progression as assessed by the Investigator and by the IRC per RECIST v1.1. or death due to any cause	Approximately 1 year
Overall Survival (OS)		Approximately 1 year
Objective Response (OR) Rate	Complete response or partial response	Approximately 1 year
Duration of Response (DOR)	The time from date of first documented confirmed complete response (CR) or confirmed partial response (PR) to date of first documented disease progression or death due to any cause	Approximately 1 year
Time to Response (TTR)	The time from Day 1 to date of first documented confirmed complete response (CR) or confirmed partial response (PR)	Approximately 1 year
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30) is comprised of 5 functional scales ((Physical functioning, Role functioning, Cognitive functioning, Emotional functioning and Social functioning), 3 symptom scales (Fatigue, Pain and Nausea/Vomiting), 6 additional single items (Dyspnoea, Insomnia, Appetite Loss, Constipation, Diarrhoea and Financial Difficulties) and global health status (GHS). All of the scale scores range from 0 - 100; for the functional scales and GHS the higher score represents better functioning and for the symptom scales and single items the higher score represents an increase in symptoms. .	Baseline and 1 year
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-BIL21 Questionnaire Scores.	The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (EORTC-QLQ-BIL21) scores range from 0 - 100 with higher scores representing more severe symptoms.	Baseline and 1 year
Average EQ-5D-5L VAS Scores	The 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) visual analogue scale (VAS) scores range from 0 to 100 with a higher number representing a better health status.	Baseline, Cycle 3 Day 1 (cycle = 28 days), and End of Treatment Visit (within 5 to 33 days after last dose of treatment, approximately 1 year total)
Total Number of Adverse Events (AEs)		Approximately 1 year
Total Number of Participants With Adverse Events (AEs) Leading to Dose Modifications		Approximately 1 year
Total Number of Participants With Adverse Events (AEs) Leading to Discontinuation		Approximately 1 year
Total Number of Participants With Serious Adverse Events (SAEs)		Approximately 1 year
Total Number of Participants With Adverse Events (AEs) Leading to Death		Approximately 1 year
Average Area Under the Concentration-vs Time Curve From 0 to Time of Last Measurable Concentration (AUC0-t)		Cycle 1 Day 1 and Cycle 2 Day 1
Average AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)		Cycle 2 Day 1
Average Time to Maximum Concentration (Tmax)		Cycle 1 Day 1 and Cycle 2 Day 1
Average Maximum Concentration (Cmax)		Cycle 1 Day 1 and Cycle 2 Day 1
Average Trough Concentration (Ctrough)		Cycle 2 Day 1
Average Plasma 2-hydroxyglutarate (2-HG) Concentrations		Cycle 1 Day 1 and Cycle 2 Day 1
Number of Participants With no Change, Plus 1 or Plus 2 Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG PS) Score	From baseline to worst value of post-baseline assessments. ECOG PS scores range from 0 to 5 with 0 representing a person being fully active and 5 being the patient is dead.	Approximately 1 year

Collaborators and Investigators

• Sponsor: Servier

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Actual): October 1, 2024
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 14, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: IDH-1 Mutation; Cholangiocarcinoma Non-resectable with an IDH-1 Mutation; Cholangiocarcinoma Metastatic with an IDH-1 Mutation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; ivosidenib
• Other Study ID Numbers: CL2-95031-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes