Trial Outcomes & Findings for A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation (NCT NCT06081829)

NCT ID: NCT06081829

Last Updated: 2025-12-09

Results Overview

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)

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: Through 6 months after the first dose
• Results posted on: 2025-12-09

Participant Flow

Participant milestones

Measure	Open-Label Ivosidenib 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Overall Study STARTED	12
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Measure	Open-Label Ivosidenib 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Overall Study Participants still on-study	8
Overall Study Death	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Age, Continuous	61.5 years STANDARD_DEVIATION 12.27 • n=4 Participants
Age, Customized 45-<65 years old	7 Participants n=4 Participants
Age, Customized >=65 years old	5 Participants n=4 Participants
Sex: Female, Male Female	5 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	12 Participants n=4 Participants
Race/Ethnicity, Customized Asian	12 Participants n=4 Participants
Body Mass Index (BMI)	23.1 kg/m^2 STANDARD_DEVIATION 4.39 • n=4 Participants

PRIMARY outcome

Timeframe: Through 6 months after the first dose

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)

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
6-month Progression Free Survival (PFS) Rate	25.0 percentage of participants Interval 8.1 to 46.5

SECONDARY outcome

Timeframe: Approximately 1 year

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

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Progression Free Survival (PFS)	4.21 months Interval 2.69 to Data was not estimable (survival time exceeds the longest observed or censored survival time as of the data cut-off date)

SECONDARY outcome

Timeframe: Approximately 1 year

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Overall Survival (OS)	NA months Interval 5.19 to Data was not estimable (median survival time exceeds the longest observed or censored survival time as of the data cut-off date)

SECONDARY outcome

Timeframe: Approximately 1 year

Complete response or partial response

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Objective Response (OR) Rate	0 Participants

SECONDARY outcome

Timeframe: Approximately 1 year

Population: No participants achieved a complete response or partial response, and therefore there were no participants who could be assessed for their duration of response.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 1 year

Population: No participants achieved a complete response or partial response, and therefore there were no participants who could be assessed for their time to response.

The time from Day 1 to date of first documented confirmed complete response (CR) or confirmed partial response (PR)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 1 year

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.

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Outcome measures

Measure	Open-Label Ivosidenib n=9 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Physical Functioning	-6.7 score on a scale Standard Deviation 15.63
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Role Functioning	-9.3 score on a scale Standard Deviation 16.90
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Cognitive Functioning	-1.9 score on a scale Standard Deviation 10.02
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Emotional Functioning	-8.3 score on a scale Standard Deviation 18.63
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Social Functioning	-14.8 score on a scale Standard Deviation 17.57
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Fatigue	7.4 score on a scale Standard Deviation 16.67
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Pain	7.4 score on a scale Standard Deviation 32.39
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Nausea/Vomiting	7.4 score on a scale Standard Deviation 12.11
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Dyspnea	22.2 score on a scale Standard Deviation 40.82
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Insomnia	18.5 score on a scale Standard Deviation 29.40
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Appetite Loss	7.4 score on a scale Standard Deviation 32.39
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Constipation	-7.4 score on a scale Standard Deviation 14.70
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Diarrhea	3.7 score on a scale Standard Deviation 20.03
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. Financial Difficulties	0.0 score on a scale Standard Deviation 23.57
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores. GHS	-20.4 score on a scale Standard Deviation 22.48

SECONDARY outcome

Timeframe: Baseline and 1 year

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.

Outcome measures

Measure	Open-Label Ivosidenib n=9 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-BIL21 Questionnaire Scores.	8.3 score on a scale Standard Deviation 12.50

SECONDARY outcome

Timeframe: 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)

Population: The number analyzed differs due to missing participant data.

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.

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Average EQ-5D-5L VAS Scores End of Treatment	61.7 score on a scale Standard Deviation 27.05
Average EQ-5D-5L VAS Scores Baseline	78.8 score on a scale Standard Deviation 10.80
Average EQ-5D-5L VAS Scores Cycle 3 Day 1	75.8 score on a scale Standard Deviation 15.61

SECONDARY outcome

Timeframe: Approximately 1 year

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Total Number of Adverse Events (AEs)	24 Number of Adverse Events

SECONDARY outcome

Timeframe: Approximately 1 year

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Total Number of Participants With Adverse Events (AEs) Leading to Dose Modifications	0 Participants

SECONDARY outcome

Timeframe: Approximately 1 year

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Total Number of Participants With Adverse Events (AEs) Leading to Discontinuation	0 Participants

SECONDARY outcome

Timeframe: Approximately 1 year

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Total Number of Participants With Serious Adverse Events (SAEs)	2 Participants

SECONDARY outcome

Timeframe: Approximately 1 year

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Total Number of Participants With Adverse Events (AEs) Leading to Death	0 Participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant was excluded from Cycle 2 Day 1 data analysis since their dose was reduced.

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Average Area Under the Concentration-vs Time Curve From 0 to Time of Last Measurable Concentration (AUC0-t) Cycle 1 Day 1	18699 ng*h/mL Geometric Coefficient of Variation 43.5
Average Area Under the Concentration-vs Time Curve From 0 to Time of Last Measurable Concentration (AUC0-t) Cycle 2 Day 1	22404 ng*h/mL Geometric Coefficient of Variation 27.4

SECONDARY outcome

Timeframe: Cycle 2 Day 1

Outcome measures

Measure	Open-Label Ivosidenib n=11 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Average AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)	74121 ng*h/mL Geometric Coefficient of Variation 30.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant's data was excluded from Cycle 2 Day 1 since the ivosidenib dose was reduced.

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Average Time to Maximum Concentration (Tmax) Cycle 1 Day 1	2.98 hours Interval 1.85 to 5.93
Average Time to Maximum Concentration (Tmax) Cycle 2 Day 1	3.83 hours Interval 1.83 to 3.97

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant's data was excluded from Cycle 2 Day 1 since the ivosidenib dose was reduced.

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Average Maximum Concentration (Cmax) Cycle 1 Day 1	4918 ng/mL Geometric Coefficient of Variation 42.7
Average Maximum Concentration (Cmax) Cycle 2 Day 1	4781 ng/mL Geometric Coefficient of Variation 22.8

SECONDARY outcome

Timeframe: Cycle 2 Day 1

Outcome measures

Measure	Open-Label Ivosidenib n=11 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Average Trough Concentration (Ctrough)	2058 ng/mL Geometric Coefficient of Variation 28.7

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant's data was excluded from Cycle 2 Day 1 since the ivosidenib dose was reduced.

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Average Plasma 2-hydroxyglutarate (2-HG) Concentrations Cycle 1 Day 1	597 ng/mL Standard Deviation 532.07
Average Plasma 2-hydroxyglutarate (2-HG) Concentrations Cycle 2 Day 1	79.95 ng/mL Standard Deviation 41.166

SECONDARY outcome

Timeframe: Approximately 1 year

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.

Outcome measures

Measure	Open-Label Ivosidenib n=12 Participants 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
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 Baseline Score of 1 and Worst Post-Baseline Score of 1 (no change)	2 Participants
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 Baseline Score of 0 and Worst Post-Baseline Score of 0 (no change)	7 Participants
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 Baseline Score of 0 and Worst Post-Baseline Score of 1 (+1 change)	2 Participants
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 Baseline Score of 0 and Worst Post-Baseline Score of 2 (+2 change)	1 Participants

Adverse Events

Open-Label Ivosidenib

Serious events: 2 serious events

Other events: 9 other events

Deaths: 4 deaths

Serious adverse events

Measure	Open-Label Ivosidenib n=12 participants at risk 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Investigations Electrocardiogram QT prolonged	16.7% 2/12 • Approximately 1 year Adverse events will be assessed during study visits.

Other adverse events

Measure	Open-Label Ivosidenib n=12 participants at risk 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.
Gastrointestinal disorders Diarrhea	16.7% 2/12 • Approximately 1 year Adverse events will be assessed during study visits.
Gastrointestinal disorders Dry mouth	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Gastrointestinal disorders Dyspepsia	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Gastrointestinal disorders Nausea	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Gastrointestinal disorders Stomatitis	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Gastrointestinal disorders Vomiting	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
General disorders Fatigue	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
General disorders Malaise	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
General disorders Pyrexia	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Infections and infestations COVID-19	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Investigations Electrocardiogram QT prolonged	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Investigations Lymphocyte count decreased	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Investigations Weight decreased	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Metabolism and nutrition disorders Hypokalaemia	16.7% 2/12 • Approximately 1 year Adverse events will be assessed during study visits.
Metabolism and nutrition disorders Decreased appetite	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Metabolism and nutrition disorders Hyperuricaemia	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Musculoskeletal and connective tissue disorders Back pain	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Musculoskeletal and connective tissue disorders Neck pain	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Skin and subcutaneous tissue disorders Rash	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.
Skin and subcutaneous tissue disorders Urticaria	8.3% 1/12 • Approximately 1 year Adverse events will be assessed during study visits.

Additional Information

Clinical Studies Department

Institut de Recherches Internationales Servier (I.R.I.S.)

Phone: +33 1 55 72 60 00

Email: scientificinformation@servier.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place