IDH1-mutant CholangiocarcinomaPhase 1/2NCT05921760
Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma
A Phase 1/2 study testing Ivosidenib, Nivolumab and Ipilimumab in people with IDH1-mutant Cholangiocarcinoma, run by Servier Bio-Innovation LLC at 5 sites in 2 countries.
Trial summary
This is a Phase 1/2 study evaluating the safety, tolerability, and activity of ivosidenib in combination with immunotherapy in participants with nonresectable or metastatic cholangiocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- IDH1-mutant Cholangiocarcinoma
- What is being tested?
- Ivosidenib, Nivolumab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 23 Oct 2023to 21 Nov 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male of female participant age ≥ 18 years old
- Have documented IDH1 gene-mutated disease based on local testing procedure (R132C/L/G/H/S mutations variants tested)
- Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
- Has a histopathological diagnosis consistent with nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies
- Participants must have at least one measurable lesion as defined by RECIST Version 1.1. Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or if within the field but has shown ≥ 20% growth in size post-treatment assessment.
Who cannot join
- Received prior treatment with an IDH inhibitor or prior treatment with an immune checkpoint inhibitor other than anti-PD1/L1
- Have active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment
- Participants who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 1 non-hematologic toxicity, according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, prior to the first IMP administration. Residual Grade ≤ 2 toxicity from chemotherapy (e.g., alopecia, neuropathy) may be allowed.
- Have known symptomatic brain metastases requiring steroids. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and have radiographically stable disease for at least 3 months prior to study entry. Note: Up to 10 mg per day of prednisone equivalent will be allowed.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
Baltimore, Maryland, 21231
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
UCSF - Medical Center at Mission Bay
San Francisco, California, 94158
Ucsf Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
About this study
Official title: A Phase 1/2, Safety Lead-in and Dose Expansion, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Nivolumab and Ipilimumab in Previously Treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
This is a Phase 1/2 study evaluating the safety, tolerability, and activity of ivosidenib in combination with immunotherapy in participants with nonresectable or metastatic cholangiocarcinoma. The study includes two phases: the safety lead-in phase to determine the recommended combination dose (RCD) of ivosidenib in combination with immunotherapy and the dose expansion phase to assess the efficacy of ivosidenib in combination with immunotherapy. Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met.
This study was terminated by the sponsor before the expansion phase began and therefore participants were only involved in the safety lead-in phase.
- Conditions
- IDH1-mutant Cholangiocarcinoma
- Being tested
- Ivosidenib, Nivolumab, Ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvosidenibDrug
ivosidenib taken once daily
NivolumabDrug
Nivolumab taken by intravenous infusion
IpilimumabDrug
Ipilimumab taken by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Safety Lead-In Phase - Ivosidenib 500mg | Experimental | Not described Receives: Drug: Ivosidenib; Drug: Nivolumab; Drug: Ipilimumab |
| Safety Lead-In Phase - Ivosidenib 250mg | Experimental | Not described Receives: Drug: Ivosidenib; Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Lead-In Phase: Number of Dose Limiting Toxicities (DLTs) Associated With Study Drug Regimen, During the First 2 Cycles of Treatment
Occurring during the safety lead-in phase
Measured: Through the end of Cycle 2, day 42 (Cycle 1 and 2 are each 21 days)
Safety Lead-In Phase: Number of Adverse Events (AEs)
Occurring during the safety lead-in phase
Measured: Through study termination (approximately 1 year)
Safety Lead-In Phase: Number of Participants With Adverse Events of Special Interests (AESIs)
Occurring during the safety lead-in phase
Measured: Through study termination (approximately 1 year)
Safety Lead-In Phase: Number of Serious Adverse Events (SAEs)
Occurring during the safety lead-in phase
Measured: Through study termination (approximately 1 year)
Secondary outcomes (8)
Safety Lead-In Phase: Area Under the Concentration-vs-time Curve (AUC) From 0 to Time of Last Measurable Concentration (AUC0-t)
Occurring during the safety lead-in phase
Measured: Up to 3 years
Safety Lead-In Phase: Plasma 2-hydroxyglutarate (2-HG) Concentration
Occurring during the safety lead-in phase
Measured: up to 3 years
Safety Lead-In Phase: AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)
Occurring during the safety lead-in phase
Measured: Up to 3 years
Safety Lead-In Phase: Time to Maximum Concentration (Tmax)
Occurring during the safety lead-in phase
Measured: Up to 3 years
Safety Lead-In Phase: Maximum Concentration (Cmax)
Occurring during the safety lead-in phase
Measured: Up to 3 years
Safety Lead-In Phase: Trough Concentration (Ctrough)
Occurring during the safety lead-in phase
Measured: Up to 3 years
Safety Lead-In Phase: Apparent Volume of Distribution (Vd/F)
Occurring during the safety lead-in phase
Measured: Up to 3 years
Safety Lead-In Phase: Apparent Clearance (CL/F)
Occurring during the safety lead-in phase
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2023
- Study start23 Oct 2023
- Primary completion21 Nov 2024
- Study completion21 Nov 2024
Why it stopped: The sponsor decided to terminate the study during the safety lead-in phase.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IDH1-mutant CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Servier Bio-Innovation LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Institut de Recherches Internationales Servier
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05921760
- Sponsor's protocol ID
- CL1-95031-006
- Status last verified
- Mar 2026
- First submitted
- 21 Apr 2023
- Last updated
- 20 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Kelley RK, Cleary JM, Sahai V, Baretti M, Bridgewater JA, Hua Z, Gliser C, Bian Y, Abou-Alfa GK. A phase 1/2, safety lead-in and dose expansion, open-label, multicenter trial investigating the safety, tolerability, and preliminary activity of ivosidenib in combination with nivolumab and ipilimumab in previously treated subjects with IDH1-mutated nonresectable or metastatic cholangiocarcinoma. J Clin Oncol. 2024 May 29;42(16_Supplement):TPS4197. doi: https://doi.org/10.1200/JCO.2024.42.16_suppl.TPS4197
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Safety Lead-in and Dose Expansion, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Nivolumab and Ipilimumab in Previously Treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
- ClinicalTrials.gov ID
- NCT05921760
- Acronym / sponsor ID
- CL1-95031-006
- Conditions
- IDH1-mutant Cholangiocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided to terminate the study during the safety lead-in phase.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Servier Bio-Innovation LLCIndustry (pharma, biotech, devices)
- Collaborators
- Institut de Recherches Internationales Servier
- Study start
- 23 Oct 2023 (actual)
- Primary completion
- 21 Nov 2024 (actual)
- Study completion
- 21 Nov 2024 (actual)
- First posted
- 27 Jun 2023 (actual)
- Results
- Posted 12 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2 study evaluating the safety, tolerability, and activity of ivosidenib in combination with immunotherapy in participants with nonresectable or metastatic cholangiocarcinoma. The study includes two phases: the safety lead-in phase to determine the recommended combination dose (RCD) of ivosidenib in combination with immunotherapy and the dose expansion phase to assess the efficacy of ivosidenib in combination with immunotherapy. Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met.
This study was terminated by the sponsor before the expansion phase began and therefore participants were only involved in the safety lead-in phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Safety Lead-In Phase - Ivosidenib 500mg | Experimental | Drug: Ivosidenib, Drug: Nivolumab, Drug: Ipilimumab |
| Safety Lead-In Phase - Ivosidenib 250mg | Experimental | Drug: Ivosidenib, Drug: Nivolumab, Drug: Ipilimumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male of female participant age ≥ 18 years old
- Have documented IDH1 gene-mutated disease based on local testing procedure (R132C/L/G/H/S mutations variants tested)
- Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
- Has a histopathological diagnosis consistent with nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies
- Participants must have at least one measurable lesion as defined by RECIST Version 1.1. Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or if within the field but has shown ≥ 20% growth in size post-treatment assessment.
Key exclusion criteria (4 listed)
- Received prior treatment with an IDH inhibitor or prior treatment with an immune checkpoint inhibitor other than anti-PD1/L1
- Have active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment
- Participants who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 1 non-hematologic toxicity, according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, prior to the first IMP administration. Residual Grade ≤ 2 toxicity from chemotherapy (e.g., alopecia, neuropathy) may be allowed.
- Have known symptomatic brain metastases requiring steroids. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and have radiographically stable disease for at least 3 months prior to study entry. Note: Up to 10 mg per day of prednisone equivalent will be allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivosidenibivosidenib taken once daily | Drug | Safety Lead-In Phase - Ivosidenib 250mg, Safety Lead-In Phase - Ivosidenib 500mg |
| NivolumabNivolumab taken by intravenous infusion | Drug | Safety Lead-In Phase - Ivosidenib 250mg, Safety Lead-In Phase - Ivosidenib 500mg |
| IpilimumabIpilimumab taken by intravenous infusion | Drug | Safety Lead-In Phase - Ivosidenib 250mg, Safety Lead-In Phase - Ivosidenib 500mg |
Primary outcome
Safety Lead-In Phase: Number of Dose Limiting Toxicities (DLTs) Associated With Study Drug Regimen, During the First 2 Cycles of Treatment
Time frame: Through the end of Cycle 2, day 42 (Cycle 1 and 2 are each 21 days)
Occurring during the safety lead-in phase
Safety Lead-In Phase: Number of Adverse Events (AEs)
Time frame: Through study termination (approximately 1 year)
Occurring during the safety lead-in phase
Safety Lead-In Phase: Number of Participants With Adverse Events of Special Interests (AESIs)
Time frame: Through study termination (approximately 1 year)
Occurring during the safety lead-in phase
Safety Lead-In Phase: Number of Serious Adverse Events (SAEs)
Time frame: Through study termination (approximately 1 year)
Occurring during the safety lead-in phase
8 secondary outcomes
Safety Lead-In Phase: Area Under the Concentration-vs-time Curve (AUC) From 0 to Time of Last Measurable Concentration (AUC0-t)
Time frame: Up to 3 years
Safety Lead-In Phase: Plasma 2-hydroxyglutarate (2-HG) Concentration
Time frame: up to 3 years
Safety Lead-In Phase: AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)
Time frame: Up to 3 years
Safety Lead-In Phase: Time to Maximum Concentration (Tmax)
Time frame: Up to 3 years
Safety Lead-In Phase: Maximum Concentration (Cmax)
Time frame: Up to 3 years
Safety Lead-In Phase: Trough Concentration (Ctrough)
Time frame: Up to 3 years
Safety Lead-In Phase: Apparent Volume of Distribution (Vd/F)
Time frame: Up to 3 years
Safety Lead-In Phase: Apparent Clearance (CL/F)
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundKelley RK, Cleary JM, Sahai V, Baretti M, Bridgewater JA, Hua Z, Gliser C, Bian Y, Abou-Alfa GK. A phase 1/2, safety lead-in and dose expansion, open-label, multicenter trial investigating the safety, tolerability, and preliminary activity of ivosidenib in combination with nivolumab and ipilimumab in previously treated subjects with IDH1-mutated nonresectable or metastatic cholangiocarcinoma. J Clin Oncol. 2024 May 29;42(16_Supplement):TPS4197. doi: https://doi.org/10.1200/JCO.2024.42.16_suppl.TPS4197
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ivosidenib, Nivolumab and Ipilimumab in people with IDH1-mutant Cholangiocarcinoma, run by Servier Bio-Innovation LLC at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Lead-In Phase: Number of Dose Limiting Toxicities (DLTs) Associated With Study Drug Regimen, During the First 2 Cycles of Treatment (time frame: Through the end of Cycle 2, day 42 (Cycle 1 and 2 are each 21 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05921760, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2026.