Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma

NCT05921760 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: CL1-95031-006
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 5

Brief 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. 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

Outcome Measures

Primary Outcomes (4)

• 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

  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

  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

  Through study termination (approximately 1 year)

• Safety Lead-In Phase: Number of Serious Adverse Events (SAEs)

  Occurring during the safety lead-in phase

  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)

  Up to 3 years

• Safety Lead-In Phase: Plasma 2-hydroxyglutarate (2-HG) Concentration

  up to 3 years

• Safety Lead-In Phase: AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)

  Up to 3 years

• Safety Lead-In Phase: Time to Maximum Concentration (Tmax)

  Up to 3 years

• Safety Lead-In Phase: Maximum Concentration (Cmax)

  Up to 3 years

Study Arms (2)

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

Interventions

Ivosidenib DRUG

ivosidenib taken once daily

Safety Lead-In Phase - Ivosidenib 250mg; Safety Lead-In Phase - Ivosidenib 500mg

Nivolumab DRUG

Nivolumab taken by intravenous infusion

Safety Lead-In Phase - Ivosidenib 250mg; Safety Lead-In Phase - Ivosidenib 500mg

Ipilimumab DRUG

Ipilimumab taken by intravenous infusion

Safety Lead-In Phase - Ivosidenib 250mg; Safety Lead-In Phase - Ivosidenib 500mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Servier Bio-Innovation LLC: lead
• Institut de Recherches Internationales Servier: collaborator

Study Sites (5)

UCSF - Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

Ucsf Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

UCLH

London, NW1 2PG, United Kingdom

Location

Related Publications (1)

• 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

  BACKGROUND

MeSH Terms

Interventions

ivosidenib; Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Institut de Recherches Internationales Servier (I.R.I.S.)
• Organization: Clinical Studies Department

scientificinformation@servier.com

+33 1 55 72 60 00

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2023
• First Posted: June 27, 2023
• Study Start: October 23, 2023
• Primary Completion: November 21, 2024
• Study Completion: November 21, 2024
• Last Updated: April 20, 2026
• Results First Posted: February 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• 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.

Locations

US (4); GB (1)