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

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

NCT ID: NCT05921760

Condition: IDH1-mutant Cholangiocarcinoma

Conditions: Official terms:
Cholangiocarcinoma
Nivolumab
Ipilimumab
Ivosidenib
Glycine

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Active, not recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Ivosidenib
Description: ivosidenib taken once daily
Arm group label: Safety Lead-In Phase - ivosidenib

Intervention type: Drug
Intervention name: Recommended Combination Dose (RCD) of ivosidenib
Description: The RCD of ivosidenib taken once daily
Arm group label: Experimental Phase - Cohort 1
Arm group label: Experimental Phase - Cohort 2

Intervention type: Drug
Intervention name: Nivolumab
Description: Nivolumab taken by intravenous infusion
Arm group label: Experimental Phase - Cohort 1
Arm group label: Experimental Phase - Cohort 2
Arm group label: Safety Lead-In Phase - ivosidenib

Intervention type: Drug
Intervention name: Ipilimumab
Description: Ipilimumab taken by intravenous infusion
Arm group label: Experimental Phase - Cohort 1
Arm group label: Experimental Phase - Cohort 2
Arm group label: Safety Lead-In Phase - ivosidenib

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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. Exclusion Criteria: - 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: UCSF - Medical Center at Mission Bay

Address:
City: San Francisco
Zip: 94158
Country: United States

Facility:
Name: Ucsf Helen Diller Family Comprehensive Cancer Center

Address:
City: San Francisco
Zip: 94158
Country: United States

Facility:
Name: Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins

Address:
City: Baltimore
Zip: 21231
Country: United States

Facility:
Name: Dana Farber Cancer Institute

Address:
City: Boston
Zip: 02215
Country: United States

Facility:
Name: UCLH

Address:
City: London
Zip: NW1 2PG
Country: United Kingdom

Start date: October 23, 2023

Completion date: March 2026

Lead sponsor:
Agency: Servier Bio-Innovation LLC
Agency class: Industry

Collaborator:
Agency: Institut de Recherches Internationales Servier
Agency class: Other

Source: Servier

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05921760