Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma
- Conditions
- IDH1-mutant Cholangiocarcinoma
- Interventions
- Drug: Recommended Combination Dose (RCD) of ivosidenib
- Registration Number
- NCT05921760
- Lead Sponsor
- Servier Bio-Innovation LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Phase - Cohort 1 Nivolumab Second phase of the study. Cohort 1 will include the anti-PD1/L1-naïve subpopulation. Experimental Phase - Cohort 1 Ipilimumab Second phase of the study. Cohort 1 will include the anti-PD1/L1-naïve subpopulation. Experimental Phase - Cohort 2 Recommended Combination Dose (RCD) of ivosidenib Second phase of the study. Cohort 2 will include the anti-PD1/L1 previously treated subpopulation. Safety Lead-In Phase - ivosidenib Ivosidenib First phase of the study. Safety Lead-In Phase - ivosidenib Nivolumab First phase of the study. Experimental Phase - Cohort 1 Recommended Combination Dose (RCD) of ivosidenib Second phase of the study. Cohort 1 will include the anti-PD1/L1-naïve subpopulation. Experimental Phase - Cohort 2 Nivolumab Second phase of the study. Cohort 2 will include the anti-PD1/L1 previously treated subpopulation. Experimental Phase - Cohort 2 Ipilimumab Second phase of the study. Cohort 2 will include the anti-PD1/L1 previously treated subpopulation. Safety Lead-In Phase - ivosidenib Ipilimumab First phase of the study.
- Primary Outcome Measures
Name Time Method Safety Phase: To determine the recommended combination dose (RDC) of ivosidenib in combination of immunotherapy Through the end of Cycle 2, day 42 (Cycle 1 and 2 are each 21 days) Occurring during the safety lead-in phase
Safety Phase: Number of Adverse Events of Special Interests (AESIs) Up to 3 years Occurring during the safety lead-in phase
Expansion Phase: To assess the Objective Response (confirmed complete response [CR] or confirmed partial response [PR]) of antitumor activity using RECIST v1.1) up to 3 years To assess the Objective Response (confirmed complete response \[CR\] or confirmed partial response \[PR\]) of antitumor activity using RECIST v1.1)
Safety Phase: Number of Adverse Events (AEs) Up to 3 years Occurring during the safety lead-in phase
Safety Phase: Number of Serious Adverse Events (SAEs) Up to 3 years Occurring during the safety lead-in phase
Safety Phase: Number of dose limiting toxicities (DLTs) associated with study drug regimen, during the first 2 cycles of treatment Through the end of Cycle 2, day 42 (Cycle 1 and 2 are each 21 days) Occurring during the safety lead-in phase
- Secondary Outcome Measures
Name Time Method Expansion Phase: time to maximum concentration (Tmax) Up to 3 years Occurring during the expansion phase
Safety Phase: area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t) Up to 3 years Occurring during the safety lead-in phase
Expansion Phase: progression-free survival (PFS) up to 3 years Occurring during the expansion phase
Expansion Phase: time to response (TTR) according to RECIST v1.1 up to 3 years Occurring during the expansion phase
Expansion Phase: Duration of response (DOR) up to 3 years Occurring during the expansion phase
Expansion Phase: Overall survival (OS) up to 3 years Occurring during the expansion phase
Safety Phase: apparent clearance (CL/F) Up to 3 years Occurring during the safety lead-in phase
Expansion Phase: Number of Serious Adverse Events (SAEs) Up to 3 years Occurring during the expansion phase
Expansion Phase: Number of Adverse Events (AEs) Up to 3 years Occurring during the expansion phase
Expansion Phase: disease control (DC) (complete response-CR, partial response-PR, or stable disease-SD) up to 3 years Occurring during the expansion phase
Safety Phase: time to maximum concentration (Tmax) Up to 3 years Occurring during the safety lead-in phase
Safety Phase: apparent volume of distribution (Vd/F) Up to 3 years Occurring during the safety lead-in phase
Expansion Phase: trough concentration (Ctrough) Up to 3 years Occurring during the expansion phase
Safety Phase: Plasma 2-hydroxyglutarate (2-HG) concentration up to 3 years Occurring during the safety lead-in phase
Safety Phase: AUC over 1 dosing interval at steady state (AUCtau,ss) Up to 3 years Occurring during the safety lead-in phase
Expansion Phase: maximum concentration (Cmax) Up to 3 years Occurring during the expansion phase
Expansion Phase: apparent volume of distribution (Vd/F) Up to 3 years Occurring during the expansion phase
Expansion Phase: apparent clearance (CL/F) Up to 3 years Occurring during the expansion phase
Expansion Phase : area under the concentration-vs-time curve (AUC) from 0 to time of last measurable concentration (AUC0-t) Up to 3 years Occurring during the expansion phase
Expansion Phase: Plasma 2-hydroxygluturate (2-HG) concentration up to 3 years Occurring during the expansion phase
Safety Phase: maximum concentration (Cmax) Up to 3 years Occurring during the safety lead-in phase
Safety Phase: trough concentration (Ctrough) Up to 3 years Occurring during the safety lead-in phase
Expansion Phase: Number of Adverse Events of Special Interests (AESIs) Up to 3 years Occurring during the expansion phase
Expansion Phase: AUC over 1 dosing interval at steady state (AUCtau,ss) Up to 3 years Occurring during the expansion phase
Trial Locations
- Locations (5)
UCSF - Medical Center at Mission Bay
🇺🇸San Francisco, California, United States
Ucsf Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
UCLH
🇬🇧London, United Kingdom