IDH1-mutant Cholangiocarcinoma
Conditions
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.
Interventions
DRUGIvosidenib
ivosidenib taken once daily
DRUGNivolumab
Nivolumab taken by intravenous infusion
DRUGIpilimumab
Ipilimumab taken by intravenous infusion
Sponsors
Servier Bio-Innovation LLC
Institut de Recherches Internationales Servier
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Lead-In 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 |
| Safety Lead-In Phase: Number of Adverse Events (AEs) | 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) | Through study termination (approximately 1 year) | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: Number of Serious Adverse Events (SAEs) | Through study termination (approximately 1 year) | Occurring during the safety lead-in phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: Plasma 2-hydroxyglutarate (2-HG) Concentration | up to 3 years | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: AUC Over 1 Dosing Interval at Steady State (AUCtau,ss) | Up to 3 years | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: Time to Maximum Concentration (Tmax) | Up to 3 years | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: Maximum Concentration (Cmax) | Up to 3 years | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: Trough Concentration (Ctrough) | Up to 3 years | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: Apparent Volume of Distribution (Vd/F) | Up to 3 years | Occurring during the safety lead-in phase |
| Safety Lead-In Phase: Apparent Clearance (CL/F) | Up to 3 years | Occurring during the safety lead-in phase |
Countries
United Kingdom, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 18.12 |
| Age, Customized < 65 years | 4 Participants |
| Age, Customized ≥ 65 years | 3 Participants |
| BMI | 23.33 kg/m^2 STANDARD_DEVIATION 2.114 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 Participants |
| Race/Ethnicity, Customized White | 6 Participants |
| Region of Enrollment United Kingdom | 2 participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 2 / 3 |
| other Total, other adverse events | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 3 / 4 | 2 / 3 |
Outcome results
None listed