Recruiting

Phase 1

Phase 2

Ivosidenib, Durvalumab, Gemcitabine/CisplatinIvosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Sponsor:

Institut de Recherches Internationales Servier

Code:

NCT06501625

Conditions

Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Ivosidenib

Durvalumab (for the first 8, 21-day, cycles)

Gemcitabine (for the first 8, 21-day, cycles)

Cisplatin (for the first 8, 21-day, cycles)

Durvalumab (starting from cycle 9)

Study Details

Brief summary:

The objective of this study is to investigate the safety, tolerability and preliminary activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy in participants with locally advanced, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation. The study will begin with a safety lead-in phase (Phase 1b study) to determine the recommended combination dose (RDC) and then will transition to an expansion phase (Phase 2 study) to assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RCD. During the treatment period participants will have study visits on days 1, 8, and 15 of Cycle 1, on days 1 and 8 of Cycle 2 to 8, and on day 1 of each additional cycle. Cycles 1 through 8 are 21 day cycles, and each following cycle is 28 days. Approximately 30 days and 90 days after treatment has ended, safety follow-up visits will occur and then participants will be followed for survival every 3 months. Study visits may include blood tests, ECG, vital signs, and a physical examination.

Conditions

Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Study ID

NCT06501625

Start date

Dec 16, 2024

Status verified date

May, 2026

Completion date

Sep 13, 2027

Anticipated

Primary completion date

Jul 23, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Have a histopathological confirmed diagnosis consistent with locally advanced unresectable or metastatic cholangiocarcinoma.
Have documented IDH1 gene-mutated cholangiocarcinoma based on local or central laboratory testing (R132C/L/G/H/S mutation variants tested).
Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
Have adequate bone marrow function as evidenced by:
Absolute neutrophil count ≥ 1,500/mm3 or 1.5 ×109/L
Hemoglobin ≥ 9 g/dL
Platelet count ≥ 100,000/mm3 or 100 × 109/L
Have adequate hepatic function as evidenced by:
Serum bilirubin ≤ 2.0 × the upper limit of normal (ULN); this will not apply to patients with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction should be resolved before randomization
Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5.0 × ULN
Have adequate renal function, defined as: creatinine clearance > 60 mL/min per 24 hour urine or as calculated on the Cockcroft-Gault formula (using actual body weight):

Creatine CL (mL/min)= (140 - Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine (mg/dL)

Exclusion Criteria:

Received treatment for locally advanced, unresectable or metastatic disease with the following exceptions:
Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is permitted before study participation. Note: For the Safety Lead-In Phase, participants who received one prior cycle of durvalumab plus gemcitabine/cisplatin and required dose modifications for treatment-related toxicity are excluded.
Patients who developed recurrent disease > 6 months after surgery with curative intent, and, if given, > 6 months after the completion of adjuvant (chemotherapy and/or radiation).
Prior exposure to immune-mediated therapy, including, but not limited to, anti-PD-1or other anti-PD-L1, and anti-PD-L2, anti-CTLA-4 antibodies, excluding therapeutic anticancer vaccines.
Unresolved Grade ≥2 adverse events from a previous anticancer therapy, with the exception of alopecia and vitiligo and the laboratory values listed in the inclusion criteria.
Patients with Grade ≥2 neuropathy to be evaluated on a case-by-case basis after consultation with the medical monitor
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with ivosidenib may be included only after consultation with the medical monitor
Participation in another interventional study at the same time or within 14 days prior to the first study medication (triple combination treatment) administration. For patients having participated to another prior interventional study, the first dose of ivosidenib should occur after a period greater than or equal to 5 half-lives or 28 days, whichever is shorter of the last dose of the prior investigational product.
Active or prior documented autoimmune or inflammatory disorders including:
inflammatory bowel disease (e.g., colitis or Crohn's disease)
diverticulitis (with the exception of diverticulosis)
systemic lupus erythematosus
Sarcoidosis syndrome
Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)

Note: in cases with no active disease for ≥ 5 years, patients may be considered for inclusion if approved by the Medical Monitor. Participants with the following conditions are eligible for the study:

chronic skin condition that does not require systemic therapy
vitiligo
alopecia
hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy
unmedicated celiac disease that is controlled by diet
Have heart rate-corrected QT interval using Fridericia's formula (QTcF) of ≥ 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome/sudden death, polymorphic ventricular arrhythmia). The Sponsor should review participants with bundle branch block and prolonged QTcF for potential inclusion.
Have an active infection, including:
Hepatitis B (clinical evaluation includes: presence of hepatitis B surface antigen \[HBsAg\] and/or anti-HBcAb with detectable hepatitis B virus \[HBV\] DNA ≥ 10 IU/mL)
Hepatitis C
Tuberculosis (clinical evaluation includes: clinical history, physical examination and/or radiographic findings, and tuberculosis testing as per local practice)
Human immunodeficiency virus (clinical evaluation includes: positive HIV 1/2 antibodies) Note: Patients with a resolved or past HBV infection (i.e., presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) do not need to be excluded from the study. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.

Study Design

Enrollment

52 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Safety Lead-In Phase

experimental: Expansion Phase

Interventions

Ivosidenib

Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration

Durvalumab (for the first 8, 21-day, cycles)

1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles

Gemcitabine (for the first 8, 21-day, cycles)

1000 mg/m2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles

Cisplatin (for the first 8, 21-day, cycles)

25 mg/m\^2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles

Durvalumab (starting from cycle 9)

1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.

Ivosidenib Recommended Combination Dose (RCD)

RCD administered orally once daily, taken continuously throughout treatment duration

Primary outcome measure

Safety Lead-in Phase: Number of Dose-limiting toxicities (DLTs) [ Time Frame: Through Cycle 1 (Cycle 1 is 21 days) ]
Safety Lead-in Phase: Number of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) [ Time Frame: Through 90 days after the end of treatment (Approximately 5 years) ]
Expansion Phase: Objective response rate (ORR) [ Time Frame: Through the end of the study (Approximately 5 years) ]

Central Contacts and Locations

Central contacts

Institut de Recherches Internationales Servier (I.R.I.S.) Clinical Studies Department

+33 1 55 72 60 00 scientificinformation@servier.com

Locations

Cancer and Blood Speciality Clinic - Los Alamitos

Recruiting

Los Alamitos, California, United States, 90720

Usc Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Northwestern Medicine

Recruiting

Chicago, Illinois, United States, 60611

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Duke University

Recruiting

Durham, North Carolina, United States, 27708

Gibbs Cancer Center

Recruiting

Spartanburg, South Carolina, United States, 29303

Tennesse Oncology - Elliston Place Plaza

Recruiting

Nashville, Tennessee, United States, 37203

The University of Texas Md Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Princess Margaret Cancer Centre

Recruiting

Toronto, Canada, M5G 2C4

More Information

Sponsor

Institut de Recherches Internationales Servier

Last update posted

May 11, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Institut de Recherches Internationales Servier on 2026-05-11.