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

NCT06501625 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: S095031-2102024-514261-19-00
• Study Type: interventional
• Target: 52
• Locations: 9 countries
• Sites: 37

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

Outcome Measures

Primary Outcomes (3)

• Safety Lead-in Phase: Number of Dose-limiting toxicities (DLTs)

  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)

  Through 90 days after the end of treatment (Approximately 5 years)

• Expansion Phase: Objective response rate (ORR)

  Confirmed complete response (CR) or confirmed partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Through the end of the study (Approximately 5 years)

Secondary Outcomes (22)

• Safety Lead-in Phase: Ivosidenib Area under the concentration-versus-time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t)

  Through the end of treatment (Approximately 5 years)

• Safety Lead-in Phase: Ivosidenib AUC over 1 dosing interval at steady state (AUCtau,ss)

  Through the end of treatment (Approximately 5 years)

• Safety Lead-in Phase: Ivosidenib time to maximum concentration (Tmax)

  Through the end of treatment (Approximately 5 years)

• Safety Lead-in Phase: Ivosidenib maximum concentration (Cmax)

  Through the end of treatment (Approximately 5 years)

• Safety Lead-in Phase: Ivosidenib trough concentration (Ctrough)

  Through the end of treatment (Approximately 5 years)

Study Arms (2)

Safety Lead-In Phase

EXPERIMENTAL

Drug: Ivosidenib; Drug: Durvalumab (for the first 8, 21-day, cycles); Drug: Gemcitabine (for the first 8, 21-day, cycles); Drug: Cisplatin (for the first 8, 21-day, cycles); Drug: Durvalumab (starting from cycle 9)

Expansion Phase

EXPERIMENTAL

Drug: Durvalumab (for the first 8, 21-day, cycles); Drug: Gemcitabine (for the first 8, 21-day, cycles); Drug: Cisplatin (for the first 8, 21-day, cycles); Drug: Durvalumab (starting from cycle 9); Drug: Ivosidenib Recommended Combination Dose (RCD)

Interventions

Ivosidenib DRUG

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

Safety Lead-In Phase

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

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

Expansion Phase; Safety Lead-In Phase

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

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

Expansion Phase; Safety Lead-In Phase

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

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

Expansion Phase; Safety Lead-In Phase

Durvalumab (starting from cycle 9) DRUG

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

Expansion Phase; Safety Lead-In Phase

Ivosidenib Recommended Combination Dose (RCD) DRUG

RCD administered orally once daily, taken continuously throughout treatment duration

Expansion Phase

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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.)
• chronic skin condition that does not require systemic therapy
• vitiligo

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead

Study Sites (37)

Usc Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Northwestern Medicine

Chicago, Illinois, 60611, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University

Durham, North Carolina, 27708, United States

RECRUITING

Gibbs Cancer Center

Spartanburg, South Carolina, 29303, United States

NOT YET RECRUITING

Tennesse Oncology - Elliston Place Plaza

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas Md Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Alfred Health

Melbourne, 3004, Australia

RECRUITING

Hospital de Amor - Barretos

Barretos, 14784400, Brazil

RECRUITING

Oncoclinicas Mg

Belo Horizonte, 303600680, Brazil

NOT YET RECRUITING

CIONC

Curitiba, 80810050, Brazil

NOT YET RECRUITING

Instituto Dor de Pesquisa E Ensino Sp

São Paulo, 4543000, Brazil

RECRUITING

Princess Margaret Cancer Centre

Toronto, M5G 2C4, Canada

RECRUITING

Institut Bergonie

Bordeaux, 33076, France

RECRUITING

Hôpital Beaujon

Clichy, 92210, France

RECRUITING

Chu Montpellier-Hopital Saint-Eloi

Montpellier, 34295, France

RECRUITING

Charite Universitatsmedizin

Berlin, 13353, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

Universitären Centrums Für Tumorerkrankungen (Uct) Der J.W. Goethe-Universität Frankfurt

Frankfurt, 60488, Germany

RECRUITING

Medizinische Hochschule Hannover Oe 6810

Hanover, 30625, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

National Cancer Center Hospital

Chūōku, 104-0045, Japan

RECRUITING

Kyoto University Hospital

Kyoto, 606-8507, Japan

RECRUITING

Kanagawa Cancer Center

Yokohama, 241-8515, Japan

RECRUITING

Cha Bundang Medical Center

Seongnam, 13496, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

NOT YET RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

NOT YET RECRUITING

Seoul National University Hospital

Seoul, 3080, South Korea

RECRUITING

Severance

Seoul, 3722, South Korea

RECRUITING

Seoul St. Mary'S Hospital

Seoul, 6591, South Korea

RECRUITING

H. Valle de Hebron

Barcelona, 8035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Spain

NOT YET RECRUITING

Hospital Universitario Gregorio Marañón

Madrid, 28007, Spain

RECRUITING

H. 12 de Octubre

Madrid, 28040, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

MeSH Terms

Interventions

ivosidenib; durvalumab; Gemcitabine; Cisplatin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

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

CONTACT

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

Study Design

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

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 15, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): July 23, 2026
• Study Completion (Estimated): September 13, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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

KR (7); JP (4); ES (5); US (7); BR (4); AU (1); DE (5); CA (1); FR (3)