An Exploratory Study on the Use of Ivosidenib for the Precise Treatment of Advanced Biliary Tract Malignancies With IDH1 Mutations in the Later Line of Therapy.

NCT ID: NCT07282262

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2026-10-01

Brief Summary

This is a multicenter, non-randomized, umbrella, open-label phase II clinical study, aiming to observe and evaluate, as well as explore the efficacy and safety of precision targeted therapy based on NGS technology for IDH1-mutated patients, specifically the combination of ivosidenib with multi-target tyrosine kinase inhibitors represented by lenvatinib or PD-1/PD-L1 in advanced biliary tract cancer patients who have failed systemic chemotherapy.

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ivosidenib Monotherapy

Group Type: EXPERIMENTAL

Ivosidenib

Intervention Type: DRUG

Oral, selective, small-molecule inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Administered at a dose of 500 mg, taken orally once daily. This is the core investigational drug in all study arms.

Ivosidenib + Lenvatinib

Group Type: EXPERIMENTAL

Ivosidenib

Intervention Type: DRUG

Oral, selective, small-molecule inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Administered at a dose of 500 mg, taken orally once daily. This is the core investigational drug in all study arms.

Lenvatinib

Intervention Type: DRUG

Oral, multi-targeted tyrosine kinase inhibitor. Administered at a weight-based dose (8 mg for body weight \<60 kg or 12 mg for body weight ≥60 kg), taken orally once daily. Used in combination arms.

Ivosidenib + PD-1/PD-L1 Inhibitor

Group Type: EXPERIMENTAL

Ivosidenib

Intervention Type: DRUG

Oral, selective, small-molecule inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Administered at a dose of 500 mg, taken orally once daily. This is the core investigational drug in all study arms.

PD-1/PD-L1 inhibitor

Intervention Type: BIOLOGICAL

Intravenous immune checkpoint inhibitor. Specific agent (e.g., Pembrolizumab, Durvalumab, Toripalimab, or Tislelizumab) may be chosen based on local availability and patient access. Administered at standard doses (e.g., 200 mg, 1500 mg, or 240 mg) via IV infusion every three weeks. Used in combination arms.

Ivosidenib + Lenvatinib + PD-1/PD-L1 Inhibitor

Group Type: EXPERIMENTAL

Ivosidenib

Intervention Type: DRUG

Oral, selective, small-molecule inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Administered at a dose of 500 mg, taken orally once daily. This is the core investigational drug in all study arms.

Lenvatinib

Intervention Type: DRUG

Oral, multi-targeted tyrosine kinase inhibitor. Administered at a weight-based dose (8 mg for body weight \<60 kg or 12 mg for body weight ≥60 kg), taken orally once daily. Used in combination arms.

PD-1/PD-L1 inhibitor

Intervention Type: BIOLOGICAL

Intravenous immune checkpoint inhibitor. Specific agent (e.g., Pembrolizumab, Durvalumab, Toripalimab, or Tislelizumab) may be chosen based on local availability and patient access. Administered at standard doses (e.g., 200 mg, 1500 mg, or 240 mg) via IV infusion every three weeks. Used in combination arms.

Interventions

Ivosidenib

Oral, selective, small-molecule inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Administered at a dose of 500 mg, taken orally once daily. This is the core investigational drug in all study arms.

Intervention Type: DRUG

Lenvatinib

Oral, multi-targeted tyrosine kinase inhibitor. Administered at a weight-based dose (8 mg for body weight \<60 kg or 12 mg for body weight ≥60 kg), taken orally once daily. Used in combination arms.

Intervention Type: DRUG

PD-1/PD-L1 inhibitor

Intravenous immune checkpoint inhibitor. Specific agent (e.g., Pembrolizumab, Durvalumab, Toripalimab, or Tislelizumab) may be chosen based on local availability and patient access. Administered at standard doses (e.g., 200 mg, 1500 mg, or 240 mg) via IV infusion every three weeks. Used in combination arms.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Voluntary Participation: Signed informed consent.
• Genetic Mutation: Presence of an IDH1 mutation confirmed by genetic testing.
• Disease Status：
• Newly diagnosed, untreated advanced/metastatic disease; OR
• Recurrence >6 months after curative-intent surgery (with or without adjuvant therapy).
• Measurable Disease: At least one measurable lesion per RECIST 1.1.
• Performance Status: ECOG performance status of 0 or 1.
• Life Expectancy： ≥3 months.
• Organ Function: Adequate hematological, hepatic, and renal function.
• Contraception: Use of highly effective contraception for women of childbearing potential and men.

Exclusion Criteria

• Prior Treatment: Previous treatment with Ivosidenib.
• Cancer Type: Ampulla of Vater cancer.
• Pregnancy： Pregnant or breastfeeding women.
• Allergy: Known hypersensitivity to any component of the study drugs.
• Recent Therapy: Local anti-tumor therapy or major surgery within 4 weeks prior to initiation.
• Medical Conditions:
• Uncontrolled hypertension.
• Significant cardiovascular disease.
• Active or untreated CNS metastases.
• Active autoimmune disease.
• Uncontrolled active infection (e.g., HBV, HCV, HIV).
• Significant bleeding tendency or history.
• Severe non-healing wounds.
• History of organ transplantation.
• Concurrent Participation: Participation in another interventional clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Peking Union Medical College Hospital Outpatient Department

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Chengjie Li

Role: CONTACT

1624271942@qq.com

13733879582

Facility Contacts

Principal Investigator

Role: primary

zhaoht@pumch.cn

+86-10-69152830

Other Identifiers

NBLF001

Identifier Type: -

Identifier Source: org_study_id