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.

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.

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: Ivosidenib; Drug: Lenvatinib; Biological: PD-1/PD-L1 inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chengjie Li; Phone Number: 13733879582; Email: 1624271942@qq.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Peking Union Medical College Hospital Outpatient Department
    • Contact: Principal Investigator; Phone Number: +86-10-69152830; Email: zhaoht@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivosidenib Monotherapy	Drug: 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.
Experimental: Ivosidenib + Lenvatinib	Drug: 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.; 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.
Experimental: Ivosidenib + PD-1/PD-L1 Inhibitor	Drug: 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.; Biological: 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.
Experimental: Ivosidenib + Lenvatinib + PD-1/PD-L1 Inhibitor	Drug: 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.; 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.; Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	From first dose of study drug until disease progression, death, or start of new anti-cancer therapy, assessed up to approximately 24 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease Control Rate (DCR)	From first dose of study drug until disease progression, death, or start of new anti-cancer therapy, assessed up to approximately 24 months.
Progression-Free Survival (PFS)	From first dose of study drug until disease progression or death from any cause (whichever occurs first), assessed up to approximately 24 months.
Overall Survival (OS)	From enrollment (or first dose) until death from any cause, assessed up to approximately 36 months.
Duration of Response (DOR)	From the date of first documented response (CR or PR) until the date of disease progression or death, assessed up to approximately 24 months.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors; lenvatinib; ivosidenib
• Other Study ID Numbers: NBLF001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No