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.

NCT07282262 | Recruiting Phase 2 DMC

• 1 other identifier: NBLF001
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

Study Arms (4)

Ivosidenib Monotherapy

EXPERIMENTAL

Drug: Ivosidenib

Ivosidenib + Lenvatinib

EXPERIMENTAL

Drug: Ivosidenib; Drug: Lenvatinib

Ivosidenib + PD-1/PD-L1 Inhibitor

EXPERIMENTAL

Drug: Ivosidenib; Biological: PD-1/PD-L1 inhibitor

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

EXPERIMENTAL

Drug: Ivosidenib; Drug: Lenvatinib; Biological: PD-1/PD-L1 inhibitor

Interventions

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

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

PD-1/PD-L1 inhibitor 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; Ivosidenib + PD-1/PD-L1 Inhibitor

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Beijing Peking Union Medical College Hospital Outpatient Department

Beijing, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

ivosidenib; lenvatinib; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Chengjie Li

CONTACT

13733879582; 1624271942@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: December 15, 2025
• Study Start: May 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)