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.

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 2

Conditions: Biliary Tract Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07282262

NBLF001

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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300 participants in 4 patient groups

Ivosidenib Monotherapy

Experimental group

Treatment:

Drug: Ivosidenib

Ivosidenib + Lenvatinib

Experimental group

Treatment:

Drug: Lenvatinib

Drug: Ivosidenib

Ivosidenib + PD-1/PD-L1 Inhibitor

Experimental group

Treatment:

Biological: PD-1/PD-L1 inhibitor

Drug: Ivosidenib

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

Experimental group

Treatment:

Biological: PD-1/PD-L1 inhibitor

Drug: Lenvatinib

Drug: Ivosidenib