Ivosidenib plus lenvatinib or PD‑1/PD‑L1 therapy for IDH1‑mutant advanced biliary tract cancer

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 trial will try combining ivosidenib with either lenvatinib or a PD‑1/PD‑L1 immunotherapy in people with advanced biliary tract cancer who have an IDH1 mutation and whose disease progressed after chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Drugs / interventions: lenvatinib, chemotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT07282262 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open‑label, non‑randomized phase II umbrella trial using next‑generation sequencing to identify patients with IDH1‑mutant advanced biliary tract cancers. Eligible patients have measurable disease by RECIST 1.1, ECOG 0–1, and prior systemic chemotherapy failure; patients are assigned to receive ivosidenib combined with either a multi‑target tyrosine kinase inhibitor (represented by lenvatinib) or a PD‑1/PD‑L1 inhibitor. The study will follow participants for tumor responses, progression‑free survival, overall survival signals, and treatment‑related adverse events. Treatment effects and safety will be reported for each combination arm to explore whether adding targeted or immune therapy to ivosidenib improves outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced or metastatic biliary tract cancer harboring an IDH1 mutation, measurable disease, ECOG performance status 0–1, adequate organ function, and prior systemic chemotherapy failure.

Not a fit: Patients without an IDH1 mutation, those previously treated with ivosidenib, people with ampulla of Vater cancer, pregnant or breastfeeding individuals, or those with poor performance status or major organ dysfunction are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combinations could offer a more effective targeted treatment option that slows tumor growth and extends time without progression for IDH1‑mutant biliary tract cancer after chemotherapy.

How similar studies have performed: Single‑agent ivosidenib has previously shown clinical benefit in IDH1‑mutant cholangiocarcinoma, but combining ivosidenib with TKIs or PD‑1/PD‑L1 inhibitors remains exploratory with limited prior data.

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.

Where this trial is running

Beijing

• Beijing Peking Union Medical College Hospital Outpatient Department — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Chengjie Li

Conditions Biliary Tract Cancer