A Phase II Study of Nivolumab Plus Relatlimab 360 mg/360 mg and Gemcitabine/Cisplatin as First-Line Treatment in Patients With Advanced Biliary Tract Cancer.(NOBLE）

National Health Research Institutes, Taiwan8 sites in 1 country76 target enrollmentStarted: May 1, 2026Last updated: January 28, 2026

InterventionsGemcitabine Cisplatin Nivolumab/Relatlimab Nivolumab

Overview

Phase: Phase 2
Status: Not yet recruiting
Sponsor: National Health Research Institutes, Taiwan
Enrollment: 76
Locations: 8
Primary Endpoint: Overall response rate (ORR)

Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Overview

Brief Summary

A Randomized Phase II Study. To assess the difference in objective response rate (ORR) between adult patients with advanced biliary tract cancer assigned to nivolumab plus relatlimab 360 mg/360 mg in combination with GC or nivolumab plus GC as first-line treatment.

Detailed Description

The goal of this clinical trial is to assess the difference in objective response rate (ORR) between adult patients with advanced biliary tract cancer assigned to nivolumab plus relatlimab 360 mg/360 mg in combination with GC or nivolumab plus GC as first-line treatment.

The primary endpoint will be evaluating ORR of nivolumab plus relatlimab 360 mg/360 mg in combination with gemcitabine and cisplatin in patients with advanced BTC.

A total of 76 evaluable subjects will be required for the study, where an evaluable subject is defined as a participant who has at least one post-treatment imaging assessment that is considered evaluable. To account for potential drop-outs or subjects without evaluable post-treatment imaging, the planned enrollment target is approximately 84 subjects, assuming an estimated 10% drop-out rate. After a participant's initial eligibility is established and informed consent has been obtained, the participant will be randomized in a 1:1 ratio to either the nivolumab + relatlimab + GC arm or the nivolumab + GC arm.

Randomization will be stratified by PD-L1 expression (combined positive score [CPS] ≥1 vs <1) and will be centrally assigned using a randomization table. Enrollment will not be restricted by evaluability at the time of registration; however, the number of evaluable subjects will be monitored throughout the trial. If the number of non-evaluable subjects exceeds the anticipated rate, additional participants may be enrolled to ensure that the target of 76 evaluable subjects is achieved.

Eligible patients will receive nivolumab 360 mg or nivolumab 360 mg plus relatlimab 360 mg on Day 1, along with gemcitabine 1000 mg/m² and cisplatin 25 mg/m² on Days 1 and 8 of each 3-week cycle.

Nivolumab and relatlimab will be administered for a maximum of 2 years. Cisplatin will be given for a maximum of 8 cycles. Gemcitabine will be given continuously until disease progression, intolerable toxicity, or patient withdrawal of consent at any time during the study.

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

•histologically confirmed biliary tract carcinoma (including intrahepatic bile duct, extrahepatic bile duct, ampulla of Vater cancer, and gallbladder);
•metastatic or unresectable disease;
•no history of chemotherapy or radiotherapy or immunotherapy for biliary tract cancer, except for patients who experienced recurrence at least six months after completing adjuvant therapy;
•presence of at least one measurable tumor lesion which is defined as lesions that can be accurately measured in at least 1 dimension with longest diameter (LD) ≥20 mm using conventional techniques or ≥10 mm with spiral CT and MRI; measurable lymph nodes must be ≥15 mm in the short axis;
•must have PD-L1 testing with results performed by a local laboratory during the screening period
•adequate hematopoietic function which is defined as below:
•hemoglobin level ≥ 9 g/dL;
•absolute neutrophil count (ANC) ≥ 1,500/mm3;
•platelet count ≥ 100,000/mm3;
•adequate hepatic function which is defined as below:

Exclusion Criteria

•other malignancy within the past 2 years except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ;
•history or known presence of brain metastasis;
•presence of grade 2 or above ascites or pleural effusion;
•presence of grade 2 or above diarrhea;
•presence of mental disease or psychotic manifestation;
•active or uncontrolled infection;
•Significant medical conditions that are contraindicated to study medication or render the patient at high risk from treatment complications, such as: Biliary tract-related infection or sepsis. Uncontrolled biliary obstruction. Ongoing grade ≥2 infection at any site despite appropriate therapy.;
•Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
•Myocardial infarction (MI) or stroke/transient ischemic attack within the 6 months prior to consent
•Uncontrolled angina within the 3 months prior to consent