Combination Therapy of GCNT and Tislelizumab in Advanced Biliary Tract Cancer (GemCiNT)

Recruiting

• Conditions: Locally Advanced Biliary Tract Cancers; Metastatic Biliary Tract Cancers
• Interventions: Drug: Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.

• Registration Number: NCT06893380
• Lead Sponsor: CHA University

Brief Summary

This is a multicenter Phase 1b/2 clinical trial investigating the efficacy and safety of a combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic biliary tract cancers (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.

The Phase 1b portion aims to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Nab-paclitaxel in combination with Gemcitabine, Cisplatin, and Tislelizumab. In the Phase 2 portion, the study will evaluate the Objective Response Rate (ORR) as the primary endpoint, with additional assessments of Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), and Quality of Life (QoL). Safety and tolerability will also be closely monitored.

This study seeks to leverage the stromal-disrupting effect of Nab-paclitaxel and the immune checkpoint blockade effect of Tislelizumab, combined with the established chemotherapy backbone of Gemcitabine and Cisplatin, to enhance treatment outcomes for BTC patients. The study will enroll patients across three medical centers in South Korea, including CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.

Detailed Description

Biliary tract cancer (BTC) is a heterogeneous group of malignancies arising from the biliary epithelium, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Most patients are diagnosed at unresectable, locally advanced, or metastatic stages, and the prognosis remains poor despite advances in systemic therapy.

Since the ABC-02 trial established Gemcitabine plus Cisplatin as the standard first-line chemotherapy for advanced BTC, numerous combination strategies have been explored to improve survival outcomes. In particular, the addition of Nab-paclitaxel to Gemcitabine and Cisplatin has shown promising efficacy by enhancing stromal penetration and drug delivery, supported by preclinical and early clinical studies.

More recently, immune checkpoint inhibitors (ICIs) have emerged as a new treatment option for BTC. The TOPAZ-1 trial demonstrated that adding Durvalumab to Gemcitabine and Cisplatin significantly improved Overall Survival (OS), establishing immunotherapy-based combination therapy as a new standard of care for advanced BTC. Similarly, the KEYNOTE-966 trial confirmed the benefit of Pembrolizumab combined with Gemcitabine and Cisplatin, further supporting the role of ICIs in BTC management.

Tislelizumab, a humanized PD-1 monoclonal antibody, has shown efficacy in various solid tumors and is now being evaluated in BTC. Compared to other PD-1 inhibitors, Tislelizumab was designed to minimize Fc receptor binding, potentially reducing off-target immune activation and enhancing anti-tumor immune response. Combining Tislelizumab with cytotoxic chemotherapy, including Nab-paclitaxel, may offer synergistic benefits by enhancing antigen release and promoting immune response within the tumor microenvironment.

This Phase 1b/2 multicenter trial aims to investigate the safety, tolerability, and efficacy of the combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic BTC. The study will be conducted across three medical centers in South Korea: CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.

The Phase 1b part will determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Nab-paclitaxel when combined with Gemcitabine, Cisplatin, and Tislelizumab. Dose escalation will follow a standard 3+3 design, with dose-limiting toxicities (DLTs) assessed during Cycle 1.

In the Phase 2 part, the primary endpoint will be Objective Response Rate (ORR), with secondary endpoints including Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), and Quality of Life (QoL) assessed using EORTC QLQ-C30 and QLQ-BIL21. Safety and tolerability will also be evaluated throughout the study.

This study seeks to optimize the therapeutic potential of chemotherapy plus immunotherapy by incorporating Nab-paclitaxel at a reduced dose to enhance tolerability while maintaining efficacy. Exploratory objectives include assessing immunological and metabolic changes induced by the study drugs, as well as collecting tumor and blood samples for future biomarker analyses.

Through this trial, we aim to establish a novel first-line treatment strategy for advanced BTC, potentially improving survival outcomes beyond the current standard of care.

Study Timeline

• Study Start: 2024-10-01
• Status Verified: 2025-03
• Study First Submitted: 2025-03-12
• Study First Submitted QC: 2025-03-18
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-30
• Last Update Posted: 2025-04-03
• Primary Completion: 2025-05-24
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Combination Therapy Group	Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.	This group consists of patients with unresectable, locally advanced, or metastatic biliary tract cancer who will receive combination therapy with Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 24 months after treatment initiation.	The proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 36 months after treatment initiation.	Time from the date of first dose to the date of death from any cause.
Progression-Free Survival (PFS)	Up to 24 months after treatment initiation.	Time from the date of first dose to disease progression per RECIST v1.1 or death from any cause.
Disease Control Rate (DCR)	Up to 24 months after treatment initiation.	The proportion of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1.
Duration of Response (DOR)	Up to 24 months after treatment initiation.	Time from first documented response (CR or PR) to progression or death.
Quality of Life (QoL)- EORTC QLQ-C30	Up to 24 months after treatment initiation.	Patient-reported quality of life assessed using the EORTC QLQ-C30 questionnaire.
Quality of Life (QoL)- EORTC QLQ-BIL21	Up to 24 months after treatment initiation.	Patient-reported quality of life assessed using the EORTC QLQ-BIL21 questionnaire.
Safety and Tolerability	Up to 30 days after last dose.	Incidence, severity, and type of adverse events (AEs), graded per NCI CTCAE v5.0.

Trial Locations

Locations (1)

CHA Bundang Medical Center; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of