Gemcitabine and Nab-Paclitaxel Combined With Iparomlimab and Tuvorilimab for Advanced Gallbladder Cancer (TRANSFORM-GBC)

A Phase II, Single-Arm, Multicenter Study of Gemcitabine and Nab-Paclitaxel in Combination With Iparomlimab and Tuvorilimab in Patients With Advanced Gallbladder Cancer

This is a single-arm, multicenter, Phase II clinical trial evaluating the efficacy and safety of Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorilimab (a dual anti-PD-1/CTLA-4 bispecific antibody) in patients with advanced unresectable gallbladder cancer.

The study aims to assess the surgical conversion rate and objective response rate (ORR) as primary endpoints. Secondary endpoints include R0 resection rate, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profiles.

A total of 44 participants will be enrolled across three centers in China. The study is scheduled to run from May 2025 to April 2027.

Study Overview

• Status: Enrolling by invitation
• Conditions: Gallbladder Cancer Unresectable
• Intervention / Treatment: Drug: Treatment :Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorili

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200092
      • Xinhua hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent.
• Age 18-75 years.
• ECOG performance status 0-2, Child-Pugh class A.
• Histologically or cytologically confirmed advanced gallbladder cancer, deemed unresectable for R0 resection.
• Adequate organ function:
• ANC ≥1.5×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥90 g/L.
• Serum creatinine ≤1.2 mg/dL or creatinine clearance ≥60 mL/min.
• Total bilirubin ≤1.5×ULN (≤3×ULN if liver metastases); AST/ALT ≤3×ULN (≤5×ULN if liver metastases).
• Life expectancy ≥3 months.
• Non-pregnant, non-lactating women and willingness to use contraception during and for 3 months after treatment.

Exclusion Criteria:

• Severe systemic infection or uncontrolled comorbidities (e.g., heart failure, thyroid disease, psychiatric disorders); active autoimmune disease requiring medication.
• Known allergy or intolerance to chemotherapy agents.
• Prior antitumor therapy (chemotherapy, radiotherapy, immunotherapy) within the past year, or history of other malignancies (except cured cervical carcinoma in situ or non-melanoma skin cancer).
• Pregnancy, lactation, or unwillingness to use contraception.
• Participation in another clinical trial within 30 days before the first dose.
• Unwillingness to participate or inability to provide informed consent.
• Any other condition that, in the investigator's judgment, may affect patient safety or compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment :Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorili	Drug: Treatment :Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorili; Treatment :Gemcitabine plus Nab-Paclitaxel (AG regimen) in combination with Iparomlimab and Tuvorili

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	The objective response rate (ORR) of this quadruplet regimen as first-line therapy	At the end of Cycle 6 (each cycle is 21 days)
Surgical Conversion Rate	Proportion of patients who achieve successful conversion to radical resection (R0/R1) after systemic therapy.	At the end of Cycle 6 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Downstaging Rate	Proportion of patients whose clinical stage is reduced after conversion therapy.	At the end of Cycle 6 (each cycle is 21 days)
Pathologic Response Rate	Proportion of patients with pathologic downstaging or major pathologic response in resected specimens	At the end of Cycle 6 (each cycle is 21 days)
R0 Resection Rate	Proportion of patients who undergo R0 resection among those who receive surgery.	At the end of Cycle 6 (each cycle is 21 days)
Disease Control Rate (DCR)	Proportion of patients with CR, PR, or stable disease (SD) lasting ≥4 weeks.	At the end of Cycle 6 (each cycle is 21 days)
Recurrence-Free Survival (RFS)	Proportion of patients without recurrence at 2 years after resection.	up to 2 years
Overall Survival (OS)	Time from enrollment to death from any cause.	through study completion,up to 3 years
Adverse Events (AEs) / Serious AEs (SAEs)	Incidence and severity of AEs and SAEs graded by CTCAE v5.0.	through study completion, up to 30 days
Surgical Safety	Incidence of surgery-related complications (e.g., infection, bleeding, organ dysfunction)	Perioperative

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Wei Gong, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: gallbladder cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Gallbladder Diseases; Biliary Tract Neoplasms; Gallbladder Neoplasms; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: XHEC-C-2025-111-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No