Anti-PD-1/PD-L1 Antibodies Plus Gemcitabine and Cisplatin for Advanced CCA

A Phase I/II Study of Anti-PD-1/PD-L1 Antibodies in Combination With Gemcitabine and Cisplatin for Patients With Advanced Cholangiocarcinoma

This study is a prospective, observational study designed to analyze the safety, tolerability, and efficacy of first-line treatment using the combination of gemcitabine and cisplatin plus anti-PD-1/PD-L1 antibodies for patients with advanced cholangiocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: Anti-PD-1/PD-L1 antibody; Drug: Gemcitabine and Cisplatin Chemotherapy

Detailed Description

This is a prospective cohort study of combination anti-PD-1/PD-L1 antibodies plus Gemcitabine and Cisplatin chemotherapy for adult patients (≥18) with advanced cholangiocarcinoma

Gemcitabine and Cisplatin (GC): This chemotherapy doublet has been the historical standard of care for advanced cholangiocarcinoma. It works by interfering with DNA synthesis and causing DNA cross-linking, leading to tumor cell apoptosis.

Anti-PD-1/PD-L1 antibodies: Immunotherapy (including pembrolizumab, durvalumab, envafolimab, tislelizumab, etc.) is designed to block the PD-1/PD-L1 immune checkpoint pathway, thereby reinvigorating T-cells to recognize and attack tumor cells. Recent pivotal trials (e.g., TOPAZ-1, KEYNOTE-966) have demonstrated that adding immunotherapy to GC chemotherapy significantly improves overall survival compared to chemotherapy alone.

This study aims to evaluate the real-world safety, tolerability, and clinical efficacy of this combination regimen in specific clinical practice settings for unresectable late-stage cholangiocarcinoma patients.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Qinghai Ye, PhD; Phone Number: 2164041990; Email: 24111210117@m.fudan.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • ZhongShan Hospital FuDan University
      • Contact: Hui Li, PhD; Phone Number: 13075929630; Email: vincentxwx34@163.com
      • Contact: Email: 24111210117@m.fudan.edu.cn
      • Sub-Investigator: Wenxin Xu, PhD
      • Sub-Investigator: Mincheng Yu, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients with locally advanced or metastatic biliary tract cancer diagnosed histologically or cytologically.

Description

Inclusion Criteria:

• 1. ≥18 years old, male or female 2. Histologically or cytologically confirmed locally advanced or metastatic biliary tract cancer (including ICC, ECC, or GBC) that is not amenable to curative surgery or local therapies.

  3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 4. Patient has given written informed consent. 5. The function of important organs meets the requirements 6. Expected survival ≥12 weeks 7. Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period.

Exclusion Criteria:

• 1. The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included); 2. The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment; 3. Have clinical symptoms or disease that are not well controlled; 4. Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization; 5. Arterial/venous thrombosis in the first 6 months of randomization 6. According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.#with family or social factors, it will affect the safety of patients. 7. Known hypersensitivity to Gemcitabine, Cisplatin, or platinum-containing compounds; significant hearing impairment (grade ≥2) or peripheral neuropathy (grade ≥2) that contraindicates Cisplatin;

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chemotherapy plus Immunotherapy Combination	Drug: Anti-PD-1/PD-L1 antibody; Anti-PD-1/PD-L1 Intravenous injection for at least 6 months; Drug: Gemcitabine and Cisplatin Chemotherapy; Gemcitabine and cisplatin Intravenous injection for at least 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Safety will be monitored by addressing and recording all adverse events (AEs), serious adverse events (SAEs) and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.	Up to 30 days after last treatment dose
Objective response rate(ORR)	Evaluated by researchers based on the RECIST 1.1 standard	5 years
Progression free survival(PFS)	Evaluated by researchers based on the RECIST 1.1 standard	5 years
Duration of relief(DOR)	Evaluated by researchers based on the RECIST 1.1 standard	5 years
To the relief time (TOR)	Evaluated by researchers based on the RECIST 1.1 standard	Time Frame: 5 years
Disease Control Rate (DCR)	Evaluated by researchers based on the RECIST 1.1 standard	Time Frame: 5 years

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Publications and helpful links

General Publications

• Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.
• Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.
• Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, Kim JW, Suksombooncharoen T, Ah Lee M, Kitano M, Burris H, Bouattour M, Tanasanvimon S, McNamara MG, Zaucha R, Avallone A, Tan B, Cundom J, Lee CK, Takahashi H, Ikeda M, Chen JS, Wang J, Makowsky M, Rokutanda N, He P, Kurland JF, Cohen G, Valle JW. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022 Aug;1(8):EVIDoa2200015. doi: 10.1056/EVIDoa2200015. Epub 2022 Jun 1.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 6, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 6, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Gemcitabine; Cisplatin; Cholangiocarcinoma; Anti-PD-1/PD-L1 antibody
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine
• Other Study ID Numbers: Y2024-752

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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