Gemcitabine-Cisplatin Plus Envafolimab in Resectable Biliary Tract Malignancies

NCT07599995 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SRRSH
• Study Type: interventional
• Target: 34
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial is to evaluate the efficacy of Gemcitabine-Cisplatin (GC) plus Envafolimab neoadjuvant therapy in the patients at high risk of recurrence. Primary endpoint: Major Pathologic Response (MPR). It will also learn about the safety of drug including Gemcitabine-Cisplatin (GC) plus Envafolimab as a neoadjuvant therapy in this trial.

Conditions

Biliary Tract Cancer

Keywords

Resectable Biliary Tract Cancer; High Risk of Recurrence

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response (MPR)

  MPR is defined as ≤10% residual viable tumor cells in the primary lesion and regional lymph nodes following neoadjuvant therapy, with Pathologic Response Rate (PCR, 0% viable tumor cells) included in the MPR definition.

  From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

Secondary Outcomes (6)

• Residual viable tumor cell ratio

  From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

• Objective Response Rate (ORR)

  From enrollment until 2-4 weeks after completion of neoadjuvant therapy (three cycles, each cycle is 21 days)

• Pathologic Response Rate (PCR)

  From enrollment to 2-4 weeks after completion of thrid cycle (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

• R0 resection

  From enrollment to 2-4 weeks after completion of thrid cycles (each cycle is 21 days) of neoadjuvant therapy, surgical pathological findings will be obtained, or patients will be assessed as unresectable.

• Overall Survival (OS)

  From enrollment up to 2 years following treatment initiation

Other Outcomes (1)

• Biomarker Evaluation

  From enrollment until 2 years after treatment

Study Arms (1)

GC Chemotherapy Plus Envafolimab Arm

EXPERIMENTAL

Participants first receive GC chemotherapy plus envafolimab every 3 weeks (Q3W) for a total of 3 cycles (each cycle is 21 days). Eligibility for surgery is then assessed; eligible patients undergo radical resection.

Drug: Neoadjuvant therapy followed by surgery

Interventions

Neoadjuvant therapy followed by surgery DRUG

First: Envafolimab: 400 mg on Day 1, repeated every 3 weeks (Q3W). GC chemotherapy: Gemcitabine: 1000 mg/m2 in 100 mL of 0.9% sodium chloride injection, administered intravenously over 30 minutes on Days 1 and 8, repeated Q3W. Cisplatin: 25 mg/m2 in 500 mL of 5% glucose injection, administered intravenously over 2 hours on Day 1 and 8, repeated Q3W. Of note, no target drugs is involved. Second: Radical resection eligibility will be assessed by the investigator; those with indeterminate resectability require additional MDT discussion confirmation. The criteria for radical resection: 1. No invasion of the main trunk of the hepatic vein, portal vein, or inferior vena cava; 2. No distant metastasis except for hilar lymph node metastases; 3. Minimum distance between surgical margin and tumor border ≥ 0.5 cm; 4. Residual liver volume ≥ 30% (≥ 40% for participants with cirrhosis).

Also known as: Envafolimab, Gemcitabine, Cisplatin; Neoadjuvant GC-Envafolimab for Resectable Biliary Tract Malignancies

GC Chemotherapy Plus Envafolimab Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who have signed a written Informed Consent Form (ICF);
• Male or female participants aged 18-80 years;
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0/1;
• Biliary Tract Cancer (BTC) diagnosed by puncture pathology prior to enrollment;
• Participants must meet the following requirements for major vital organ function: a. Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count ≥ 90×10⁹/L; hemoglobin ≥ 9 g/dL; b. Coagulation function: international normalized ratio (INR) ≤ 1.2; c. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 times the upper limit of normal (ULN); d. Serum albumin ≥ 3.5 g/dL; total bilirubin ≤ 1.5 times the ULN. Patients with obstructive jaundice who meet the eligibility criteria after percutaneous transhepatic cholangial drainage or endoscopic retrograde cholangiopancreatography treatment are also eligible for enrollment; e. Child-Pugh class A or B; f. Serum creatinine ≤ 1.5 times the ULN;
• Patients with high-risk factors for recurrence. The criteria are defined as meeting at least one of the following: a. Preoperative CA19-9 ≥ 200 U/mL; b. Tumor diameter ≥ 5 cm or multiple tumor nodules on imaging; c. Regional lymph node metastasis with a short-axis diameter ≥ 1.0 cm on imaging; d. Vascular invasion (portal vein or hepatic artery) on imaging; e. Low or undifferentiated histologic grade;
• Participants who have at least 1 measurable lesion (RECIST v1.1);
• Be able to provide fresh stool samples and liver samples if undergoing surgery.

You may not qualify if:

• Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma, and other non-cholangiocarcinoma malignant tumor components;
• Prior systemic therapy for BTC, including immunotherapy, targeted therapy, or chemotherapy;
• History of other prior or concurrent malignancies, except those with complete treatment and disease-free survival for more than 5 years;
• Presence of an active, known or suspected autoimmune disease, or requirement for long-term systemic corticosteroid therapy (equivalent to ≥ 10 mg prednisone daily) or other immunosuppressive agents. Participants using inhaled or topical corticosteroids will not be excluded;
• Presence of ascites, hepatic encephalopathy, sclerosing cholangitis, or other concurrent organ dysfunctions that would preclude tolerance of general anesthesia or hepatectomy;
• Women who are breastfeeding or pregnant;
• Any other factors that, in the investigator's judgment, may compromise participant safety or trial compliance, including serious comorbidities requiring ongoing treatment, clinically significant laboratory abnormalities, or relevant social or family-related issues.

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead

Related Publications (12)

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• Le Roy B, Gelli M, Pittau G, Allard MA, Pereira B, Serji B, Vibert E, Castaing D, Adam R, Cherqui D, Sa Cunha A. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Br J Surg. 2018 Jun;105(7):839-847. doi: 10.1002/bjs.10641. Epub 2017 Aug 31.

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• 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.

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• Pereira RA, Barcellos G, Lenz G, Pereira AAL, Biachi de Castria T. Neoadjuvant Chemotherapy in Resectable Biliary Tract Cancer: A Systematic Review and Metanalysis. J Surg Oncol. 2026 Mar;133(3):313-325. doi: 10.1002/jso.70169. Epub 2025 Dec 22.

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• Chen C, Chen Z, Chen D, Zhang B, Wang Z, Le H. Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer. J Int Med Res. 2015 Apr;43(2):180-7. doi: 10.1177/0300060514561504. Epub 2015 Feb 6.

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• Chen Y, Zhang J, Hu W, Li X, Sun K, Shen Y, Zhang M, Wu J, Gao S, Yu J, Que R, Zhang Y, Yang F, Xia W, Zhang A, Tang X, Bai X, Liang T. Envafolimab plus lenvatinib and transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a prospective, single-arm, phase II study. Signal Transduct Target Ther. 2024 Oct 9;9(1):280. doi: 10.1038/s41392-024-01991-1.

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• Shi GM, Huang XY, Liang F, Liang X, Dong R, Ye QH, Gao Q, Ji Y, Yu ZP, Zhai WL, Lu JC, Li XW, Liu FB, Wang K, Yang W, Zhang JL, Hu ZQ, Qiu SJ, Wang XY, Yang XR, Sun HC, Shi YH, Ding ZB, Liu WR, Huang XW, Huang C, Shen YH, Sun J, He YF, Peng YF, Xu Y, Zou JJ, Zhou J, Fan J; ZSAB Study Group. Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma. N Engl J Med. 2026 Mar 5;394(10):983-995. doi: 10.1056/NEJMoa2513918.

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MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

envafolimab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yuelong Liang, Ph.D

  Sir Run Run Shaw Hospital, Schoole of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yifan Tong, Ph.D

CONTACT

86 571 86006271; tongyf@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of General Surgery of Dayunhe Campus, Principal Investigator, Clinical Professor

Model Details: The detailed schedule for each cycle is as follows: 1) Envafolimab: 400 mg on Day 1, repeated every 3 weeks (Q3W). 2) GC chemotherapy: Gemcitabine: 1000 mg/m2 in 100 mL of 0.9% sodium chloride injection, administered intravenously over 30 minutes on Days 1 and 8, repeated Q3W. Cisplatin: 25 mg/m2 in 500 mL of 5% glucose injection, administered intravenously over 2 hours on Day 1 and 8, repeated Q3W.

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: May 20, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2030
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After study completion and publication of study results
• Access Criteria: Medical institutions \& personnel, non-commercial use