A Phase II Exploratory Study of Sacituzumab Tirumotecan Combined With Envafolimab for TROP2-Positive Advanced Biliary Tract Cancers Previously Treated With First-Line Immunotherapy Combined With Chemotherapy.

This is a prospective, single-arm, Phase II study evaluating sacituzumab tirumotecan combined with envafolimab in patients with TROP2-positive advanced biliary tract cancers who have progressed on first-line immunochemotherapy. Up to 28 eligible patients will be enrolled.After screening, eligible patients receive sacituzumab tirumotecan (5 mg/kg IV, d1, Q2W) plus envafolimab (300 mg SC, d1, Q2W) for 3 cycles, with subsequent treatment at the investigator's discretion.

Tumor imaging assessments per RECIST v1.1 are performed at Week 6, then every 6 weeks (up to 48 weeks) and every 12 weeks (thereafter) until disease progression, new therapy, loss to follow-up, or death. Post-treatment survival follow-up is conducted by phone every 3 months.

The study includes a safety run-in (6 patients) followed by an expansion phase using Simon's two-stage design (first stage: 15 patients; second stage: total 28 patients). The safety run-in stops if >2 DLTs occur; expansion proceeds if ≤2 DLTs. The trial is terminated if ≤1 objective response is observed in the first 15 expansion patients.

The primary endpoint is ORR(investigator-assessed per RECIST v1.1). Secondary endpoints include OS, PFS, DCR, DOR, safety, and tolerability.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Biliary Tract Cancers
• Intervention / Treatment: Drug: Sacituzumab tirumotecan combined with envafolimab

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Huikai Li; Phone Number: +86 18622228639; Email: tjchlhk@126.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300308
      • Tianjin Cancer Hospital Airport Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 75 years at the time of signing the informed consent form, regardless of gender;
• Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary tract cancers (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer);
• Have received first-line PD-1/PD-L1 inhibitor combined with chemotherapy and have experienced disease progression during or after systemic therapy;
• TROP2 immunohistochemistry score of 2+ or 3+;
• At least one measurable lesion per RECIST v1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to dosing;
• Life expectancy ≥ 12 weeks;

• Adequate organ and bone marrow function (without blood transfusion, recombinant human thrombopoietin, or colony-stimulating factor treatment within 2 weeks prior to dosing), defined as follows:

  1. Hematology: absolute neutrophil count (NEUT#) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin ≥ 90 g/L;
  2. Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for subjects with baseline liver metastases, ALT and AST ≤ 5 × ULN; albumin ≥ 30 g/L; total bilirubin (TBIL) ≤ 1.5 × ULN;
  3. Renal function: creatinine clearance ≥ 50 mL/min (calculated using the standard Cockcroft-Gault formula);
  4. Coagulation function: international normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) ≤ 1.5 × ULN;
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use effective medical contraceptive measures from the signing of the informed consent form through 6 months after the last dose ;
• Subjects voluntarily participate in this study, sign the informed consent form, and are able to comply with protocol-specified visits and related procedures.

Exclusion Criteria:

• Prior receipt of any of the following treatments (including in the adjuvant/neoadjuvant setting):

  1. TROP2-targeted therapy;
  2. Any drug targeting topoisomerase I, including antibody-drug conjugate (ADC) therapy;
• Use of strong inhibitors or inducers of cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks prior to the first dose or during the study period (use of strong CYP3A4 inhibitors or inducers is not permitted in this study; representative drugs are listed in Appendix 7); all subjects must avoid concomitant use of any known CYP3A4-inducing drugs, herbal supplements, and/or consumption of such foods;
• Documented history of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease that impairs/delays corneal healing;
• History of or current central nervous system (CNS) metastases;
• Other malignancy within 3 years prior to dosing (except for tumors cured by local therapy, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, etc.);

• Presence of any of the following cardiovascular or cerebrovascular diseases or risk factors:

  1. Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, Grade 3 or 4 heart failure (per New York Heart Association [NYHA] classification), symptomatic or poorly controlled severe arrhythmias, cerebrovascular accident, transient ischemic attack, or other serious cardiovascular or cerebrovascular diseases within 6 months prior to dosing;
  2. History of myocarditis, primary cardiomyopathy, specific cardiomyopathy, or other myocardial diseases;
  3. Any deep vein thrombosis (subjects may be enrolled if stable on low-molecular-weight heparin or similar therapeutic agents for ≥ 2 weeks), peripheral arterial thromboembolic events, pulmonary embolism, or other serious thromboembolic events within 3 months prior to dosing;
  4. Aortic aneurysm, aortic dissecting aneurysm, or other major vascular diseases that may be life-threatening or require surgery within 6 months prior to dosing;

• Uncontrolled systemic diseases per investigator judgment:

  1. Poorly controlled diabetes (fasting blood glucose ≥ 10 mmol/L on two consecutive occasions);
  2. Poorly controlled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg);
  3. Clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage (> 1 time/week);
• History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, current ILD or non-infectious pneumonitis, or suspected ILD or non-infectious pneumonitis that cannot be ruled out by imaging at screening;
• Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcers, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding;
• Toxicity from prior anti-tumor therapy has not recovered to ≤ Grade 1 (per NCI CTCAE v5.0) or to the levels specified in the eligibility criteria (excluding toxicities deemed by the investigator to have low safety risk, such as alopecia and fatigue);
• Active autoimmune disease requiring systemic treatment within the past 2 years, including disease-modifying antirheumatic drugs, immunosuppressants, or systemic corticosteroids (> 10 mg/day prednisone or equivalent). Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic therapy; subjects receiving systemic corticosteroids > 10 mg/day prednisone or other immunosuppressive agents within 2 weeks prior to dosing;
• Known active pulmonary tuberculosis. Subjects with suspected active pulmonary tuberculosis must undergo clinical examination to rule it out;
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Active hepatitis B [hepatitis B surface antigen (HBsAg)-positive, with HBV-DNA ≥ 500 IU/mL or above the lower limit of detection, whichever is higher] or active hepatitis C (hepatitis C antibody-positive with HCV-RNA above the lower limit of detection). Note: HBsAg-positive subjects are required to receive anti-HBV therapy during the study treatment period;
• Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
• Known allergy to the study drug or any of its components, or history of severe hypersensitivity reactions to other biological agents;
• Major surgery within 4 weeks prior to dosing, or expected to require major surgery during the study period;
• Severe infection within 4 weeks prior to dosing, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks prior to dosing;
• Receipt of non-specific immunomodulatory therapy (including but not limited to interferon, IL-2) or proprietary Chinese medicine preparations approved for anti-tumor indications within 2 weeks prior to dosing;
• Vaccination with live vaccine within 30 days prior to dosing, or planned vaccination with live vaccine during the study period;
• Rapid deterioration of disease during the screening period prior to dosing, such as significant changes in performance status;
• Pregnant or breastfeeding women;
• Local or systemic diseases unrelated to malignancy, or diseases or symptoms secondary to tumor, that may confer high medical risk and/or uncertainty in survival assessment, such as leukemoid reaction, cachexia, etc.;
• Any condition that, in the investigator's opinion, would interfere with the evaluation of the study drug, subject safety, or interpretation of study results, or any other condition deemed by the investigator as inappropriate for participation in this study.

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: Sacituzumab tirumotecan combined with envafolimab; Sacituzumab tirumotecan 5 mg/kg, administered intravenously (IV) on Day 1 of each cycle (d1), Q2W, for 3 cycles. Envafolimab 300 mg, administered subcutaneously (SC) on Day 1 of each cycle (d1), Q2W, for 3 cycles. Subsequent treatment decisions will be made by the investigator based on comprehensive efficacy assessments.	Drug: Sacituzumab tirumotecan combined with envafolimab; Sacituzumab tirumotecan 5 mg/kg, administered intravenously (IV) on Day 1 of each cycle (d1), Q2W, for 3 cycles. Envafolimab 300 mg, administered subcutaneously (SC) on Day 1 of each cycle (d1), Q2W, for 3 cycles. Subsequent treatment decisions will be made by the investigator based on comprehensive efficacy assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate (ORR) of sacituzumab tirumotecan combined with envafolimab in TROP2-positive advanced biliary tract cancers previously treated with first-line immunotherapy combined with chemotherapy, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival (OS) of sacituzumab tirumotecan combined with envafolimab in TROP2-positive advanced biliary tract cancers previously treated with first-line immunotherapy combined with chemotherapy;	3 years
PFS	Progression-free survival (PFS) of sacituzumab tirumotecan combined with envafolimab in TROP2-positive advanced biliary tract cancers previously treated with first-line immunotherapy combined with chemotherapy, as assessed by the investigator per RECIST v1.1	2 years
DCR	Disease control rate (DCR) of sacituzumab tirumotecan combined with envafolimab in TROP2-positive advanced biliary tract cancers previously treated with first-line immunotherapy combined with chemotherapy, as assessed by the investigator per RECIST v1.1;	1 year
DOR	Duration of response (DOR) of sacituzumab tirumotecan combined with envafolimab in TROP2-positive advanced biliary tract cancers previously treated with first-line immunotherapy combined with chemotherapy, as assessed by the investigator per RECIST v1.1;	2 years
Safety	The incidence and severity of adverse events (evaluated according to NCI CTCAE v5.0)	3 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; TROP2; antibody-drug conjugate; Biliary Tract Cancers
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms; envafolimab
• Other Study ID Numbers: SKB264-NSIP-028

Drug and device information, study documents

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