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.
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+;
TROP2-targeted therapy;
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;