Esophageal cancer
Conditions
Interventions
Experimental group:Anlotinib hydrochloride plus bemipalimab
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Histologically or cytologically confirmed unresectable locally advanced, recurrent, or metastatic esophageal squamous-cell carcinoma (mixed adenosquamous carcinomas excluded). 2.No prior systemic therapy for advanced disease, OR recurrence/progression >= 6 months after completion of neoadjuvant/adjuvant therapy or definitive chemoradiation. 3.Age >= 18 years at informed-consent signature; ECOG performance status 0–1; expected survival > 3 months. 4.Tumor tissue demonstrates TP53 or FAT1 mutation and absence of NOTCH3 mutation. 5.At least one measurable lesion per RECIST 1.1 that has not received prior local therapy (lesions within a prior irradiation field may qualify if documented progression). 6.Adequate organ function within 14 days before enrollment: (1)Hemoglobin >= 90 g/L; (2)Absolute neutrophil count >= 1.5 × 10^9/L; (3)Platelet count >= 75 × 10^9/L; (4)Total bilirubin = 60 mL/min; (7)PT, aPTT, INR <= 1.5 × ULN (no anticoagulant therapy); (8)TSH <= ULN; if abnormal, T3 and T4 must be normal. 7.Women of child-bearing potential: negative serum/urine pregnancy test within 7 days before enrollment and agreement to use highly effective contraception from screening through 6 months after last dose. Men: agreement to use condoms plus contraception for partner (if applicable) through 6 months after last dose. 8.Signed written informed consent; willing and able to comply with study procedures.
Exclusion criteria
Exclusion criteria: 1.Any other malignancy within 3 years before first dose, except: single-surgery cure with >=5 years disease-free survival; cured cervical carcinoma in-situ, non-melanoma skin cancer, or superficial bladder tumors [Ta, Tis, T1]. 2.Conditions preventing i.v. access or oral drug intake (e.g., dysphagia, chronic diarrhea, bowel obstruction). 3.Prior therapy toxicities not resolved to = 3 in the National Surgical Classification Catalogue (2022 edition). 5.Active bleeding esophageal tumor within 2 months, or any of the following within 3 months: hematemesis/melena >= 2.5 mL/day, >= CTCAE grade 3 bleeding event, or any bleeding history/tendency deemed high-risk by the investigator. 6.Arterial or venous thrombo-embolic event within 6 months (e.g., stroke, TIA, DVT, PE). 7.Uncontrolled viral hepatitis: (1)HBsAg+ requires HBV DNA >= 2000 IU/mL (or 1 × 10^4 copies/mL) and no >= 1-week suppressive therapy or = II heart failure or LVEF 450 ms (men) or > 470 ms (women) (average of 3 triplicate ECGs); (6)Congenital long-QT syndrome (personal/family); (7)Deep-vein thrombosis, PE, or other severe thrombo-embolism within 3 months (port/catheter or superficial vein thrombosis excluded); (8)Aspirin > 325 mg/day or anti-platelet agents (dipyridamole, ticlopidine, clopidogrel, cilostazol) within 7 days. 14.Active or uncontrolled infection >= CTCAE grade 2. 15.Renal failure requiring hemo- or peritoneal dialysis. 16.Immunodeficiency (including HIV-positive) or congenital acquired immune deficiency. 17.Systemic immunosuppressive therapy (including absorbable local steroids) within 7 days before first dose, except daily prednisone equivalent <= 10 mg. 18.Epilepsy requiring treatment. 19.Tumour-related issues: (1)Chemotherapy/immunotherapy <= 3 weeks, radiotherapy <= 2 weeks, small-molecule targeted therapy <= 5 half-lives (whichever shorter) before first dose; target lesion within prior RT field must have progressed; (2)Chinese proprietary anti-cancer agents with labelled oncologic indications within 2 weeks; (3)Imaging evidence of tumour invading adjacent organs (aorta/trachea) with high fistula/bleeding risk, or ulcerative ESCC adjacent to major vessels; (4)Near-complete luminal obstruction requiring endoscopic intervent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival;Investigator-assessed progression-free survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Biomarker;Investigator-assessed objective response rate (ORR);safety;Investigator-assessed duration of response (DOR);Investigator-assessed disease control rate (DCR); | — |
Countries
China
Contacts
Public ContactWang Feng
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed