Patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) that is deemed unresectable face a bleak prognosis. Recent phase 1/2 studies have demonstrated the efficacy and safety of augmenting neoadjuvant concurrent chemoradiotherapy with immunotherapy in treating resectable ESCC. The present study is a prospective, 3-arm, randomized trial that seeks to evaluate the efficacy of diverse conversion therapy modalities in patients with unresectable ESCC. The study objectives include R0 resection rate, treatment-related adverse events, morbidity and mortality, 1-year progression-free survival (PFS), and 1-year overall survival (OS) rates.
Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). Tislelizumab was specifically engineered to minimize binding to FcɤR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy.
This trial will provide valuable insights into the effectiveness of the three conversion therapy modalities and help to inform clinical decision-making for patients with unresectable locally advanced ESCC.
Histologically confirmed sorely ESCC without other histology subtypes.
Thoracic esophageal cancer.
No prior anti-cancer treatment, including but not limited to surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
Borderline unresectable locally advanced ESCC deemed by investigators as suspicious of but not confirmed T4b according to the American Joint Committee on Cancer (AJCC) 8th edition staging classification or extracapsular lymph node involvement (ELNI).
Synchronous and metachronous primary malignancies in but not limited to the upper aerodigestive tract, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.
Patients have undergone any type of anti-cancer treatment.
Baseline clinical stage M1 per AJCC 8th edition of staging classification, including supraclavicular lymph node metastases.
Investigators assessed major vessel involvement with high-risk hemorrhage.
Parallel
Tislelizumab (BGB-A317) with chemoradiotherapy
Combination productDifferent sequences and methods of treatment to convert surgery
R0 resection rate
Minimal distance tumor/circumferential resection margin (CRM) \> 1 mm.
1-year OS rate
Defined as the proportion of patients still alive within one year from treatment initiation.
1-year PFS
Defined as the proportion of patients without disease progression or death within one year from treatment initiation.
Positive rate of circulating tumor DNA (ctDNA) in minimal residual disease (MRD) before and after neoadjuvant treatment and its correlation with the pathological response and disease progression during surveilance
To investigate whether ctDNA variation can be used for MRD predicting incidence of pathological incidence and monitoring tumor progression after surgery
Incidence of Treatment-Emergent Adverse Events
Adverse event during chemoRT or immunotherapy
Click on the lead sponsor to view all of their trials.
