Advanced/metastatic esophageal squamous cell carcinoma
Conditions
Interventions
II-SYS6010+SG001+Calcium Folinate +5-FU:II-SYS6010+SG001+Calcium Folinate +5-FU
II-SYS6010+SG001+Capecitabine :II-SYS6010+SG001+Capecitabine
II-Camrelizumab+Cisplatin+Paclitaxel:II-Camrelizumab+Cisplatin+Paclitaxel
II-Tislelizumab+Cisplatin+Paclitaxel:II-Tislelizumab+Cisplatin+Paclitaxel
II-Tislelizumab+Cisplatin+5-FU:II-Tislelizumab+Cisplatin+5-FU
II-Tislelizumab+Cisplatin+Capecitabine:II-Tislelizumab+Cisplatin+Capecitabine
II-SYS6010+SG001:II-SYS6010+SG001
III-SYS6010+SG001+Calcium Folinate +5-FU:III-SYS6010+SG001+Calcium Folinate +5-FU
III-SYS6010+SG001+Capecitabine:III-SYS6010+SG001+Capecitabine
III-Camrelizumab+Cisplatin+Paclitaxel:III-Camrelizumab+Cisplatin+Paclitaxel
III-Tislelizumab+Cisplatin+Paclitaxel:III-Tislelizumab+Cisplatin+Paclitaxel
III-Tislelizumab+Cisplatin+5-FU:III-Tislelizumab+Cisplatin+5-FU
III-Tislelizumab+Cisplatin+Capecitabine:III-Tislelizumab+Cisplatin+Capecitabine
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for inclusion in this study: 1. Aged between 18 and 75 years (inclusive), regardless of gender. 2. Histologically or cytologically confirmed esophageal squamous cell carcinoma , which is locally advanced unresectable or metastatic. No prior systemic anti-tumor therapy for the recurrent/metastatic stage is allowed. 3. At least one measurable lesion that meets the requirements of the Response Evaluation Criteria in Solid Tumors (RECIST V1.1). (This may not be required in the safety run-in phase.) 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 5. Life expectancy of >= 3 months. 6. Adequate organ function, as defined by the following criteria, within 7 days prior to the first dose of the study drug:Hematological (No blood transfusion, G-CSF, TPO, interleukin-11, or EPO within 2 weeks prior to the first dose): Absolute neutrophil count (ANC) >=1.5 × 10^9/L; Platelets >=100 × 10^9/L; Hemoglobin (Hb) >=90 g/L.Renal: Serum creatinine = 60 mL/min (calculated using the Cockcroft-Gault formula). Hepatic: Total bilirubin 1.5 is acceptable if the investigator deems the subject to be clinically stable and without bleeding risk. 7. Subjects must agree to use highly effective contraception from the time of signing the informed consent form until 6 months after the last dose of study drug. During this period, female subjects must not be breastfeeding, and male subjects must refrain from sperm donation. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of the study drug. 8. Voluntary participation in this clinical study, understanding of the study procedures, and ability to provide written informed consent.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be excluded from the study: 1. Patients with active central nervous system metastases, leptomeningeal metastases, or spinal cord compression. Patients with previously treated brain metastases may be considered for enrollment if they have stable lesions (i.e., no evidence of disease progression) confirmed by two consecutive imaging examinations (interval >=4 weeks), have stable clinical symptoms, and have not required steroid treatment for at least 2 weeks prior to the first dose of the study drug. 2. History of gastrointestinal perforation and/or fistula within 6 months prior to administration, or tumor invasion of adjacent organs at the esophageal disease site (e.g., mediastinum, aorta, or respiratory tract, etc.), which in the investigator's assessment increases the risk of fistula formation. 3. Patients with tracheal stent implantation or esophageal stent implantation for any reason, except for stent implantation due to benign stenotic scarring. 4. Poorly controlled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (recurrence with clinical significance requiring additional intervention within 2 weeks prior to enrollment). 5. History of other malignancies within 3 years prior to the first administration of the investigational drug, except for the following cases: cured basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the prostate, papillary thyroid carcinoma, and cervical carcinoma in situ, etc. 6. Prior treatment containing topoisomerase I inhibitors (including ADC). 7. History of Grade >=3 allergic reactions to monoclonal antibodies, or known allergy or intolerance to SYS6010, SG001, paclitaxel, carboplatin, cisplatin, fluorouracil, or their excipients. 8. Patients with known dihydropyrimidine dehydrogenase deficiency (DPD deficiency). 9. Adverse events from prior anti-tumor therapy have not recovered to CTCAE V5.0 Grade = 450 ms for males, >= 470 ms for females (Fridericia's formula: QTcF = QT/RR0.33, RR = 60/heart rate); (2)Acute coronary syndrome, acute myocardial infarction, unstable angina, heart failure, coronary artery bypass graft surgery, or stroke within 6 months prior to the first dose of the study drug; (3)Heart failure with New York Heart Association (NYHA) Class II
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) .;Adverse Events (AEs);Determination of the Maximum Tolerated Dose (MTD), if applicable.;Recommended Phase II Dose (RP2D).;(Randomized Controlled Phase): Investigator-Assessed Objective Response Rate (ORR).;Independent Review Committee (IRC)-Assessed Progression-Free Survival (PFS).;Overall Survival (OS).; | — |
Secondary
| Measure | Time frame |
|---|---|
| Effectiveness indicators:Efficacy Endpoints: Duration of Response (DoR), Disease Control Rate (DCR), Progression-Free Survival (PFS), Overall Survival (OS), among others;Pharmacokinetics (PK):Serum concentrations of toxin-bound antibody, total antibody, and JS-1 following single and multiple doses of SYS6010.Serum concentrations following single and multiple doses of SG001.;Immunogenicity:Incidence and titer of anti-drug antibodies (ADA) against SYS6010 and SG001. ? Incidence of neutralizing antibodies (NAb), if applicable.;Biomarkers: EGFR protein expression and PD-L1 protein expression.;Investigator-Assessed Progression-Free Survival (PFS).;Objective Response Rate (ORR), Duration of Response (DoR), and Disease Control Rate (DCR) as assessed by both the Independent Review Committee (IRC) and the Investigator.;The Incidence and Severity of Adverse Events; | — |
Countries
China
Contacts
Public ContactRuihua Xu
Sun Yat-sen University Cancer Center
Outcome results
None listed