Sequential Tegafur-gimeracil-oteracil Potassium Capsule (s-1) and Serplulimab Following Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Inoperable Esophageal Squamous Cell Carcinoma: A Single-Arm Phase II Clinical Trial
This Phase II trial evaluates the efficacy and safety of Serplulimab combined with S1 chemotherapy in patients with inoperable, locally advanced esophageal squamous cell carcinoma after concurrent chemoradiation. The primary endpoint is the one-year progression-free survival rate. Secondary measures include clinical response rates, overall survival, duration of response, and safety profiles. Exploratory goals focus on the potential of biomarkers like PD-L1 and ctDNA to predict treatment outcomes. Treatment involves initial chemoradiation followed by consolidation with Serplulimab and S1, continuing for up to 12 months or until disease progression or unacceptable toxicity.
• Able to understand and voluntarily sign a written informed consent form, which must be signed before initiating any study-specific procedures.
• Male or female participants aged between 18 and 70 years at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Histologically or cytologically confirmed diagnosis of locally advanced esophageal squamous cell carcinoma (ESCC); or patients who refuse surgery; staged as T1-4bN1-3M0 (according to AJCC 8th edition).
• Medically inoperable or refusal of surgery.
• No prior anti-tumor treatment.
• Expected survival of at least 6 months.
• At least one measurable lesion as defined by RECIST v1.1.
• Participants must provide either archived (within the last 2 years) or freshly obtained tumor tissue samples, with at least three unstained FFPE pathology slides.
• Adequate organ function defined as follows:
• a. Hematology (no blood transfusions or growth factor support within 7 days before starting study treatment): i. Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L (1500/mm³); ii. Platelet count ≥100×10\^9/L (100000/mm³); iii. Hemoglobin ≥90 g/L. b. Renal: i. Calculated creatinine clearance (CrCl) ≥50 mL/min using the Cockcroft-Gault formula: CrCl (mL/min) = {(140-age) × weight (kg) × F} / (SCr (mg/dL) × 72), where F=1 for males and 0.85 for females; SCr=serum creatinine.
⁃ ii. Urinary protein \<2+ or 24-hour urinary protein quantification \<1.0 g. c. Liver: i. Total bilirubin (TBiL) ≤1.5×ULN; ii. AST and ALT ≤2.5×ULN (≤5×ULN for participants with liver metastases); iii. Serum albumin (ALB) ≥28 g/L. d. Coagulation: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN, unless the participant is receiving anticoagulant therapy and INR and APTT are within the expected range of their therapeutic use.
⁃ e. Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥50%.
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study medication. If urine test is not conclusive, a serum test will be administered. If sexually active with a non-sterilized male partner, the participant must agree to use effective contraception during the study and for 120 days after the last dose of study medication. Discussion with the researcher is required regarding cessation of contraception after this point.
• Male participants with female partners of childbearing potential must agree to use effective contraception from screening to 120 days after the last dose of study medication. Discussion with the researcher is required regarding cessation of contraception after this point.
• Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.