Ivonescimab(AK112) Combined With Chemotherapy as the First-line Treatment in Patients With Advanced Esophageal Squamous Cell Carcinoma (ESCC): A Single Arm , Phase II Trial
This is a single arm，phase 2 study evaluating the safety and efficacy of Ivonescimab(AK112) combined with chemotherapy in the treatment of advanced esophageal squamous cell carcinoma (ESCC). In this study, patients with advanced esophageal squamous cell carcinoma who had not received any systematic treatment in the past will be enrolled. The research will be conducted in two stages. In the first part, 6 patients were enrolled in the group. After the last subject in the group completed at least 21 days of observation after the first medication, the researchers will conduct a preliminary safety and effectiveness assessment. If the safety and tolerability are good, it will enter the second expansion part till the study enrolled 30 patients. Patients who met the inclusion criteria were treated with AK112 (20mg/kg, intravenous infusion, d1, Q3W) in combination with albumin paclitaxel (220mg/m2, intravenous infusion, d1, Q3W) and cisplatin (75mg/m2, intravenous infusion, d1, Q3W), of which the maximum treatment time of chemotherapy was up to six cycles, and the maximum treatment time of AK112 was 24 months. Patients received regular and periodic reviews, with imaging evaluations every 6 weeks.
• Signed the informed consent；
• Male or female patients ≥18 and ≤ 75 years old;
• ECOG physical status score is 0 or 1;
• Patients with non resectable or metastatic advanced ESCC confirmed by pathological ocytological examination;
• No previous systemic treatment;
• Expected survival time ≥ 3 months;
• Patients must have at least one measurable metastatic lesion according to RECIST version 1.1;
• Normal organ function:
∙ Hematology :Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3); Platelet count ≥ 100 × 109/L (100000/mm3); Hemoglobin ≥ 90g/L;
‣ Kidney:The calculated value of creatinine clearance rate (CrCl) is ≥ 50 mL/min;Normal urine routine, urine protein\<2+or 24-hour (h) urine protein quantification\<1.0 g;
‣ Liver:Total serum bilirubin (TBiL) ≤ 1.5 × ULN;AST and ALT ≤ 2.5 × ULN; For subjects with liver metastasis, AST and ALT can be ≤ 5 × ULN;Serum albumin (ALB) ≥ 30g/L;
‣ Normal coagulation function, international standardized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
• Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; For males, surgical sterilization or agreement to use appropriate methods of contraception during observation and within 8 weeks after the last administration of study medication should be considered;
⁃ Comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study;