A Study of SYS6010, Enlonstobart, and Chemotherapy for First-Line Treatment of Esophageal Squamous Cell Carcinoma.

Phase II study comprises a safety lead-in stage, a dose expansion stage, and a randomized treatment stage. The Phsae III study is randomized controlled trial.

Phase II (safety lead-in stage): the safety lead-in stage employs a 3+3 design. It aims to evaluate the safety and tolerability of combination therapy-comprising capecitabine/5-FU administered at a descending dose level starting from DL0 alongside fixed doses of SYS6010 and SG001-in previously untreated patients with unresectable locally advanced or metastatic ESCC. The primary objectives are to determine the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D).

Phase II (dose expansion stage): Upon completion of the safety evaluation and confirmation of tolerability for a dose cohort in the safety lead-in phase, expansion of that cohort may be initiated, with plans to expand 1-2 dose cohorts.

Phase II (randomized treatment stage): Upon determination of the RP2D based on prior data, a randomized controlled study will be conducted in a first-line advanced/metastatic esophageal squamous cell carcinoma (ESCC) patient population. Patients will be randomly assigned to three arms: Arm 1: SYS6010+SG001+ capecitabine/5-FU; arm2: investigator's choice of SOC; arm3: SYS6010+SG001.

Phase III is a randomized, controlled, open-label, multicenter study designed to evaluate the efficacy of SYS6010+SG001+capecitabine/5-FU versus investigator's choice of treatment as first-line therapy for advanced/metastatic esophageal squamous cell carcinoma. The Phase III trial design will be finalized based on Phase II results. The preliminary plan is to randomized patients in a 1:1 ratio to either the investigational arm or the control arm. Investigational arm: SYS6010+SG001+capecitabine/5-FU; control arm: investigator's choice of SOC.

• Phase II: DOR per RECIST 1.1; [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years]
• Phase II: DCR per RECIST 1.1; [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years]
• Phase II:PFS per RECIST 1.1 [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years]
• Phase II:OS [Срок оценки: Through study completion, up to approximately 5 year]
• Phase II: Serum concentrations of toxin-bound antibodies, total antibodies, and JS-1 following single and multiple doses of SYS6010 [Срок оценки: From first dose of treatment to 30 days after the last dose of treatment.]
• Phase II: plasma concentration of SG001 following single and multiple doses of SG001; [Срок оценки: From first dose of treatment to 30 days after the last dose of treatment.]
• Phase II: EGFR protein expression and PD-L1 protein expression; [Срок оценки: From first dose of treatment to 30 days after the last dose of treatment.]
• Phase II: The incidence and titer of anti-drug antibodies (ADA), as well as the incidence of neutralizing antibodies (NAb) (if applicable), for SYS6010. [Срок оценки: From first dose of treatment to 30 days after the last dose of treatment.]
• Phase II: The incidence and titer of anti-drug antibodies (ADA), as well as the incidence of neutralizing antibodies (NAb) (if applicable), for SG001; [Срок оценки: From first dose of treatment to 30 days after the last dose of treatment.]
• Phase III: DOR-IRC per RECIST 1.1 [Срок оценки: Weeks 8, 12, 18, every 6 weeks within 48 weeks, and every 12 weeks thereafter, until the end of the study]
• Phase III: DCR-IRC per RECIST 1.1; [Срок оценки: Weeks 8, 12, 18, every 6 weeks within 48 weeks, and every 12]
• Phase III:PFS per RECIST 1.1; [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.]