A Phase II/III Study to Evaluate the Efficacy and Safety of SYS6010 in Combination With SG001 With or Without 5-FU/Capecitabine in Subjects With First-Line Advanced/Metastatic Esophageal Squamous Cell Carcinoma.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 737
- 主要终点
- PhaseII(safety leadrun-in stage): DLT; Description: Dose-limiting toxicity
研究概览
简要总结
This is a multicenter phase 2/3 clinical study to evaluate the efficacy and safety of SYS6010 plus SG001±5-FU/Capecitabine as first-line treatment, in patients with advanced/metastatic esophageal squamous cell carcinoma.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be able to understand and voluntarily sign the written ICF;
- •Age 18-75 (inclusive) years, male or female;
- •With histologically/cytologically confirmed esophageal squamous cell carcinoma that is either locally advanced unresectable or metastatic, with no prior systemic antitumor therapy administered for the recurrent/metastatic disease setting. Have at least one measurable lesion that meets the RECIST v 1.1 criteria at baseline;
- •Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1;
- •Life expectancy ≥ 3 months;
排除标准
- •Prior treatment involving topoisomerase I inhibitors (including ADC drugs that contain topoisomerase I inhibitors as toxins);
- •Prior treatment with immune checkpoint inhibitors or other agents targeting T-cell co-stimulatory/co-inhibitory pathways (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137 antibodies)
- •With a history of ≥Grade 3 allergic reactions to monoclonal antibodies, or with known hypersensitivity or intolerance to SYS6010, SG001, paclitaxel, carboplatin, cisplatin, fluorouracil, or any of their excipients;
- •With dihydropyrimidine dehydrogenase (DPD) deficiency.
研究组 & 干预措施
Phase II (Safety lead-in stage) : SYS6010+SG001+physician's choice(Capecitabine or 5-FU )
干预措施: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU) (Drug)
Phase II (dose expansion stage): SYS6010+SG001+physician's choice (Capecitabine or 5-FU)
Upon completion of the safety evaluation and confirmation of tolerability for a dose cohort in the safety run-in phase, expansion of that cohort may be initiated, with plans to expand 1-2 dose cohorts.
干预措施: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU) (Drug)
Phase II(randomized Controlled stage): SYS6010+SG001+ physician's choice (Capecitabine or 5-FU)
干预措施: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU) (Drug)
PhaseII(randomized treatment stage): physician's choice of SOC
干预措施: Investigator's choice of SOC (Drug)
Phase II(randomized controlled stage): SYS6010+SG001
干预措施: SYS6010+SG001 (Drug)
Phase III: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU)
干预措施: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU) (Drug)
Phase III: physician's choice of SOC
干预措施: Investigator's choice of SOC (Drug)
结局指标
主要结局
PhaseII(safety leadrun-in stage): DLT; Description: Dose-limiting toxicity
时间窗: 28 days
Dose-limiting toxicity
PhaseII(safety run-inlead-in stage): AE
时间窗: From the signing of the informed consent form until 90 days after the last dose.
The incidence and severity of Adverse events
PhaseII(safety leadrun-in stage): MTD;
时间窗: After phase II saftysafety run-inlead-in stage and dose expansion stage. Approximately 4 months.
Maximum tolerated dose
PhaseII(safety run-inlead-in stage): RP2D
时间窗: After phase II saftysafety run-inlead-in stage and dose expansion stage. Approximately 4 months.
Recommended Phase II dose
PhaseIII: OS;
时间窗: Through study completion, up to approximately 5 year.
Overall survival
PhaseII(Randomized treatment stage): ORR per RECIST v1.1
时间窗: 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.
Objective response rate
PhaseIII: PFS-ICR
时间窗: 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
PFS assessed by independent review committee
次要结局
- Phase II: DOR per RECIST 1.1;(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;(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(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(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(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;(From first dose of treatment to 30 days after the last dose of treatment.)
- Phase II: EGFR protein expression and PD-L1 protein expression;(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.(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;(From first dose of treatment to 30 days after the last dose of treatment.)
- Phase III: DOR-IRC per RECIST 1.1(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;(Weeks 8, 12, 18, every 6 weeks within 48 weeks, and every 12)
- Phase III:PFS per RECIST 1.1;(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 III:ORR-IRC;(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 III: AE;(From first dose of treatment to 90 days after the last dose of treatment.)
- Phase III: Serum concentrations of toxin-bound antibodies, total antibodies, and JS-1 following single and multiple doses of SYS6010;(From first dose of treatment to 30 days after the last dose of treatment.)
- Phase III: plasma concentration of SG001 following single and multiple doses of SG001(From first dose of treatment to 30 days after the last dose of treatment.From first dose of treatment to 30 days after the last dose of treatment.)
- Phase III: EGFR protein expression and PD-L1 protein expression(From first dose of treatment to 30 days after the last dose of treatment.)
- Phase III: The incidence and titer of anti-drug antibodies (ADA), as well as the incidence of neutralizing antibodies (NAb) (if applicable), for SYS6010 .(From first dose of treatment to 30 days after the last dose of treatment.)
- The incidence and titer of anti-drug antibodies (ADA), as well as the incidence of neutralizing antibodies (NAb) (if applicable), for SG001(From first dose of treatment to 30 days after the last dose of treatment)