A Study of SYS6010, Enlonstobart, and Chemotherapy for First-Line Treatment of Esophageal Squamous Cell Carcinoma.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU), Investigator's choice of SOC, SYS6010+SG001.
- Who it may be relevant to
- Registry conditions: Esophageal Squamous Cell Carcinoma. Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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.
Overview
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.
Detailed description
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.
Interventions
- Drug SYS6010+SG001+ physician's choice (Capecitabine or 5-FU)
SYS6010 is an antibody conjugate drug (ADC), composed of one anti-EGFR monoclonal antibody coupled to one JS1 via an enzyme specific linker. SG001 is a recombinant, fully human, anti-PD-1 monoclonal antibody. Capecitabine: Capecitabine is for oral administration. 5-FU: Administration at the conventional dosage. - Drug Investigator's choice of SOC
1. Camrelizumab + Cisplatin + Paclitaxel 2. Tislelizumab + Cisplatin + Paclitaxel 3. Tislelizumab + Cisplatin + 5-FU/Capecitabine - Drug SYS6010+SG001
SYS6010 is an antibody conjugate drug (ADC), composed of one anti-EGFR monoclonal antibody coupled to one JS1 via an enzyme specific linker. SG001 is a recombinant, fully human, anti-PD-1 monoclonal antibody.
Primary outcome measures
- PhaseII(safety leadrun-in stage): DLT; Description: Dose-limiting toxicity [Time frame: 28 days]
- PhaseII(safety run-inlead-in stage): AE [Time frame: From the signing of the informed consent form until 90 days after the last dose.]
- PhaseII(safety leadrun-in stage): MTD; [Time frame: After phase II saftysafety run-inlead-in stage and dose expansion stage. Approximately 4 months.]
- PhaseII(safety run-inlead-in stage): RP2D [Time frame: After phase II saftysafety run-inlead-in stage and dose expansion stage. Approximately 4 months.]
- PhaseII(Randomized treatment stage): ORR per RECIST v1.1 [Time frame: 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.]
- PhaseIII: PFS-ICR [Time frame: 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]
- PhaseIII: OS; [Time frame: Through study completion, up to approximately 5 year.]
Secondary outcome measures (12)
- Phase II: DOR per RECIST 1.1; [Time frame: 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; [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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; [Time frame: From first dose of treatment to 30 days after the last dose of treatment.]
- Phase II: EGFR protein expression and PD-L1 protein expression; [Time frame: 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. [Time frame: 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; [Time frame: From first dose of treatment to 30 days after the last dose of treatment.]
- Phase III: DOR-IRC per RECIST 1.1 [Time frame: 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; [Time frame: Weeks 8, 12, 18, every 6 weeks within 48 weeks, and every 12]
- Phase III:PFS per RECIST 1.1; [Time frame: 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.]
Eligibility criteria
Inclusion criteria
- 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;
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Sequential
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT07251062 · SYS6010-016