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

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU); Drug: Investigator's choice of SOC; Drug: SYS6010+SG001

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.

• Study Type: Interventional
• Enrollment (Estimated): 737
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 0311-69085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be able to understand and voluntarily sign the written ICF;
2. Age 18-75 (inclusive) years, male or female;
3. 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;
4. Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1;
5. Life expectancy ≥ 3 months;

Exclusion Criteria:

1. Prior treatment involving topoisomerase I inhibitors (including ADC drugs that contain topoisomerase I inhibitors as toxins);
2. 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)
3. 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;
4. With dihydropyrimidine dehydrogenase (DPD) deficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase II (Safety lead-in stage) : SYS6010+SG001+physician's choice(Capecitabine or 5-FU )	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.; Other Names: SG001: Enlonstobart
Experimental: 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.	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.; Other Names: SG001: Enlonstobart
Experimental: Phase II(randomized Controlled stage): SYS6010+SG001+ physician's choice (Capecitabine or 5-FU)	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.; Other Names: SG001: Enlonstobart
Active Comparator: PhaseII(randomized treatment stage): physician's choice of SOC	Drug: Investigator's choice of SOC; Camrelizumab + Cisplatin + Paclitaxel; Tislelizumab + Cisplatin + Paclitaxel; Tislelizumab + Cisplatin + 5-FU/Capecitabine
Experimental: Phase II(randomized controlled stage): SYS6010+SG001	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.
Active Comparator: Phase III: SYS6010+SG001+ physician's choice (Capecitabine or 5-FU)	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.; Other Names: SG001: Enlonstobart
Active Comparator: Phase III: physician's choice of SOC	Drug: Investigator's choice of SOC; Camrelizumab + Cisplatin + Paclitaxel; Tislelizumab + Cisplatin + Paclitaxel; Tislelizumab + Cisplatin + 5-FU/Capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PhaseII(safety leadrun-in stage): DLT; Description: Dose-limiting toxicity	Dose-limiting toxicity	28 days
PhaseII(safety run-inlead-in stage): AE	The incidence and severity of Adverse events	From the signing of the informed consent form until 90 days after the last dose.
PhaseII(safety leadrun-in stage): MTD;	Maximum tolerated dose	After phase II saftysafety run-inlead-in stage and dose expansion stage. Approximately 4 months.
PhaseII(safety run-inlead-in stage): RP2D	Recommended Phase II dose	After phase II saftysafety run-inlead-in stage and dose expansion stage. Approximately 4 months.
PhaseII(Randomized treatment stage): ORR per RECIST v1.1	Objective response rate	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	PFS assessed by independent review committee	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;	Overall survival	Through study completion, up to approximately 5 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: DOR per RECIST 1.1;	Duration of response.	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;	Disease of controll	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	Progression free survival	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	Overall survival	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	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;	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;	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.	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;	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	Duration of response assessed by independent review committee	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;	Disease of controll assessed by independent review committee.	Weeks 8, 12, 18, every 6 weeks within 48 weeks, and every 12
Phase III:PFS per RECIST 1.1;	Progression free survival	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;	Objective response rate assessed by independent review committee	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;	Incidence and severity of adverse events	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;	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	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	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 .	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	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

Collaborators and Investigators

• Sponsor: CSPC Megalith Biopharmaceutical Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2025
• Primary Completion (Estimated): December 30, 2029
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Capecitabine; Fluorouracil
• Other Study ID Numbers: SYS6010-016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No