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

Phase 3Not Yet RecruitingNCT07251062

CSPC Megalith Biopharmaceutical Co.,Ltd.737 enrolled

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

737

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

SYS6010+SG001+ physician's choice (Capecitabine or 5-FU)DRUG

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.

Investigator's choice of SOCDRUG

1. Camrelizumab + Cisplatin + Paclitaxel 2. Tislelizumab + Cisplatin + Paclitaxel 3. Tislelizumab + Cisplatin + 5-FU/Capecitabine

SYS6010+SG001DRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

PhaseII(safety leadrun-in stage): DLT; Description: Dose-limiting toxicity

Dose-limiting toxicity

Time frame: 28 days

PhaseII(safety run-inlead-in stage): AE

The incidence and severity of Adverse events

Time frame: From the signing of the informed consent form until 90 days after the last dose.

PhaseII(safety leadrun-in stage): MTD;

Maximum tolerated dose

Time frame: 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

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

Objective response rate

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

PFS assessed by independent review committee

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;

Overall survival

Time frame: Through study completion, up to approximately 5 year.

Secondary Outcomes

Central Contacts

Clinical Trials Information Group officer

CONTACT

0311-69085587 ctr-contact@cspc.cn

Data from ClinicalTrials.gov

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Phase II: DOR per RECIST 1.1;

Duration of response.

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;

Disease of controll

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

Progression free survival

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

Overall survival

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

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;

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;

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.

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;

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

Duration of response assessed by independent review committee

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;

Disease of controll assessed by independent review committee.

Time frame: Weeks 8, 12, 18, every 6 weeks within 48 weeks, and every 12

Phase III:PFS per RECIST 1.1;

Progression free survival

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 III:ORR-IRC;

Objective response rate assessed by independent review committee

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 III: AE;

Incidence and severity of adverse events

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: From first dose of treatment to 30 days after the last dose of treatment