A Clinical Study of SYS6023 Combination Therapy for Advanced Breast Cancer

NCT07597629 | Not Yet Recruiting Phase 2

• 1 other identifier: SYS6023-002
• Study Type: interventional
• Target: 114
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, multicenter Phase II clinical study conducted in subjects with advanced breast cancer.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (4)

• The incidence of dose-limiting toxicity (DLT)

  At the end of Cycle 1 (each cycle is 21 days).

• Frequency and severity of AEs and SAEs (according to NCI-CTCAE 6.0);

  Baseline up to 28 days post last dose, Up to approximately 3 years

• Recommended Phase 2 Dose（RP2D）

  Up to approximately 3 years

• Objective Response Rate (ORR)

  Up to approximately 3 years

Secondary Outcomes (11)

• Maximum Plasma Concentration( Cmax)

  Up to approximately 3 years

• Time to Maximum Plasma Concentration (Tmax)

  Up to approximately 3 years

• Area Under the Serum Concentration Time Curve ( AUC)

  Up to approximately 3 years

• Elimination half-life (t1/2)

  Up to approximately 3 years

• Anti-Drug Antibody（ADA）

  Up to approximately 3 years

Study Arms (3)

Cohort 1-Group A

EXPERIMENTAL

Patients with advanced breast cancer receiving SYS6023 in combination with HB1901 treatment.

Drug: SYS6023; Drug: HB1901

Cohort 1-Group B

EXPERIMENTAL

Patients with advanced breast cancer receiving SYS6023 treatment.

Drug: SYS6023

Cohort 2

EXPERIMENTAL

Patients with advanced breast cancer receiving SYS6023 in combination with KN026 treatment.

Drug: SYS6023; Drug: KN026

Interventions

SYS6023 DRUG

SYS6023 is a novel antibody-drug conjugate (ADC) targeting HER3, administered via intravenous infusion.

Cohort 1-Group A; Cohort 1-Group B; Cohort 2

HB1901 DRUG

HB1901 is a specific mTOR inhibitor, administered via intravenous infusion.

Cohort 1-Group A

KN026 DRUG

KN026 is an antibody targeting HER2, administered via intravenous infusion.

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥ 18 years old;
• \. Histologically or cytologically confirmed unresectable locally advanced or metastatic breast cancer:
• \. Sufficient tumor specimens must be provided for biomarker testing (human epidermal growth factor receptor 3-HER3), preferably obtained during or after the most recent treatment period; During safety run-in period, subjects who cannot provide sufficient tissue samples may be screened after sponsor's evaluation and approval;
• \. Documented disease progression or intolerability with the most recent systemic anti-tumor treatment;
• \. According to RECIST 1.1, at least one evaluable lesion (safety run-in period) or measurable lesion (cohort expansion phase);
• \. ECOG PS score 0-1;
• \. Expected survival ≥ 3 months;
• \. Adequate organ function with laboratory tests meeting criteria (no blood transfusion or hematopoietic growth factor therapy within 14 days before testing): ANC ≥ 1.5 × 10\^9/L PLT ≥ 100 × 10\^9/L Hb ≥ 90 g/L TBIL ≤ 1.5 × ULN ALT, AST ≤ 2.5 × ULN; for participants with liver metastasis, ALT and AST ≤ 5 × ULN Creatinine clearance rate (Ccr) \> 35 mL/min (calculated according to Cockcroft-Gault formula) Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; International normalized ratio (INR) ≤ 1.5 × ULN Left ventricular ejection fraction (LVEF) ≥ 55% (only applicable to Cohort 2)
• \. Eligible individuals with reproductive potential must agree to use reliable contraceptive methods (hormonal contraceptives, barrier methods, or abstinence) with their partners during the trial and for at least 7 months after the last dose; Women of childbearing potential must have a negative blood pregnancy test within 7 days before enrollment;
• \. Fully understand this clinical trial and voluntarily sign the written informed consent form.

You may not qualify if:

• \. Prior treatment with HER3-targeted ADC therapy;
• \. Applicable to Cohort 1: a. Prior treatment with any topoisomerase I inhibitor-loaded ADC therapy; b. Current presence or impending visceral crisis that has caused or may cause impending organ damage and/or other life-threatening complications;
• \. Applicable to Cohort 2: a. Prior exposure to anthracyclines with cumulative dose exceeding 360 mg/m\^2doxorubicin equivalent; b. LVEF once dropped to \< 40% during prior anti-HER2 drug therapy, or symptomatic CHF occurred;
• \. History of other malignancies within 3 years before randomization/first dose or concurrent active malignancies (except cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, etc., which are allowed to enroll);
• \. Untreated (including those detected during screening period) or unstable brain parenchymal metastasis, spinal cord metastasis or compression, carcinomatous meningitis. Subjects with treated stable brain metastases may be considered for enrollment (Note: refers to participants who have received local brain treatment, whose symptoms are stable, imaging tests show stability for at least 28 days before randomization/first dose, no evidence of progressive brain edema, and no need for glucocorticoids or other symptom control measures);
• \. Adverse reactions from prior anti-tumor therapy have not recovered to CTCAE 6.0 grade ≤ 1 (except for toxicities such as alopecia that researchers judge to have no safety risk);
• \. Major surgery within 28 days before randomization/first dose, or planned to undergo systemic or local tumor resection during the study period;
• \. History of severe bleeding risk (e.g., gastrointestinal varices) or bleeding diathesis, any gastrointestinal bleeding or other bleeding of ≥ CTCAE grade 2 within 28 days before randomization/first dose; Abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months before randomization/first dose;
• \. History of severe cardiovascular disease, including but not limited to:
• Acute coronary syndrome within 6 months before randomization/first dose;
• Stroke or transient ischemic attack within 6 months before randomization/first dose;
• Pulmonary embolism or deep vein thrombosis within 3 months before randomization/first dose (intermuscular vein thrombosis may be enrolled if assessed as low risk by researchers);
• CHF with NYHA functional classification ≥ II;
• Documented history of cardiomyopathy that has not currently recovered;
• Pericarditis;

Sponsors & Collaborators

• CSPC Megalith Biopharmaceutical Co.,Ltd.: lead

Central Study Contacts

Clinical Trials Information Group officer

CONTACT

86-0311-69085587; ctr-contact@cspc.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Arm 1 and Arm 2 are randomized controlled, receiving SYS6023 alone or SYS6023 in combination with HB1901, respectively; Arm 3 is a single-arm design, receiving SYS6023 in combination with KN026.

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): May 30, 2029
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share