A Phase III Study of SYS6010 Versus Chemotherapy in HER2-Negative, EGFR-Positive Recurrent or Metastatic Breast Cancer

A Randomized, Open-Label, Parallel-Control, Multicenter Phase III Clinical Study of SYS6010 Versus Investigator's Choice Chemotherapy in HER2-Negative, EGFR-Positive Recurrent or Metastatic Breast Cancer

This study is a multicenter, randomized, open-label, parallel-control Phase III clinical trial enrolling patients with unresectable HER2-negative, EGFR-positive recurrent/metastatic breast cancer who have previously failed first- or second-line chemotherapy. It aims to compare the efficacy and safety of SYS6010 monotherapy versus investigator-selected chemotherapy.The study plans to enroll approximately 400 subjects, randomly assigned in a 1:1 ratio to the treatment arm and control arm(Investigator's choice of standard chemotherapy regimen, including eribulin, capecitabine, gemcitabine, or vinorelbine).

This is a randomized, open-label, multicenter study designed to evaluate the efficacy and safety of SYS6010 injection versus investigator's choice of standard chemotherapy in patients with unresectable locally advanced or metastatic breast cancer that is HER2-negative with centrally confirmed EGFR expression, who have received at least one but no more than two prior lines of systemic chemotherapy for advanced or metastatic disease.

Approximately 400 patients will be enrolled and randomized in a 1:1 ratio to receive either SYS6010 injection or investigator's choice of chemotherapy. Patients randomized to the experimental arm will receive SYS6010 injection。 Patients randomized to the control arm will receive investigator's choice of standard chemotherapy, which may include eribulin, capecitabine, gemcitabine, or vinorelbine, administered per local label and institutional standard practice.

This study aims to determine whether SYS6010 provides clinically meaningful improvement in PFS compared with standard chemotherapy in patients with HER2-negative, EGFR-expressing advanced breast cancer.

The primary endpoint is progression-free survival (PFS) assessed by a blinded independent central review (BICR) per RECIST v1.1.

Secondary endpoints include overall survival (OS), investigator-assessed PFS, objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR), safety and tolerability, quality of life, pharmacokinetics, and immunogenicity.

Inclusion Criteria:

1. Age 18 to 75 years inclusive, no gender restrictions.
2. Histopathologically confirmed breast cancer at an unresectable recurrent or metastatic stage, requiring: a) HER2-negative; b) EGFR-positive expression.
3. Subjects must have received 1 to 2 lines of systemic chemotherapy regimens during the unresectable advanced or metastatic stage.
4. At least one measurable lesion confirmed by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Brain metastases are evaluated only as non-target lesions. Patients with skin lesions only are ineligible.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
6. Expected survival ≥3 months.
7. Adequate major organ function status within 7 days prior to first study drug administration.
8. Subjects must agree to use effective contraception from informed consent signing until the protocol-specified time after last dose; females must not be lactating and males must refrain from sperm donation during this period. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first study drug administration. Female subjects must not be lactating.
9. Voluntarily participate in this clinical study, understand the research procedures, and be able to sign a written informed consent form.

Exclusion Criteria:

1. Presence of cancerous meningitis, spinal cord compression, or active central nervous system metastases. Active central nervous system metastases are specifically defined as untreated, symptomatic, or requiring corticosteroids/anticonvulsants to control related symptoms; except for cases stable for at least one month following treatment for brain metastases and having discontinued corticosteroids/anticonvulsants for >2 weeks.
2. Poorly controlled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (including clinically significant recurrence requiring additional intervention within 2 weeks prior to enrollment).
3. History of other malignancies within 3 years prior to first use of study drug, except for: cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate carcinoma in situ, papillary thyroid carcinoma, and cervical carcinoma in situ
4. Prior treatment with topoisomerase I inhibitors (including ADCs)
5. Prior treatment with EGFR-targeted ADCs or monoclonal antibodies
6. Known hypersensitivity to any component of SYS6010 or to humanized monoclonal antibody products
7. Adverse events from prior antitumor therapy not recovered to ≤ Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 (excluding Grade 2 alopecia, asymptomatic laboratory abnormalities, etc., deemed safe by the investigator).
8. Patients with inadequate washout periods for prior medications or treatments, as specified in the protocol, prior to the first administration of the study drug. 9. History of severe cardiovascular or cerebrovascular disease.

10. Clinically significant pulmonary impairment due to pulmonary complications. 11. History of interstitial lung disease (ILD)/non-infectious pneumonia requiring glucocorticoid therapy, current ILD/non-infectious pneumonia, or inability to exclude ILD/non-infectious pneumonia based on imaging at screening.

12. Subjects with active inflammatory bowel disease, gastrointestinal obstruction, active peptic ulcer, recent (within 4 weeks) gastrointestinal bleeding, gastrointestinal perforation, or severe gastrointestinal conditions such as abdominal abscess (excluding those with a history of resolved conditions).

13. Severe infection within 4 weeks prior to first use of the investigational drug, including but not limited to: bacteremia requiring hospitalization, severe pneumonia, active tuberculosis infection, or requiring oral or intravenous antibiotic, antifungal, or antiviral therapy due to infection within 2 weeks prior to first dosing (except for prophylactic use).

14. Uncontrolled diabetes (fasting blood glucose ≥10 mmol/L and/or HbA1c ≥8%). 15. Active hepatitis B, active hepatitis C virus infection, or active syphilis infection.

16. Human immunodeficiency virus (HIV) infection diagnosed as acquired immunodeficiency syndrome (AIDS).

17.Other conditions deemed unsuitable for participation in this clinical trial by the investigator (e.g., uncontrolled psychiatric disorders or anticipated poor compliance).