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
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- CSPC Megalith Biopharmaceutical Co.,Ltd.
- Enrollment
- 400
- Primary Endpoint
- PFS
Overview
Brief Summary
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).
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18 to 75 years inclusive, no gender restrictions.
- •Histopathologically confirmed breast cancer at an unresectable recurrent or metastatic stage, requiring: a) HER2-negative; b) EGFR-positive expression.
- •Subjects must have received 1 to 2 lines of systemic chemotherapy regimens during the unresectable advanced or metastatic stage.
- •At least one measurable lesion confirmed by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Brain metastases are evaluated only as non-target lesions. Patients with skin lesions only are ineligible.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Expected survival ≥3 months.
- •Adequate major organ function status within 7 days prior to first study drug administration.
- •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.
- •Voluntarily participate in this clinical study, understand the research procedures, and be able to sign a written informed consent form.
Exclusion Criteria
- •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.
- •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).
- •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
- •Prior treatment with topoisomerase I inhibitors (including ADCs)
- •Prior treatment with EGFR-targeted ADCs or monoclonal antibodies
- •Known hypersensitivity to any component of SYS6010 or to humanized monoclonal antibody products
- •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).
- •Patients with inadequate washout periods for prior medications or treatments, as specified in the protocol, prior to the first administration of the study drug.
- •History of severe cardiovascular or cerebrovascular disease.
- •10\. Clinically significant pulmonary impairment due to pulmonary complications.
Arms & Interventions
SYS6010
Intervention: SYS6010 (Drug)
Investigator's Choice of Chemotherapy
eribulin, capecitabine, gemcitabine, or vinorelbine
Intervention: Investigator's Choice of Chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) (Drug)
Outcomes
Primary Outcomes
PFS
Time Frame: Randomization up to approximately 36 months
PFS(progression free survival) assessed by BICR based on RECIST v1.1 criteria
Secondary Outcomes
- OS (overall survival)(Randomization up to approximately 60 months)
- Progression-Free Survival (PFS) Assessed by Investigator(Randomization up to approximately 36 months)
- Objective Response Rate (ORR)(Randomization up to approximately 36 months.)
- Disease Control Rate (DCR)(Randomization up to approximately 36 months.)
- Duration of Response (DoR)(Randomization up to approximately 36 months)
- Mean change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Randomization up to approximately 36 months)
- Mean change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer Module 42 (EORTC QLQ-BR42)(Randomization up to approximately 36 months)
- AEs and SAEs(From first dose of study treatment until 30 days after the last dose.)
- Maximum Observed Plasma Concentration (Cmax) of SYS6010(Up to approximately 168 hours after the first dose of SYS6010.)
- Area Under the Plasma Concentration-Time Curve (AUC) of SYS6010(From the first dose up to approximately 168 hours post-dose.)
- Number of Participants With Anti-Drug Antibodies (ADAs) to SYS6010(From baseline (prior to first dose) up to approximately 30 days after the last dose of SYS6010.)