Breast Cancer, Triple Negative Breast Cancer (TNBC)
Conditions
Keywords
triple negative breast cancer
Brief summary
This study is a prospective, open-label, phase III, randomized controlled clinical trial. It is planned to screen patients with inoperable locally advanced or metastatic triple-negative breast cancer of the BLIS subtype. A total of 140 patients are planned to be enrolled.
Interventions
DRUGSHR- A1811
SHRA1811(HER-targeted ADC) 4.8 mg/kg, administered via intravenous infusion on Day 1 of each 3-week cycle.
DRUGSHR-A1811+BEV
SHRA1811(HER-targeted ADC) at 4.8 mg/kg in combination with BEV(bevacizumab) at 15 mg/kg, administered by intravenous infusion on Day 1, with a 3-week treatment cycle.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Female patients aged ≥18 years and ≤70 years; 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; 3. Life expectancy of at least 3 months; 4. Histologically confirmed invasive triple-negative breast cancer (defined as breast cancer with estrogen receptor \[ER\], progesterone receptor \[PR\], and human epidermal growth factor receptor 2 \[HER-2\] all determined to be negative by pathological testing. Specifically: ER-negative: IHC \<1%; PR-negative: IHC \<1%; HER2-negative: IHC -/+ or IHC ++ with FISH/CISH negative. All specimens must be verified as the BLIS subtype of the Fudan quadruple molecular classification by the Precision Medicine Center/Department of Pathology at the study's participating center); 5. Tumor stage: recurrent or metastatic breast cancer; for locally recurrent disease, radical surgical resection must be confirmed by the investigator to be not feasible. Number of prior lines of therapy in the advanced setting ≤2; 6. Patients must have at least one lesion (measurable and/or non-measurable) that has not been previously irradiated, can be accurately assessed at baseline by CT/MRI, and can be repeatedly evaluated according to RECIST 1.1; 7. Adequate major organ function, meeting the following criteria: Hematological parameters: hemoglobin (HB) ≥90 g/L (without blood transfusion within 14 days); absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count (PLT) ≥75×10⁹/L;Biochemical parameters: total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; in the presence of liver metastases, ALT and AST ≤5×ULN; serum creatinine (Cr) ≤1×ULN, and calculated creatinine clearance \>50 mL/min (Cockcroft-Gault formula); 8. No prior radiotherapy, endocrine therapy, molecular targeted therapy, or surgery within 3 weeks before study initiation, and recovery from acute toxicities of prior treatment (if surgery was performed, the wound must be completely healed); no peripheral neuropathy or only grade I peripheral neurotoxicity; 9. Female subjects of childbearing potential must agree to use a medically accepted contraceptive method during the study treatment period and for at least 3 months after the last dose of study drug; 10. Subjects must voluntarily participate in this study, sign the informed consent form, have good compliance, and be willing to cooperate with follow-up.
Exclusion criteria
* Patients with any of the following criteria will be excluded from this study: 1. Known central nervous system (CNS) metastases or a history of CNS metastases prior to screening. For patients with clinically suspected CNS metastases, contrast-enhanced CT or contrast-enhanced magnetic resonance imaging (MRI) must be performed within 28 days before the first dose to rule out CNS metastases; 2. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina pectoris, myocardial infarction within the past 6 months, or ventricular arrhythmias; 3. Persistent adverse events of Grade ≥1 resulting from prior treatment. Exceptions to this are alopecia or conditions that the investigator deems should not preclude enrollment. Such cases should be clearly documented in the investigator's notes; 4. Major surgery (excluding minor procedures such as placement of vascular access) within 3 weeks before the first cycle of study treatment; 5. Pregnant or lactating patients; 6. Other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin; 7. Presence of third-space fluid accumulation (e.g., massive pleural effusion or ascites) that cannot be controlled by drainage or other methods; 8. Participation in another anti-tumor drug clinical trial within 3 weeks before the first use of the study drug; 9. Long-term unhealed wounds or incompletely healed fractures; 10. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or HBV DNA ≥500 IU/mL, or chronic hepatitis with abnormal liver function; 11. History of allergic constitution, known allergy to any component of the study drug regimen, or history of allergy to other monoclonal antibodies; 12. History of gastrointestinal bleeding within the past 6 months, or clear evidence of a tendency for gastrointestinal bleeding, such as esophageal varices at risk of bleeding, active local ulcerative lesions, or fecal occult blood test ≥ (++). Patients with fecal occult blood test (+) should undergo gastroscopy; 13. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to study enrollment; 14. Urinalysis showing urine protein ≥ (++), or confirmed 24-hour urine protein quantification \>1.0 g; 15. Hypertension that cannot be controlled to within normal range with antihypertensive medication (systolic blood pressure \>140 mmHg, diastolic blood pressure \>90 mmHg); 16. Prior use of anti-angiogenic agents or prior exposure to an antibody-drug conjugate (ADC) with a topoisomerase I inhibitor as the payload
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival(PFS) | 24 months | Time to progressive disease (according to RECIST1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 24 months | Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions |
| Duration of Response (DoR) | 24 months | the time from the first documented objective response (complete response or partial response) to the first documented disease progression or death from any cause, whichever occurs first. |
| Disease Control Rate (DCR) | 24 months | The proportion of evaluable patients who achieve Complete Response (CR) , Partial Response (PR) , or Stable Disease (SD) after treatment. |
| Overall survival (OS) | 24months | Time from the enrollment to death of any cause |
| Safety and Tolerability | 24months | Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 5.0) Toxicity Reporting Criteria. |
Contacts
CONTACTZhimin Shao
CONTACTYin Liu
Outcome results
None listed