Breast Cancer, HER2-positive Breast Cancer
Conditions
Keywords
HER2-positive breast cancer, SHR-A1811
Brief summary
This is a prospective, multicenter, open-label, randomized, controlled Study. The purpose of this study is to evaluate the efficacy and safety of SHR-A1811 versus pyrotinib plus capecitabine in the treatment of trastuzumab primary-resistant HER2-positive advanced breast cancer.
Interventions
DRUGSHR-A1811
4.8 mg/kg administered as an intravenous infusion on Day 1 of each cycle. 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.
DRUGPyrotinib
400 mg, administered orally once daily, continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.
DRUGCapecitabine
1000mg/m2, administered orally twice daily on Days 1-14, with no administration on Days 15-21, 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.
DRUGT-DXd
5.4 mg/kg administered as an intravenous infusion on Day 1 of each cycle. 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.
Sponsors
Peking University Cancer Hospital & Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Histologically or cytologically confirmed HER2-positive advanced breast cancer (IHC 3+, or IHC 2+ with ISH amplification). 3. ECOG performance status 0-2. 4. Estimated life expectancy \>12 weeks. 5. At least one measurable lesion per RECIST v1.1 criteria; 6. Patients with trastuzumab primary resistance is defined as follows: 1. Progression during or within 12 months after treatment in neoadjuvant or adjuvant setting (at least 9 weeks of trastuzumab treatment); 2. For patients with de novo stage IV disease, progression during or within 3 months after treatment for locally advanced or metastatic disease in the first-line setting (at least 6 weeks of trastuzumab treatment). 7. Adequate organ function as defined by the following laboratory criteria: 1. Hematologic: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, hemoglobin (HGB) ≥90 g/L. 2. Hepatic: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) (≤5 × ULN in patients with liver metastases); total serum bilirubin (TBIL) ≤1.5 × ULN; serum albumin ≥30 g/L. 3. Renal: serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula. 4. Coagulation: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 × ULN. 5. Cardiac: left ventricular ejection fraction (LVEF) ≥50%. 8. Women of childbearing potential must have a negative pregnancy test at screening, and subjects of reproductive potential must agree to use effective contraception from study start until 6 months after the last dose of study treatment.. 9. Voluntary participation with written informed consent obtained prior to any study-related procedures.
Exclusion criteria
1. Prior or current exposure to antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, including but not limited to fam-trastuzumab deruxtecan (DS-8201a). 2. Active brain metastases or leptomeningeal metastases (patients with asymptomatic/inactive brain metastases are allowed to be enrolled); 3. Other malignancy diagnosed within 5 years prior to enrollment, excluding cured non-melanoma skin cancer, cervical carcinoma in situ, ductal carcinoma in situ, or stage I grade 1 endometrial cancer; 4. Radiotherapy, any anti-HER2 targeted therapy, or chemotherapy within 4 weeks prior to enrollment; endocrine therapy within 2 weeks prior to enrollment; 5. Positive for human immunodeficiency virus (HIV); 6. Known hypersensitivity to any study drug or its excipients, or to humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab, etc.); 7. Clinically significant cardiovascular disease, such as severe/unstable angina, symptomatic congestive heart failure (NYHA Class ≥II), clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, myocardial infarction within 6 months prior to first dose, or cerebrovascular accident (including transient ischemic attack). 8. Participants known or suspected to interstitial lung disease. 9. Concurrent participation in any other interventional drug clinical trial. 10. Refusal to comply with protocol-mandated follow-up. Presence of any additional severe physical or psychiatric disorder, or any laboratory abnormality that, in the investigator's judgment, could increase the subject's risk, confound study results, or render the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS during treatment phase 1 | Start of treatment until 2-year follow-up | progression free survival during treatment phase 1 : time from randomization to the first observation of tumor progression or death from any cause during treatment phase 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total PFS across treatment phase 1 and treatment phase 2 | Start of treatment until 3-year follow-up | Total progression free survival across treatment phase 1 and treatment phase 2: time from randomization to the second observation of tumor progression or death from any cause across treatment phase 1 and treatment phase 2. |
| PFS during treatment phase 2 | Start of treatment until 3-year follow-up | progression free survival during treatment phase 2 : time from the first observation of tumor progression to the second observation of tumor progression or death from any cause during treatment phase 2. |
| ORR during treatment phase 1 | Start of treatment until 2-year follow-up | Objective response rate during treatment phase 1: proportion of subjects who achieved complete response (CR) or partial response (PR) by primary tumor imaging evaluation during treatment phase 1. |
| DCR during treatment phase 1 | Start of treatment until 2-year follow-up | Disease control rate during treatment phase 1: proportion of subjects who achieved complete response (CR) or partial response (PR) or stable disease (SD) by primary tumor imaging evaluation during treatment phase 1. |
| OS | Start of treatment until 3-year follow-up | Overall survival: time from randomization to death from any cause. |
| Incidence of adverse events | Start of treatment until 3-year follow-up | — |
| Severity of adverse events | Start of treatment until 3-year follow-up | — |
| Incidence of serious adverse events | Start of treatment until 3-year follow-up | — |
| Severity of serious adverse events | Start of treatment until 3-year follow-up | — |
Contacts
CONTACTHanfang Jiang
PRINCIPAL_INVESTIGATORHanfang Jiang
Peking University Cancer Hospital & Institute
Outcome results
None listed