A Randomized, Double-Blind, Phase 3 Study Evaluating the Efficacy and Safety of ABP 980 Compared With Trastuzumab in Subjects With HER2 Positive Early Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 725
- 试验地点
- 1
- 主要终点
- Percentage of Participants With a Pathologic Complete Response
研究概览
简要总结
The purpose of this research study is to compare the effectiveness and safety of ABP 980 against trastuzumab in women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females ≥ 18 years of age
- •Histologically confirmed invasive breast cancer
- •Planning for surgical resection of breast tumor and sentinel node or axillary lymph node resection
- •Planning neoadjuvant chemotherapy
- •HER2 positive disease
- •Measurable disease in the breast after diagnostic biopsy, defined as longest diameter ≥ 2.0 cm
- •Known estrogen receptor (ER) and progesterone receptor (PR) hormone receptor status at study entry
- •Normal bone marrow function
- •Normal hepatic function
- •Normal renal function
- •Subjects must sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form before any study specific procedures
- •Inclusion Criteria for Randomization:
- •Left ventricular ejection fraction (LVEF) of ≥55% by 2D echocardiogram
- •Complete all 4 cycles of run-in chemotherapy
排除标准
- •Bilateral breast cancer
- •Presence of known metastases
- •Received prior treatment, including chemotherapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer
- •Other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
- •Pre-existing clinically significant (≥ grade 2) peripheral neuropathy
- •Any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current angina pectoris requiring a medicinal product, current clinically significant valvular disease, current evidence of transmural infarction on electrocardiogram (ECG), or current poorly controlled hypertension
- •Severe dyspnea at rest requiring supplementary oxygen therapy
- •History of positivity for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV)
- •Recent infection requiring a course of systemic anti-infectives that were completed ≤ 14 days before enrollment (with the exception of uncomplicated urinary tract infection)
- •Woman of childbearing potential who is pregnant or is breast feeding
- •Woman of childbearing potential who is not consenting to use highly effective methods of birth control (eg, true abstinence [periodic abstinence (eg calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception], sterilization, or other non-hormonal forms of contraception) during treatment and for at least 7 months after the last administration of the protocol specified treatment
- •Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study
- •Other investigational procedures while participating in this study are excluded
- •Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, murine proteins, or to any of the excipients
- •Subject previously has enrolled and/or has been randomized in this study
- •Subject likely to not be available to complete all protocol required study visits or procedures
- •History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
研究组 & 干预措施
ABP 980
Participants received ABP 980 at an initial dose of 8 mg/kg by intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.
Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.
After surgery (adjuvant phase) participants continued receiving 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.
干预措施: ABP 980 (Drug)
ABP 980
Participants received ABP 980 at an initial dose of 8 mg/kg by intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.
Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.
After surgery (adjuvant phase) participants continued receiving 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.
干预措施: Paclitaxel (Drug)
ABP 980
Participants received ABP 980 at an initial dose of 8 mg/kg by intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.
Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.
After surgery (adjuvant phase) participants continued receiving 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.
干预措施: Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection (Procedure)
Trastuzumab
Participants received trastuzumab at an initial dose of 8 mg/kg IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.
Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.
After surgery (adjuvant phase) participants were re-randomized to either continue receiving 6 mg/kg trastuzumab IV Q3W or transition to 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.
干预措施: Trastuzumab (Drug)
Trastuzumab
Participants received trastuzumab at an initial dose of 8 mg/kg IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.
Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.
After surgery (adjuvant phase) participants were re-randomized to either continue receiving 6 mg/kg trastuzumab IV Q3W or transition to 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.
干预措施: Paclitaxel (Drug)
Trastuzumab
Participants received trastuzumab at an initial dose of 8 mg/kg IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.
Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.
After surgery (adjuvant phase) participants were re-randomized to either continue receiving 6 mg/kg trastuzumab IV Q3W or transition to 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.
干预措施: Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection (Procedure)
结局指标
主要结局
Percentage of Participants With a Pathologic Complete Response
时间窗: 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase
Pathologic complete response (pCR) was defined as the absence of invasive tumor cells in the breast tissue and in axillary lymph nodes, regardless of residual ductal carcinoma in situ (DCIS). Participants underwent a lumpectomy or mastectomy with sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND) within 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase. The pathology evaluation of surgical specimens for pCR analysis was conducted by local laboratories at the study sites.
次要结局
- Percentage of Participants With a Pathologic Complete Response in Breast Tissue Only(3 to 7 weeks after the last dose of study drug in the neoadjuvant phase)
- Percentage of Participants With a Pathologic Complete Response in Breast Tissue and Axillary Lymph Nodes and Absence of DCIS(3 to 7 weeks after the last dose of study drug in the neoadjuvant phase)