An Open-label, Multicenter, Phase 2 Dose Optimization and Expansion Study to Evaluate the Safety and Efficacy of BB-1701, an Anti-human Epidermal Growth Factor Receptor 2 (Anti-HER2) Antibody-drug Conjugate (ADC), in Previously Treated Subjects With HER2-positive or HER2-low Unresectable or Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 56
- 试验地点
- 49
- 主要终点
- Part 1, Dose Optimization: Number of Participants With Clinically Significant 12-lead ECGs Values
研究概览
简要总结
The primary purpose of the Dose Optimization (Part 1) of this study is to assess the safety and tolerability of BB-1701 and to determine the recommended dose (RD) of BB-1701 for Dose Expansion (Part 2). The primary purpose of Dose Expansion (Part 2) is to assess the antitumor activity of BB-1701 at RD in the selected population(s) of breast cancer (BC).
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged >=18 years at the time of informed consent.
- •Metastatic or unresectable BC that is histologically confirmed to be either HER2-positive (defined as an immunohistochemistry [IHC] status of 3+, or a positive in situ hybridization [ISH] test [fluorescence, chromogenic, or silver-enhanced ISH] if IHC status is 2+) or HER2-low (defined as an IHC status of 1+, or 2+ and negative ISH) per the American Society of Clinical Oncology/College of American Pathology guidelines as documented prior to trastuzumab deruxtecan (T-DXd) treatment.
- •Must have previously received T-DXd.
- •Sufficient tumor tissue is required for HER2 status testing at a central laboratory.
- •Measurable disease per RECIST 1.1 as assessed by the investigator. Participants with bone only disease may be eligible if there is a measurable soft tissue component associated with the bone lesion.
- •Must have previously received at least 1 but no more than 3 prior chemotherapy-based regimes in the unresectable or metastatic setting. If recurrence occurred during or within 6 months of (neo) adjuvant chemotherapy, this would count as 1 line of chemotherapy.
- •If HR-positive HER2-low BC, must have previously received endocrine therapy and is not expected to further benefit from it.
- •ECOG PS 0 or
- •Life expectancy of at least 3 months.
- •Adequate organ function and laboratory parameters.
排除标准
- •Presence of brain or subdural metastases, unless participant has completed local therapy and has discontinued the use of corticosteroids for this indication for at least 2 weeks prior to starting treatment in this study.
- •Diagnosed with meningeal carcinomatosis.
- •Received anticancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, etc) or an investigational drug or device within the past 28 days or 5 half-lives, whichever is shorter.
- •Prior treatment with eribulin.
- •Any prior allergic reactions of Grade >=3 to monoclonal antibodies or contraindication to the receipt of corticosteroids or any of the excipients (investigators should refer to the prescribing information for the selected corticosteroid).
- •Residual toxic effects of prior therapies or surgical procedures that is Grade >=2 (except alopecia or anemia).
- •Grade >=2 peripheral neuropathy or history of Grade >=3 peripheral neuropathy or discontinued any prior treatment due to peripheral neuropathy.
- •Active pneumonitis/interstitial lung disease (ILD) or any clinically significant lung disease (example, chronic obstructive pulmonary disease), history of Grade >=2 pneumonitis/ILD, or received radiotherapy to lung fields within 12 months of Cycle 1 Day 1 of study treatment.
- •Congestive heart failure greater than (>) New York Heart Association Class II or left ventricular ejection fraction (LVEF) less than (<) 50 percent (%) measured by multigated acquisition scan (MUGA) or echocardiogram.
- •Has a corrected QT interval prolongation per Fridericia formula (QTcF) >470 millisecond (ms) (for both males and females) based on screening triplicate 12-lead ECG.
- •Concomitant active infection requiring systemic treatment, except:
- •If known to be human immunodeficiency virus (HIV)-positive, must be on anti-HIV therapy for at least 4 weeks and have a clusters of differentiation 4+ T-cell (CD4+) count >=350 cells per microliter (cells/mcL) and an HIV viral load <400 copies per milliliter (copies/mL).
- •If meets the criteria for anti-hepatitis B virus (HBV) therapy, must agree to take anti-HBV therapy, if known to be HBV-positive as defined by positive hepatitis B surface antigen or hepatitis B core antibody. HBV viral load must be undetectable.
- •If known to be hepatitis C virus (HCV)-positive must have completed curative therapy for HCV. HCV viral load must be undetectable.
- •Known history of active bacillus tuberculosis (TB).
- •Any medical or other condition which, in the opinion of the investigator would preclude the participant's participation in the clinical study.
研究组 & 干预措施
Part 1, Dose Optimization, Cohort 1
HER2-positive or HER2-low, unresectable or metastatic BC.
干预措施: BB-1701 (Drug)
Part 1, Dose Optimization, Cohort 2
HER2-positive or HER2-low, unresectable or metastatic BC.
干预措施: BB-1701 (Drug)
Part 1, Dose Optimization, Cohort 3
HER2-positive or HER2-low, unresectable or metastatic BC.
干预措施: BB-1701 (Drug)
Part 2, Dose Expansion
HER2-positive or HER2-low, unresectable or metastatic BC.
干预措施: BB-1701 (Drug)
结局指标
主要结局
Part 1, Dose Optimization: Number of Participants With Clinically Significant 12-lead ECGs Values
时间窗: Baseline up to 35 months
Number of participants with clinically significant 12-lead ECGs values will be reported.
Part 1, Dose Optimization: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
时间窗: Baseline up to 35 months
Number of participants with ECOG PS will be reported.
Part 1, Dose Optimization: Number of Participants With Adverse Events (AEs)
时间窗: Baseline up to 35 months
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product; Any new disease or exacerbation of an existing disease; any deterioration in non-protocol-required measurements of a laboratory value or other clinical test (example, electrocardiogram \[ECG\] or x-ray) that results in symptoms, a change in treatment, or discontinuation of study drug; Recurrence of an intermittent medical condition (example, headache) not present pretreatment (baseline); An abnormal laboratory test result should be considered an AE if the identified laboratory abnormality leads to any type of intervention, withdrawal of study drug, or withholding of study drug, whether prescribed in the protocol or not. An AE does not necessarily have a causal relationship with the medicinal product.
Part 1, Dose Optimization: Number of Participants With Clinically Significant Laboratory Values
时间窗: Baseline up to 35 months
Clinical laboratory parameters includes hematology, chemistry, and urinalysis.
Part 1, Dose Optimization: Number of Participants With Clinically Significant Vital Sign Values
时间窗: Baseline up to 35 months
Vital sign parameters includes systolic and diastolic blood pressure (BP), pulse, respiratory rate, body temperature.
Part 1, Dose Optimization: Objective Response Rate (ORR)
时间窗: From date of first dose of study drug until first documentation of CR or PR (up to 35 months)
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or confirmed partial response (PR) by investigator assessment per Response Evaluation Criteria for Solid Tumours (RECIST) version (v) 1.1.
Part 2, Dose Expansion: Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Assessment per RECIST v1.1
时间窗: From date of first dose of study drug until first documentation of CR or PR (up to 35 months)
ORR is defined as the percentage of participants achieving a confirmed CR or confirmed PR based on BICR assessment per RECIST v1.1.
次要结局
- Part 1, Dose Optimization: Overall Survival (OS)(From the date of first dose to the date of death (up to 35 months))
- Part 1, Dose Optimization: Duration of Response (DOR)(From the date of documented CR or PR to the date of PD or death, whichever occurs first (up to 35 months))
- Part 1, Dose Optimization: Disease Control Rate (DCR)(From the date of first dose until PD or death, whichever occurs first (up to 35 months))
- Part 1, Dose Optimization: Clinical Benefit Rate (CBR)(From the date of first dose until PD or death, whichever occurs first (up to 35 months))
- Part 1, Dose Optimization, Cmax: Maximum Observed Concentration of BB-1701, Total Antibody and Eribulin (Payload)(Baseline up to 35 months)
- Part 1, Dose Optimization, Tmax: Time to Reach Maximum Observed Concentration (Cmax) of BB-1701, Total Antibody and Eribulin (Payload)(Baseline up to 35 months)
- Part 1, Dose Optimization, AUC(0-inf): Area Under the Concentration-time Curve From Zero Time to Infinity of BB-1701, Total Antibody and Eribulin (Payload)(Baseline up to 35 months)
- Part 2, Dose Expansion: Number of Participants With Clinically Significant Laboratory Values(Baseline up to 35 months)
- Part 1, Dose Optimization: Time to Response (TTR)(From the date of first dose to the day of the first documented CR or PR (up to 35 months))
- Part 1, Dose Optimization, CL: Total Body Clearance of BB-1701(Baseline up to 35 months)
- Part 1, Dose Optimization: Statistical Correlation Between Serum Concentrations of BB-1701 with ORR and AEs(Baseline up to 35 months)
- Part 2, Dose Expansion: Duration of Response (DOR) Based on BICR Assessment by RECIST v1.1(From the date of documented CR or PR to the date of PD or death, whichever occurs first (up to 35 months))
- Part 2, Dose Expansion: Number of Participants With Clinically Significant Vital Sign Values(Baseline up to 35 months)
- Part 2, Dose Expansion: Number of Participants With Clinically Significant 12-lead ECGs Values(Baseline up to 35 months)
- Part 1, Dose Optimization: Progression-free Survival (PFS)(From the date of first dose to the date of the first documentation of PD or death, whichever occurs first (up to 35 months))
- Part 1, Dose Optimization, AUC(0-t): Area Under the Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration of BB-1701, Total Antibody and Eribulin (Payload)(Baseline up to 35 months)
- Part 2, Dose Expansion: Clinical Benefit Rate (CBR) Based on BICR Assessment per RECIST v1.1(From the date of first dose until PD or death, whichever occurs first (up to 35 months))
- Part 2, Dose Expansion: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)(Baseline up to 35 months)
- Part 1, Dose Optimization, t1/2: Terminal Phase Elimination Half-life of BB-1701(Baseline up to 35 months)
- Part 1, Dose Optimization, Vss: Volume of Distribution at Steady State for BB-1701(Baseline up to 35 months)
- Part 1, Dose Optimization, Ctrough: Trough Concentration of BB-1701(Baseline up to 35 months)
- Part 2, Dose Expansion: Disease Control Rate (DCR) Based on BICR Assessment per RECIST v1.1(From the date of first dose until first documentation of CR or PR or SD (up to 35 months))
- Part 2, Dose Expansion: Overall Survival (OS)(From the date of first dose to the date of death (up to 35 months))
- Part 2, Dose Expansion: Number of Participants With AEs(Baseline up to 35 months)
- Part 2, Dose Expansion: Time to Response (TTR) Based on BICR Assessment per RECIST v1.1(From the date of first dose to the day of the first documented CR or PR (up to 35 months))
- Part 2, Dose Expansion: Progression-free Survival (PFS) Based on BICR Assessment per RECIST v1.1(From the date of first dose to the date of the first documentation of PD or death, whichever occurs first (up to 35 months))