Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB-02)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 466
- 试验地点
- 866
- 主要终点
- Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment
研究概览
简要总结
This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery.
Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer.
Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.
详细描述
This study is designed to evaluate the efficacy and safety of tucatinib in combination with T-DM1 in participants with unresectable locally-advanced or metastatic HER2+ breast cancer who have had prior treatment with a taxane and trastuzumab in any setting. Prior pertuzumab treatment is permitted, but not required. Participants will be randomized in a 1:1 manner to receive 21-day cycles of either tucatinib or placebo in combination with T-DM1.
While on study treatment, participants will be assessed for progression every 6 weeks for the first 24 weeks, and every 9 weeks thereafter, irrespective of dose holds or interruptions. Study treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. After completion of study treatment and after occurrence of disease progression, participants in both arms of the study will continue to be followed for survival until study closure or withdrawal of consent.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria:
- •Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory
- •History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination
- •Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy
- •Measurable or non-measurable disease assessable by RECIST v1.1
- •ECOG performance status score of 0 or 1
- •CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must have at least one of the following:
- •(a) No evidence of brain metastases
- •(b) Untreated brain metastases not needing immediate local therapy
- •(c) Previously treated brain metastases
- •Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy
- •Participants treated with CNS local therapy for newly identified lesions or previously treated and progressing lesions may be eligible to enroll if all of the following criteria are met:
- •(i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 14 days prior to first dose, or time since surgical resection is at least 28 days.
- •(ii) Other sites of evaluable disease are present
- •Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
排除标准
- •Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity).
- •CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following:
- •Any untreated brain lesions >2 cm in size
- •Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).
- •Any brain lesion thought to require immediate local therapy
- •Known or concurrent leptomeningeal disease as documented by the investigator
- •Poorly controlled generalized or complex partial seizures
研究组 & 干预措施
Tucatinib + T-DM1
Tucatinib + T-DM1
干预措施: tucatinib (Drug)
Tucatinib + T-DM1
Tucatinib + T-DM1
干预措施: T-DM1 (Drug)
Placebo + T-DM1
Placebo + T-DM1
干预措施: placebo (Drug)
Placebo + T-DM1
Placebo + T-DM1
干预措施: T-DM1 (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment
时间窗: From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months)
PFS as per investigator was defined as the time from the date of randomization to the investigator assessment of disease progression (PD) as per RECIST v1.1 or death from any cause, whichever occurred first. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter (mm). Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment.
次要结局
- Overall Survival (OS)(Up to approximately 5 years)
- Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator Assessment(From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 45 months))
- Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator Assessment(From the date of first CR or PR until the date of the first documentation of PD or death, whichever occurred first (maximum up to 43 months))
- Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR)(From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months))
- Progression-Free Survival in Participants With Brain Metastases at Baseline as Per RECIST v1.1 Determined by BICR(From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months))
- Objective Response Rate as Per RECIST v1.1 Determined by BICR(From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months))
- Overall Survival in Participants With Brain Metastases at Baseline(Up to approximately 5 years)
- Duration of Response (DOR) as Per RECIST v1.1 Based on Investigator Assessment(Up to approximately 5 years)
- Duration of Response as Per RECIST v1.1 by BICR(Up to approximately 5 years)
- Clinical Benefit Rate (CBR) Per RECIST v1.1 Based on Investigator Assessment(Up to approximately 5 years)
- Clinical Benefit Rate as Per RECIST v1.1 by BICR(Up to approximately 5 years)
- Number of Participants With Treatment Emergent Adverse Events (AEs)(From start of treatment up to 30 days after the last study treatment (approximately 43 months))