A Phase 2 Open-label, Single Arm Study of MK-7119 in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic HER2+ Breast Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 66
- 试验地点
- 51
- 主要终点
- Confirmed Objective Response Rate(cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Determined by Independent Central Review (ICR): Japanese Participants
研究概览
简要总结
The goal of this study is to evaluate the efficacy and safety of tucatinib in combination with trastuzumab and capecitabine in participants with unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with taxane anti-cancer agent, trastuzumab, pertuzumab and trastuzumab emtansine (T-DM1). The primary hypothesis is that the confirmed objective response rate (cORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by independent central review (ICR) for the combination of tucatinib, trastuzumab and capecitabine, is greater than 20%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has histologically confirmed HER2+ breast carcinoma
- •Has received previous treatment with taxane anti-cancer agent, trastuzumab, pertuzumab, and T-DM1 with the exception of when the use of taxanes is contraindicated or judged not to be the best treatment at the investigator's discretion
- •Has radiographically and/or histologically confirmed disease progression on last systemic anticancer treatment
- •Has adequate organ function
- •Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP and using contraception or abstinent from heterosexual intercourse during the intervention period and for at least 30 days after receiving the last dose of tucatinib, 80 days after receiving the last dose of trastuzumab, or 180 days after receiving the last dose of capecitabine, whichever occurs last and agrees to not donate eggs during this period
- •Male participants refrain from donating sperm and are either abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after receiving the last dose of tucatinib and 90 days after receiving the last dose of capecitabine, whichever occurs last
- •Previously treated brain metastasis is stable or progressed, provided there is no clinical indication for immediate re-treatment
排除标准
- •Has been previously treated with lapatinib within 12 months of starting study treatment
- •Has been previously treated with neratinib, afatinib, tucatinib or capecitabine
- •Has a history of exposure to doxorubicin, epirubicin, mitoxantrone, idarubicin, liposomal doxorubicin
- •Has had treatment with any systemic anti-cancer therapy including hormonal therapy, non-central nervous system (CNS) radiation or experimental agent ≤3 weeks before first dose of study treatment
- •Has any toxicity related to prior cancer therapies that has not resolved with the exception of alopecia, congestive heart failure, anemia
- •Has clinically significant cardiopulmonary disease
- •Has known myocardial infarction or unstable angina within 6 months prior to the first dose of study treatment
- •Has any uncontrolled viral, bacterial or fungal infection within 14 days prior to the first dose of study treatment
- •Is positive for Hepatitis B, Hepatitis C or has known chronic liver disease
- •Is known to be positive for human immunodeficiency virus (HIV)
- •Has evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment
- •Has ongoing use of systemic corticosteroids for control of symptoms of brain metastases
- •Has any brain lesion thought to require immediate local therapy
- •Has known or suspected leptomeningeal disease (LMD)
- •Has poorly controlled generalized or complex partial seizures or manifest neurologic progression due to brain metastases
研究组 & 干预措施
Tucatinib + Trastuzumab + Capecitabine
Participants will receive tucatinib plus trastuzumab plus capecitabine. Tucatinib 300 mg will be administered orally twice daily (BID). Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose thereafter, will be administered intravenously (IV) on Day 1 of each 21-day cycle. Capecitabine 1000 mg/m^2 will be administered orally BID on Days 1-14 of each 21-day cycle. Tucatinib, trastuzumab and capecitabine treatment will continue until unacceptable toxicity, disease progression, death, withdrawal of consent or study closure.
干预措施: Tucatinib (Drug)
Tucatinib + Trastuzumab + Capecitabine
Participants will receive tucatinib plus trastuzumab plus capecitabine. Tucatinib 300 mg will be administered orally twice daily (BID). Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose thereafter, will be administered intravenously (IV) on Day 1 of each 21-day cycle. Capecitabine 1000 mg/m^2 will be administered orally BID on Days 1-14 of each 21-day cycle. Tucatinib, trastuzumab and capecitabine treatment will continue until unacceptable toxicity, disease progression, death, withdrawal of consent or study closure.
干预措施: Trastuzumab (Biological)
Tucatinib + Trastuzumab + Capecitabine
Participants will receive tucatinib plus trastuzumab plus capecitabine. Tucatinib 300 mg will be administered orally twice daily (BID). Trastuzumab 8 mg/kg loading dose followed by 6 mg/kg maintenance dose thereafter, will be administered intravenously (IV) on Day 1 of each 21-day cycle. Capecitabine 1000 mg/m^2 will be administered orally BID on Days 1-14 of each 21-day cycle. Tucatinib, trastuzumab and capecitabine treatment will continue until unacceptable toxicity, disease progression, death, withdrawal of consent or study closure.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Confirmed Objective Response Rate(cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Determined by Independent Central Review (ICR): Japanese Participants
时间窗: From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first (maximum up to 17.8 months)
cORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR), per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have a reduction in short axis to \<10 millimeter(mm). PR: a \>=30% decrease in the sum of diameters of target lesions, taking as a reference the baseline sum diameters. Only response assessments before first documented progressive disease(PD) or new anti-cancer therapies were considered. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study(included baseline sum if smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions was also considered PD. Participants with missing data were considered non-responders. cORR was determined by ICR. Two-sided 90% exact confidence interval was based on Clopper-Pearson method.
次要结局
- Duration of Response (DOR) Per RECIST Version 1.1 Determined by ICR: All Participants(From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first)
- Overall Survival: All Participants(From start of study treatment to date of death from any cause or censoring date)
- Number of Participants With Adverse Events, Serious Adverse Events and Treatment Related Adverse Events and Serious Adverse Events: All Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)
- Number of Participants With Dose Modifications and Treatment Discontinuations: Japanese Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)
- Number of Participants With Clinically Significant Changes in Vital Signs: Japanese Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)
- Duration of Response (DOR) Per RECIST Version 1.1 Determined by ICR: Japanese Participants(From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first)
- Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by INV: Japanese Participants(From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date)
- Number of Participants With Abnormalities in Laboratory Parameters: Japanese Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)
- Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by ICR: All Participants(From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first)
- Duration of Response (DOR) Per RECIST Version 1.1 Determined by INV: All Participants(From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first)
- Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by Investigator Assessment (INV): Japanese Participants(From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first)
- Confirmed Objective Response Rate(cORR) Per RECIST Version 1.1 Determined by INV: All Participants(From date of first dose until first documented disease progression or start of new anticancer therapy, whichever occurred first)
- Duration of Response (DOR) Per RECIST Version 1.1 Determined by INV: Japanese Participants(From date of first objective response (CR or PR that is subsequently confirmed) to documented PD, or death from any cause whichever occurred first)
- Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by ICR: All Participants(From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date)
- Number of Participants With Adverse Events, Serious Adverse Events and Treatment Related Adverse Events and Serious Adverse Events: Japanese Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)
- Number of Participants With Dose Modifications and Treatment Discontinuations: All Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)
- Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by ICR: Japanese Participants(From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date)
- Progression Free Survival (PFS) Per RECIST Version 1.1 Determined by INV: All Participants(From date of first dose to the date of documented disease progression or death from any cause whichever occurred first or censoring date)
- Overall Survival: Japanese Participants(From start of study treatment to date of death from any cause or censoring date)
- Number of Participants With Abnormalities in Laboratory Parameters: All Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)
- Number of Participants With Clinically Significant Changes in Vital Signs: All Participants(From date of first dose of study treatment to up to 30 days after last dose of study treatment)