A randomized, double-blind, phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for metastatic HER2+ breast cancer (HER2CLIMB-05) - HER2CLIMB-05

Seagen Inc.0 个研究点目标入组 650 人开始时间: 2022年12月5日最近更新: 2024年4月29日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Seagen Inc.
入组人数: 650

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional

入排标准

性别: All

入选标准

•1. Have centrally confirmed HER2+ breast carcinoma per 2018 American Society of Clinical Oncologists (ASCO)-College of American Pathologists (CAP) guidelines.
•2. Have unresectable locally advanced or metastatic (hereafter referred to as advanced”) disease; if recurrent (after [neo]adjuvant therapy), there must be a minimum 6-month treatment-free interval from any trastuzumab or pertuzumab received in the early breast cancer setting to the diagnosis of advanced HER2+ disease. Prior standard of care therapy for early breast cancer is permitted (eg, prior T-DM1); however, Exclusion Criterion 1 should be noted.
•3. Have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression (per investigator judgement)
•a. Subjects receiving <6 cycles (ie, 4-5 cycles) of taxane are only eligible if the taxane was stopped early due to intolerable toxicity (eg, documented neuropathy impacting function).
•b. Subjects are permitted to receive trastuzumab and pertuzumab for 1 additional cycle (after completion of chemotherapy) during screening to allow completion of screening procedures. Study treatment should begin within 6 weeks (± 3 days) from the start of the last cycle of trastuzumab and pertuzumab.
•c. Subjects newly found to have asymptomatic brain metastasis during screening and treated with local CNS-directed therapy are permitted to receive trastuzumab and pertuzumab for up to 2 additional cycles (after completion of chemotherapy) to allow for the mandatory washout period. Study treatment should begin within 9 weeks (± 3 days) from the start of the last cycle of trastuzumab and pertuzumab.
•4. Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-])
•5. Be at least 18 years of age, and legally an adult at time of consent and = the age of majority per regional requirements
•6. Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
•7. Have adequate hepatic function as defined in the protocol
•8. Have adequate baseline hematologic parameters as defined in the protocol
•9. Have a serum or plasma creatinine =1.5 X institutional ULN.
•10. Have left ventricular ejection fraction (LVEF) =50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment.
•11. Subjects of childbearing potential must meet the conditions as per protocol
•12. Male subjects must meet the conditions as per protocol
•13. Provide signed informed consent per a consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC) prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the subject’s disease
•14. Be willing and able to comply with study procedures
•15. CNS Inclusion – Based on screening contrast brain magnetic resonance imaging (MRI), subjects may have any of the following:
•a. No evidence of brain metastases
•b. Untreated brain metastases which are asymptomatic and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane
•c. Previously treated brain metastases which are asymptomatic
•i. Brain metastases previously treated with local therapy must not have progressed since treatment
•a. Time since whole brain r

排除标准

•1. Have previously been treated with any anti-HER2 and/or anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and at least 12 months have elapsed from the last neratinib dose to the start of study drug) or are currently participating in another interventional clinical trial
•2. Unable for any reason to undergo contrast MRI of the brain
•3. History of allergic reactions to trastuzumab, pertuzumab, or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion-related reactions (IRRs) to trastuzumab that were successfully managed, known allergy to one of the excipients in the study drugs, or hypersensitivity to murine proteins
•4. Are positive for Hepatitis B by surface antigen expression, positive for Hepatitis C infection, or the presence of known chronic liver disease. Subjects who have been treated for Hepatitis C infection are permitted if they have documented sustained virologic response of at least 12 weeks. The latest local guidelines should be followed regarding the testing of Hepatitis B DNA levels by polymerase chain reaction (PCR). Subjects with Hepatitis B DNA levels by PCR that require nucleoside analogue or other therapies are not eligible for the trial.
•5. Subjects known to be positive for human immunodeficiency virus (HIV) are excluded if they meet any of the following criteria:
•a. CD4+ T-cell count of <350 cells/µL
•b. Detectable HIV viral load
•c. History of an opportunistic infection within the past 12 months
•d. On stable antiretroviral therapy for <4 weeks
•6. Are pregnant, breastfeeding, or planning a pregnancy from time of informed consent until 7 months after the final dose of study drug
•7. Have inability to swallow pills or have significant GI disease or surgery which would preclude the adequate oral absorption of medications
•8. Have used a strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment
•9. Have current conditions of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled hypertension, or cardiac arrhythmia or history of myocardial infarction within 6 months prior to randomization
•10. Have any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
•11. Have evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment
•12. Have ongoing = Grade 2 toxicity from first-line induction therapy (ie, trastuzumab, pertuzumab, and taxane) with the exceptions of alopecia, neuropathy, and nail toxicity
•13. Have ongoing = Grade 2 diarrhea
•14. CNS Exclusion – Based on screening brain MRI and clinical assessment, subjects must not have any of the following:
•a. Symptomatic brain metastasis
•b. Progression of brain metastases since starting first-line trastuzumab, pertuzumab, and taxane
•c. Ongoing use of systemic corticosteroids at a total daily dose of >2 mg of dexamethasone (or equivalent). For subjects requiring systemic steroids for control of comorbidities (eg, asthma or autoimmune diseases), daily dose must not exceed 2 mg dexamethasone (or equivalent).
•d. Any untreated brain lesion in an anatomic site which may pose risk to subject (eg, brain stem lesions). Subjects who successfully undergo l

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发起方

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