In two phase III clinical trials, EMILIA and TH3RESA, T-DM1 was shown to be effective in HER2-positive metastatic breast cancer patients who had progressed to taxanes and trastuzumab.
Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).T-DM1 is an antibody drug conjugate that combines trastuzumab with emtansine via a stable thioether linker. Any untreated brain lesions >2 cm in size. CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), subjects must not have any of the following:. 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). 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 tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions. (ii) Other sites of evaluable disease are present (i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 21 days prior to first dose, or time since surgical resection is at least 28 days. Subjects 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:. 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. (b) Untreated brain metastases not needing immediate local therapy CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), subjects must have at least one of the following:. ECOG performance status score of 0 or 1. Measurable or non-measurable disease assessable by RECIST v1.1. Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy. History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination. Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory. HER2-positive Breast Cancer Seattle Genetics Breast Neoplasms Tucatinib Tucatinib + T-DM1 After completion of study treatment and after occurrence of disease progression, subjects in both arms of the study will continue to be followed for survival until study closure or withdrawal of consent. Study treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. While on study treatment, subjects will be assessed for progression every 6 weeks for the first 24 weeks, and every 9 weeks thereafter, irrespective of dose holds or interruptions. Subjects will be randomized in a 1:1 manner to receive 21-day cycles of either tucatinib or placebo in combination with T-DM1. Prior pertuzumab treatment is permitted, but not required. This study is designed to evaluate the efficacy and safety of tucatinib in combination with T-DM1 in subjects with unresectable locally-advanced or metastatic HER2+ breast cancer who have had prior treatment with a taxane and trastuzumab in any setting. 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) Details Patients will get T-DM1 injections from the study site staff on the first day of every cycle. Patients will swallow tucatinib pills or placebo pills two times every day. All patients in the study will get T-DM1, a drug that is often used to treat this cancer. This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery. 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.
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