Unresectable/metastatic breast cancer with human epidermal growth factor receptor 2 (HER2)-positive expression MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Sponsors
Daiichi Sankyo Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adults =18 years old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old.) • Pathologically documented breast cancer that: - is unresectable or metastatic - has confirmed HER2 positive expression as determined according to American Society of Clinical Oncology – College of American Pathologists guidelines evaluated at a central laboratory. - was previously treated with T DM1. • Documented radiologic progression (during or after most recent treatment or within 6 mo after completing adjuvant therapy). • Subjects must be HER2 positive as confirmed by central laboratory assessment of most recent tumor tissue sample available. • Female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 mo after the last dose of trastuzumab deruxtecan, 6 mo after the last dose of lapatinib/capecitabine, or 7 mo after the last dose of trastuzumab/capecitabine. Male subjects must agree to inform all potential female partners that they are participating in a clinical trial of a drug that may cause birth defects. Male subjects must also agree to either avoid intercourse or that he and/or any female partner of reproductive/childbearing potential will use a highly effective form of contraception during and upon completion of the study and for at least 4.5 mo after the last dose of trastuzumab deruxtecan, 3 mo after the last dose of lapatinib/capecitabine, or 7 mo after the last dose of trastuzumab/capecitabine. • Adequate renal function, defined as: - Creatinine clearance = 30 mL/min, as calculated using the Cockcroft-Gault equation, • Adequate hepatic function, defined as: - Total bilirubin = 1.5 × upper limit of normal (ULN) if no liver metastases or =65 years) yes F.1.3.1 Number of subjects for this age range 258
Exclusion criteria
Exclusion criteria: • Ineligible for the comparator arm treatment for reasons including but not limited to the following: - Prior treatment with capecitabine. - History of any contraindication included in the approved local label for capecitabine or for both trastuzumab and lapatinib; - Concurrent treatment with any medication prohibited in the applicable approved local label for capecitabine or for both trastuzumab and lapatinib. • Prior participation in a study involving an antibody drug conjugate produced by Daiichi Sankyo. • Uncontrolled or significant cardiovascular disease, including any of the following: - History of myocardial infarction within 6 mo before randomization - History of symptomatic congestive heart failure (New York Heart Association Class II to IV) - Troponin levels consistent with myocardial infarction as defined according to the manufacturer within 28 d prior to randomization - Corrected QT interval prolongation to >470 ms (females) or >450 ms (male) based on average of screening triplicate 12 lead electrocardiogram (ECG) - Left ventricular ejection fraction (LVEF) < 50% within 28 d prior to randomization • Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. • Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. - Subjects with clinically inactive brain metastases may be included in the study. - Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare the progression-free survival (PFS) benefit of trastuzumab deruxtecan to investigator’s choice for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with T-DM1.;Secondary Objective: Key Secondary Objective: ? To compare overall survival (OS) benefit of trastuzumab deruxtecan to investigator’s choice for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with T-DM1. Other Secondary Objectives: ? To evaluate efficacy of trastuzumab deruxtecan compared to investigator’s choice on: - Confirmed objective response rate (ORR); - Duration of response (DoR); ? To further determine pharmacokinetics (PK) of trastuzumab deruxtecan. ? To further evaluate safety of trastuzumab deruxtecan compared to investigator’s choice. ? To evaluate Health Economics and Outcomes Research (HEOR) endpoints for trastuzumab deruxtecan compared to investigator’s choice.;Primary end point(s): PFS based on blinded independent central review (BICR);Timepoint(s) of evaluation of this end point: The primary analysis for PFS will be performed when approximately 372 BICR-assessed PFS events are observed or 18 months from the last subject randomized, whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoint is OS.;Timepoint(s) of evaluation of this end point: Up to 3 analyses of OS could be performed: • First interim analysis at the time of the final analysis for PFS (provided PFS is significant), at which point a total of approximately 240 OS events (55% information fraction) are expected. • If the OS interim analysis is not significant, a second interim analysis for OS is planned when approximately 304 OS events (70% information fraction) are expected. • If the second OS interim analysis is not significant, a final analysis for OS after approximately 434 OS events have been observed (expected 71 months from date of first subject to be randomized). | — |
Countries
Australia, Belgium, Brazil, Czechia, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, Spain, Turkey, United Kingdom, United States
Outcome results
None listed