This trial studies a type of advanced breast cancer defined as hormone receptor HR-positive/HER2-negative and classified as non-luminal by gene expression profiling (PAM50). Patients will be treated with trastuzumab deruxtecan (T-DXd) or with physician's choice of CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET). The main purpose of the study is to analyze the efficacy of T-DXd in patients who have HR-positive and HER2-low/ultralow advanced breast cancer classified as non-luminal subtype.
Patients must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
Female or male patients ≥ 18 years of age at the time of signing ICF.
ECOG performance status of 0-1.
Minimum life expectancy of ≥ 12 weeks at screening.
Current participation in another therapeutic clinical trial, except other translational studies.
Treatment with approved or investigational cancer therapy within 3 weeks prior to initiation of study drug.
Treatment with chloroquine/hydroxychloroquine within 14 days prior to initiation of study drug.
Have previously been treated with T-DXd and/or fulvestrant. Note: patients who experienced relapse after more than 1 year from completion of fulvestrant are eligible.
Parallel
Trastuzumab deruxtecan (T-DXd, DS-8201a)
DrugPatients will receive T-DXd 5.4 mg/kg body weight administered as an intravenous (IV) infusion on Day 1 (D1) of each 21-day cycle. The initial dose will be administered as a 90-minute IV infusion.
CDK4/6i plus ET
DrugPatients will receive physician's choice of CDK4/6 inhibitor (CDK4/6i) including palbociclib, ribociclib, and abemaciclib; physician's choice of endocrine therapy (ET) including fulvestrant, letrozole, anastrozole, and exemestane.
Progression-free survival (PFS)
PFS, defined as the period from randomization date to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1. in HER2-low patients.
Progression-free survival (PFS)
PFS, defined as the period from randomization date to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1 in all patients.
Overall survival (OS)
OS, defined as the period from randomization date to death from any cause, as determined locally by the investigator (in all patients and HER2-low population).
Objective response rate (ORR)
ORR, defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population).
Clinical benefit rate (CBR)
CBR, defined as the rate of patients with objective response (CR or PR), or stable disease for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population).
Duration of response (DoR)
DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population).
