DS8201-A-U303 (DESTINY-Breast04): A Phase 3, multicenter, randomized, open-label, active-controlled trial of DS-8201a, an anti-HER2-antibody drug conjugate (ADC), versus treatment of physician’s choice for HER2-low, unresectable and/or metastatic breast cancer subjects
Description
This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants. The sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.
Status
Accepting new patients
Primary Study Objective(s)
The primary objective of this study is to compare the progression-free survival (PFS) benefit of DS-8201a to physician’s choice in HER2-low, hormone receptor (HR)-positive breast cancer, based on blinded independent central review (BICR)
Core eligibility
Note: This is only a partial list of eligibility criteria.
Including patients who:
- Are at least 18 years old
- Have pathologically documented breast cancer that:
- Is unresectable or metastatic
- Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
- Is HR-positive or HR-negative
- Has progressed on, and would no longer benefit from, endocrine therapy
- Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the metastatic setting
- Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)
- Have documented radiologic progression (during or after most recent treatment)
- Have adequate archival tumor samples available or are wiling to provide fresh biopsies prior to randomization for:
- Assessment of HER2 status
- Assessment of post-treatment status
- Have at least one protocol-defined measurable lesion
- Have protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
- Agree, if of reproductive/childbearing potential, to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least four-and one-half months after treatment (or longer, per locally approved labels)
Excluding patients who:
- Are ineligible for all options in the physician's choice arm
- Have breast cancer ever assessed with high-HER2 expression
- Have previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
- Have uncontrolled or significant cardiovascular disease
- Have spinal cord compression or clinically active central nervous system metastases
- Have a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- Have any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study
Principal Investigator(s)
Cynthia Lynch
Eugene Ahn
Damien Hansra
