Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer

Trial number:
Trial phase:
Study type:
Targeted therapy, Biomarker
Overall status:

Study start date

July, 2020

Scientific title

A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)


This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.


Patients must be ≥18 years of age

Pathologically documented breast cancer that:

is advanced or metastatichas a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested) has HER2-low or HER2 IHC >0 <1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting was never previously HER2-positive is documented HR+ disease in the metastatic setting. No prior chemotherapy for advanced or metastatic breast cancer. Has adequate tumor samples for assessment of HER2 status

Must have either:

disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor ordisease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting. Has protocol-defined adequate organ and bone marrow function


Ineligible for all options in the investigator's choice chemotherapy armLung-specific intercurrent clinically significant illnesses Uncontrolled or significant cardiovascular disease or infection Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening. Patients with spinal cord compression or clinically active central nervous system metastases Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)

Study design

Primary purpose: Treatment, Allocation: Randomized, Intervention model: Parallel Assignment, Intervention model description: The study consists of 2 independent open label treatment arms, Masking: None (Open Label), Masking description: This study is an open-label study that will be conducted "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.,


Advanced or Metastatic Breast Cancer

Other study ID numbers


Choose trial site (422)

Tan Tock Seng Hospital Singapore
11 Jln Tan Tock Seng, Level 1, Singapore 308433
National Cancer Centre Singapore
Curie Oncology (Farrer)
Farrer Park
1 Farrer Park Station Road, #09-13 to 20 Farrer Park Medical Centre, Connexion Singapore 217562