Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

NCT03734029 · tracked via the Priya Life Science China tracker

Sponsor

Daiichi Sankyo

Phase

Phase 3

Started

2018-12-27

Last updated

2025-10-06

Condition(s) studied

Breast Cancer

Investigational drug(s) / intervention(s)

Trastuzumab deruxtecan (DS-8201a)CapecitabineEribulinGemcitabinePaclitaxelNab-paclitaxel

Trastuzumab deruxtecan (DS-8201a): DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously

Capecitabine: Administered according to label, as one option for Physician's Choice (determined before randomization)

Eribulin: Administered according to label, as one option for Physician's Choice (determined before randomization)

Gemcitabine: Administered according to label, as one option for Physician's Choice (determined before randomization)

Paclitaxel: Administered according to label, as one option for Physician's Choice (determined before randomization)

Nab-paclitaxel: Administered according to label, as one option for Physician's Choice (determined before randomization)

Study summary

This study will compare DS-8201a to physician choice standard treatment.

Participants must have HER2-low breast cancer that has been treated before.

Participants' cancer:

* Cannot be removed by an operation
* Has spread to other parts of the body

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

Inclusion Criteria: * Is the age of majority in their country * Has pathologically documented breast cancer that: 1. Is unresectable or metastatic 2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) 3. Is HR-positive or HR-negative 4. Has progressed on, and would no longer benefit from, endocrine therapy 5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting 6. 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) * Has documented radiologic progression (during or after most recent treatment) * Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for: 1. assessment of HER2 status 2. assessment of post-treatment status * Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1 * Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions * Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels) Exclusion Criteria: * Is ineligible for all options in the physician's choice arm * Has breast cancer ever assessed with high-HER2 expression * Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate * Has uncontrolled or significant cardiovascular disease * Has spinal cord compression or clinically active central nervous system metastases * Has 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 * Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study

Primary outcome measure(s)

Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer — From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Trial sites (208)

Facility	City	Region
Ironwood Cancer & Research Centers - Chandler II	Chandler	Arizona
Banner MD Anderson Cancer Center	Gilbert	Arizona
Cancer Treatment Centers of America at Western Regional Medical Center	Goodyear	Arizona
UCLA School of Medicine	Los Angeles	California
Stanford Cancer Institute	Palo Alto	California
Cancer Care Associates Medical Group, Inc. TORI	Redondo Beach	California
University of California at San Francisco (PARENT)	San Francisco	California
Eastern Connecticut Hematology/Oncology Assoc.	Norwich	Connecticut
Christiana Care Health Services, Inc.	Newark	Delaware
Sylvester Comprehensive Cancer Center - Deerfield Beach	Boca Raton	Florida
Florida Cancer Specialists (South Region)	Fort Myers	Florida
Memorial Healthcare System MRH Cancer Center	Hollywood	Florida
Orlando Health, Inc.	Orlando	Florida
Moffitt Cancer Center -Tampa	Tampa	Florida
Cancer Treatment Centers of America-Georgia	Newnan	Georgia
University of Chicago Medical Center	Chicago	Illinois
Cancer Treatment Centers of America	Zion	Illinois
Cancer Center of Kansas	Wichita	Kansas
Touro Infirmary	New Orleans	Louisiana
Dana-Farber Cancer Institute	Boston	Massachusetts
Henry Ford Hospital	Detroit	Michigan
Saint Luke's Hospital of Kansas City	Kansas City	Missouri
Saint Barnabas Medical Center	Livingston	New Jersey
New York University Medical Center	New York	New York
Memorial Sloan Kettering Hospital	New York	New York
Weill Cornell Medicine Breast Center	New York	New York
The Cleveland Clinic Foundation	Cleveland	Ohio
Oregon Health & Science University	Portland	Oregon
Allegheny General Hospital	Pittsburgh	Pennsylvania
University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania
St Francis Hospital	Greenville	South Carolina
Brig Center for Cancer Care and Survivorship	Knoxville	Tennessee
Baptist Cancer Center	Memphis	Tennessee
Tennessee Oncology - Skyline Satellite	Nashville	Tennessee
BloomTrials Clinical Research, LLC	Dallas	Texas
The Methodist Hospital Research Institute	Houston	Texas
University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics	Houston	Texas
Virginia Cancer Specialists	Fairfax	Virginia
Medizinische Universität Innsbruck	Innsbruck	Austria
Kepler Universitätsklinikum	Linz	Austria

+ 168 more sites — see the full list on the official registry below.

More Daiichi Sankyo trials in China

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First-in-Human Study of DS-3939a in Participants With Advanced Solid Tumors Recruiting

A Study to Assess the Effectiveness of Trastuzumab Deruxtecan in Chinese Breast Cancer Patients (REFRESH) Recruiting

Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Active, not recruiting

Other trials for the same condition

Super-Hypofractionated Partial Breast Irradiation Recruiting

A Study of GNC-077 in Patients With Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors Recruiting

A Study on the Efficacy and Safety of Switching Between Two Targeted Strategies, HP+Chemotherapy and HPy+Chemotherapy, After Treatment Progression in HER-2 Positive Advanced or Metastatic Breast Cancer Recruiting

Study Comparing EC-T Verses PCb in the Adjuvant Chemotherapy of Non-triple Negative Breast Cancer Active, not recruiting

A Study to Estimate Effect of Formulation and Food on Relative Bioavailability of HRS-6209 in Healthy Participants Active, not recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03734029 on ClinicalTrials.gov ↗ ← All trials in China