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

NCT04494425 · tracked via the Priya Life Science UK tracker

Sponsor

AstraZeneca

Phase

Phase 3

Started

2020-07-24

Last updated

2026-03-04

Condition(s) studied

Advanced or Metastatic Breast Cancer

Investigational drug(s) / intervention(s)

Trastuzumab deruxtecanCapecitabinePaclitaxelNab-Paclitaxel

Trastuzumab deruxtecan: Trastuzumab deruxtecan by intravenous infusion

Capecitabine: Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.

Paclitaxel: Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.

Nab-Paclitaxel: Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

Study summary

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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

105 Years

Healthy volunteers

Key Inclusion Criteria: * Patients must be ≥18 years of age * Pathologically documented breast cancer that: 1. is advanced or metastatic 2. has 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) 3. 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 4. was never previously HER2-positive 5. 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: 1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or 2. disease 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 Key Exclusion Criteria: * Ineligible for all options in the investigator's choice chemotherapy arm * Lung-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)

Primary outcome measure(s)

Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population — Response evaluations performed at screening, every 6 weeks (q6w) ± 1 week from randomization for 48 weeks, and then every 9 weeks (q9w) ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.

Trial sites (293)

Facility	City	Region
Research Site	Scottsdale	Arizona
Research Site	Springdale	Arkansas
Research Site	Duarte	California
Research Site	Los Angeles	California
Research Site	Aurora	Colorado
Research Site	Lakewood	Colorado
Research Site	Washington D.C.	District of Columbia
Research Site	Jacksonville	Florida
Research Site	Kansas City	Kansas
Research Site	Louisville	Kentucky
Research Site	Bethesda	Maryland
Research Site	Boston	Massachusetts
Research Site	Detroit	Michigan
Research Site	Rochester	Minnesota
Research Site	St Louis	Missouri
Research Site	Summit	New Jersey
Research Site	Westbury	New York
Research Site	Columbus	Ohio
Research Site	Pittsburgh	Pennsylvania
Research Site	Nashville	Tennessee
Research Site	Austin	Texas
Research Site	Dallas	Texas
Research Site	Houston	Texas
Research Site	Houston	Texas
Research Site	Norfolk	Virginia
Research Site	Seattle	Washington
Research Site	Madison	Wisconsin
Research Site	Buenos Aires	Argentina
Research Site	CABA	Argentina
Research Site	CABA	Argentina
Research Site	CABA	Argentina
Research Site	Ciudad de Buenos Aires	Argentina
Research Site	Córdoba	Argentina
Research Site	La Plata	Argentina
Research Site	Mar del Plata	Argentina
Research Site	Rosario	Argentina
Research Site	Rosario	Argentina
Research Site	Adelaide	Australia
Research Site	Birtinya	Australia
Research Site	Darlinghurst	Australia

+ 253 more sites — see the full list on the official registry below.

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 NCT04494425 on ClinicalTrials.gov ↗ ← All trials in the UK