NCT04494425 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-03-04

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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

→

outcome · POSTED

Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population

→

outcome · POSTED

Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population

→

outcome · POSTED

Overall Survival (OS) in the Intent-to-Treat Population

→

outcome · POSTED

Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population

→

outcome · POSTED

Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population

→

outcome · POSTED

Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population

→

outcome · POSTED

Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population

→

outcome · POSTED

Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population

→

outcome · POSTED

Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population

→

outcome · POSTED

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

→

outcome · POSTED

Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a

→

outcome · POSTED

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91

→

outcome · POSTED

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58

→

outcome · POSTED

Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score

→

outcome · POSTED

Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan

→

outcome · NOT POSTED

Time to First Subsequent Treatment or Death (TFST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population

→

outcome · NOT POSTED

Time to Second Subsequent Treatment or Death (TSST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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)
healthy Volunteers: false
maximum Age: 105 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
intervention Names
Drug: Trastuzumab deruxtecan
label
Trastuzumab deruxtecan
type
EXPERIMENTAL
description
Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
intervention Names
Drug: Capecitabine
Drug: Paclitaxel
Drug: Nab-Paclitaxel
label
Standard of Care
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Trastuzumab deruxtecan
description
Trastuzumab deruxtecan by intravenous infusion
name
Trastuzumab deruxtecan
other Names
DS-8201a; T-DXd
type
DRUG
arm Group Labels
Standard of Care
description
Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.
name
Capecitabine
type
DRUG
arm Group Labels
Standard of Care
description
Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.
name
Paclitaxel
type
DRUG
arm Group Labels
Standard of Care
description
Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion
name
Nab-Paclitaxel
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

intervention Model Description

The study consists of 2 independent open label treatment arms: trastuzumab deruxtecan and Investigator's choice chemotherapy (paclitaxel, nab-paclitaxel or capecitabine).

masking Info

masking: NONE
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.

primary Purpose

TREATMENT

Enrollment

count: 866
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
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
time Frame
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)

secondary Outcomes

description
OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
measure
Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
time Frame
From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
PFS per 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 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 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
measure
Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population
time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
measure
Overall Survival (OS) in the Intent-to-Treat Population
time Frame
From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
PFS per RECIST 1.1 assessed by Investigator 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 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 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
measure
Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR). CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
measure
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of 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 mm from nadir. Median DOR was calculated using Kaplan-Meier method.
measure
Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
measure
Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population
time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of 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 mm from nadir. Median DOR was calculated using Kaplan-Meier method.
measure
Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population
time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
PFS2 was defined as time from randomization to second progression (the earliest of the progression event subsequent to first subsequent therapy) or death; second progression was defined according to local standard clinical practice and might involve any of the following: objective radiological imaging, symptomatic progression, or death. Median PFS2 was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
measure
Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population
time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. A serious adverse event (SAE) was an AE occurring during any study phase, that fulfilled 1 or more of following criteria: resulted in death, was immediately life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was congenital abnormality or birth defect, and was an important medical event that jeopardized participant or required medical treatment to prevent 1 of outcomes listed above. TEAE was any AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiation of the study drug until the 40-day (+7 days) safety follow-up visit.
measure
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
time Frame
From first dose of study drug (Day 1) up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
description
Blood samples were collected at indicated time points to determine the concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum.
measure
Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a
time Frame
Pre-dose on Day 1 of Cycles 1, 2, 4, 6 and 8; 15 minutes post-dose on Day 1 of Cycles 1, 2 and 4; and 5 hours post-dose on Day 1 of Cycle 1 (each cycle is 21 days)
description
EORTC QLQ-C30 is a 30-item self-administered questionnaire grouped into 5 multi-item functional scales(physical,role,emotional,cognitive and social),3 multiitem symptom scales(fatigue,pain and nausea/vomiting),2-item global QoL scale,5 single items assessing additional symptoms reported by cancer participants(dyspnea,loss of appetite,insomnia,constipation and diarrhea). All but 2 questions have 4-point scales:1:not at all,2:a little,3:quite a bit,4:very much.2 questions concerning global health status and QoL have 7-point scales with responses ranging from 1:very poor to 7:excellent;higher score:better level of functioning/greater degree of symptoms.For each of 15 scales,final scores were averaged from scores of component items,transformed,range: 0 to 100;higher scores:better functioning,better health related (HR)QoL,or greater level of symptoms(higher scores:opposite interpretations for functioning/QoL and symptoms/problems).Baseline:last observed measurement prior to randomization.
measure
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91
time Frame
Baseline (Day 1) and Week 91

Full study description

brief 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.
detailed Description: Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC \>0 \<1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer. The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Source references

references

citation
Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O'Shaughnessy JA, Wildiers H, Pierga JY, Zhang Q, Saura C, Biganzoli L, Sohn J, Im SA, Levy C, Jacot W, Begbie N, Ke J, Patel G, Curigliano G; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122. doi: 10.1056/NEJMoa2407086. Epub 2024 Sep 15.
pmid
39282896
type
DERIVED
citation
Tarantino P, Tolaney SM, Curigliano G. Trastuzumab deruxtecan (T-DXd) in HER2-low metastatic breast cancer treatment. Ann Oncol. 2023 Oct;34(10):949-950. doi: 10.1016/j.annonc.2023.07.003. Epub 2023 Jul 26. No abstract available.
pmid
37499870
type
DERIVED