NCT04784715 · CITED IN SOURCE DOCUMENTS

Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)

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: 2026-07-30

The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.

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What did the study report?

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

No posted result sections were captured. Registered plans do not establish that a treatment works.

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. is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+) 3. is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting * No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if \> 6 months from treatment to metastatic diagnosis. * Has protocol-defined adequate organ and bone marrow function * ECOG performance status 0 or 1 Key Exclusion Criteria: * Ineligible for any of the agents on the study. * Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results * Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study. * Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening * Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo
intervention Names
Drug: Trastuzumab deruxtecan
Drug: Placebo
label
Arm A
type
EXPERIMENTAL
description
Trastuzumab deruxtecan (T-DXd) plus pertuzumab
intervention Names
Drug: Trastuzumab deruxtecan
Drug: Pertuzumab
label
Arm B
type
EXPERIMENTAL
description
Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)
intervention Names
Drug: Taxane
Drug: Pertuzumab
Drug: Trastuzumab
label
Arm C
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm A
Arm B
description
Administered by intravenous infusion
name
Trastuzumab deruxtecan
other Names
DS-8201a; T-DXd
type
DRUG
arm Group Labels
Arm A
description
Administered by intravenous infusion
name
Placebo
type
DRUG
arm Group Labels
Arm C
description
Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion
name
Taxane
type
DRUG
arm Group Labels
Arm B
Arm C
description
Administered by intravenous infusion
name
Pertuzumab
type
DRUG
arm Group Labels
Arm C
description
Administered by intravenous infusion
name
Trastuzumab
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

intervention Model Description

Study will consist of three arms: Arm A - trastuzumab deruxtecan with pertuzumab-matching placebo Arm B - trastuzumab deruxtecan with pertuzumab Arm C - standard of care (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab)

masking Info

masking: NONE
masking Description: This study is open-label with respect to the control arm. Pertuzumab/placebo in the experimental arms will be blinded to the investigator and patients. The study will be "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: 1157
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Defined as time from date of randomisation until the date of objective radiological disease progression according to Blinded Independent Central Review (BICR) using RECIST 1.1 or death by any cause.
measure
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment
time Frame
Until progression or death, assessed up to approximately 60 months

secondary Outcomes

description
Defined as time from date of randomisation until the date of objective radiological disease progression according to Investigator using RECIST 1.1 or death by any cause.
measure
Progression Free Survival (PFS) by Investigator assessment
time Frame
Until progression or death, assessed up to approximately 60 months
description
OS is defined as the time from randomisation until the date of death due to any cause.
measure
Overall Survival (OS)
time Frame
Until death, assessed up to approximately 104 months
description
ORR is defined as The proportion of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1.
measure
Objective Response Rate (ORR) by BICR and Investigator assessment
time Frame
Until progression or death (in the absence of progression), assessed up to approximately 60 months
description
DoR is defined as the time from date of first detection of objective response until the date of objective radiological disease progression according to BICR and investigator assessment using RECIST 1.1 or death in the absence of progression.
measure
Duration of Response (DoR) by BICR and Investigator Assessment
time Frame
Until progression or death (in the absence of progression), assessed up to approximately 60 months
description
PFS2 is defined as the time from randomisation until the date of tumor progression on next-line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy after the first progression) or death from any cause; second progression will be defined according to local standard clinical practice.
measure
Time to second progression or death (PFS2) by Investigator assessment
time Frame
Assessed up to approximately 104 months
description
Pain progression: Time to sustained deterioration of European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Pain Scale. Scores range from 0-100 based on 2 items with responses ranging from 1-4. A lower score would mean better outcome.
measure
To assess the effect of T-DXd ± pertuzumab relative to THP in terms of patient-reported pain in participants with HER2 positive, first-line mBC'.
time Frame
Assessed up to approximately 60 months
description
Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, general cancer module (EORTC QLQ-C30), score of 1-4. A lower score would mean better outcome.
measure
To assess patient-reported treatment tolerability
time Frame
Assessed up to approximately 60 months
description
Proportion of patients reporting different levels of overall tolerability as measured by the Patient Global Impression of Treatment Tolerability (PGI-TT), score of 0-4. A lower score would mean a better outcome.
measure
To assess patient-reported treatment tolerability
time Frame
Assessed up to approximately 60 months
description
Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, breast cancer module (EORTC QLQ-BR45), score of 1-4. A lower score would mean better outcome.
measure
To assess patient-reported treatment tolerability
time Frame
Assessed up to approximately 60 months
description
Proportion of participants experiencing treatment related symptoms as measured by selected items from the Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events (PRO-CTCAE). PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present). A lower score would mean a better outcome.
measure
To assess patient-reported treatment tolerability
time Frame
Assessed up to approximately 60 months
description
The proportion of participants with maintained or improved physical function while on treatment, based on the EORTC QLQ-C30 Physical Functioning scale. Scores range from 0-100, based on 5 items with responses ranging from 1-4. A higher score would mean a better outcome.
measure
To assess patient-reported treatment tolerability
time Frame
Assessed up to approximately 60 months
description
Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum.
measure
Serum concentration of trastuzumab deruxtecan and pertuzumab
time Frame
Up to Cycle 6, approximately Week 18; each cycle is 21 days

Full study description

brief Summary: The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.
detailed Description: Eligible participants will be those diagnosed with HER2-positive (IHC 3+ or ISH+), metastatic breast cancer, who have received no prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer. The study aims to evaluate the efficacy, and safety of trastuzumab deruxtecan, alone or with pertuzumab, compared with the standard of care treatment (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab). 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
Tolaney SM, Jiang Z, Zhang Q, Barroso-Sousa R, Park YH, Rimawi MF, Saura C, Schneeweiss A, Toi M, Chae YS, Kemal Y, Chaudhari M, Sendur MAN, Yamashita T, Casalnuovo M, Danso MA, Liu J, Shetty J, Herbolsheimer P, Loibl S; DESTINY-Breast09 Trial Investigators. Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2026 Feb 5;394(6):551-562. doi: 10.1056/NEJMoa2508668. Epub 2025 Oct 29.
pmid
41160818
type
DERIVED