A Phase 3 interventional study of Trastuzumab deruxtecan and Placebo in Breast Cancer; HER2-positive; Metastatic, sponsored by AstraZeneca. Active, not recruiting at 283 sites in 27 countries. Open to participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2026-07-30.
Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment
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.
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 1,157 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Pathologically documented breast cancer that:
Key Exclusion Criteria:
Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo
Drug: Trastuzumab deruxtecan · Drug: Placebo
Trastuzumab deruxtecan (T-DXd) plus pertuzumab
Drug: Trastuzumab deruxtecan · Drug: Pertuzumab
Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)
Drug: Taxane · Drug: Pertuzumab · Drug: Trastuzumab
Administered by intravenous infusion
Also known as: DS-8201a; T-DXd
Administered by intravenous infusion
Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion
Administered by intravenous infusion
Administered by intravenous infusion
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment
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.
Time frame: Until progression or death, assessed up to approximately 60 months
Progression Free Survival (PFS) by Investigator assessment
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.
Time frame: Until progression or death, assessed up to approximately 60 months
Overall Survival (OS)
OS is defined as the time from randomisation until the date of death due to any cause.
Time frame: Until death, assessed up to approximately 104 months
Objective Response Rate (ORR) by BICR and Investigator assessment
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.
Time frame: Until progression or death (in the absence of progression), assessed up to approximately 60 months
Duration of Response (DoR) by BICR and Investigator Assessment
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.
Time frame: Until progression or death (in the absence of progression), assessed up to approximately 60 months
Time to second progression or death (PFS2) by Investigator assessment
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.
Time frame: Assessed up to approximately 104 months
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'.
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.
Time frame: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
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.
Time frame: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
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.
Time frame: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
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.
Time frame: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
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.
Time frame: Assessed up to approximately 60 months
To assess patient-reported treatment tolerability
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.
Time frame: Assessed up to approximately 60 months
Serum concentration of trastuzumab deruxtecan and pertuzumab
Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum.
Time frame: Up to Cycle 6, approximately Week 18; each cycle is 21 days
Immunogenicity of trastuzumab deruxtecan.
Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan.
Time frame: Up to follow-up period, approximately 60 months
Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab
Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm
Time frame: Assessed up to approximately 60 months
Showing the first 100 of 283 sites across 27 countries.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting information: Study protocol, Sap
This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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