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NCT Number: NCT04784715

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

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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This study is active but is not currently recruiting participants.

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Key information

Conditions

Breast Cancer; HER2-positive; Metastatic Breast Diseases Breast Neoplasms Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Patients must be ≥18 years of age
  • Pathologically documented breast cancer that:
  • is advanced or metastatic
  • is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+)
  • 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

Treatment and study plan

Trastuzumab Deruxtecan

Drug

Administered by intravenous infusion

Other names: DS-8201a; T-DXd

Placebo

Drug

Administered by intravenous infusion

taxane

Drug

Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion

Pertuzumab

Drug

Administered by intravenous infusion

Trastuzumab

Drug

Administered by intravenous infusion

Primary outcomes

  1. Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment

    Time frame: Until progression or death, assessed up to approximately 60 months

    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.

Secondary outcomes

  1. Progression Free Survival (PFS) by Investigator assessment

    Time frame: Until progression or death, assessed up to approximately 60 months

    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.

  2. Overall Survival (OS)

    Time frame: Until death, assessed up to approximately 104 months

    OS is defined as the time from randomisation until the date of death due to any cause.

  3. 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

    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.

  4. 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

    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.

  5. Time to second progression or death (PFS2) by Investigator assessment

    Time frame: Assessed up to approximately 104 months

    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.

  6. 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

    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.

  7. To assess patient-reported treatment tolerability

    Time frame: Assessed up to approximately 60 months

    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.

  8. To assess patient-reported treatment tolerability

    Time frame: Assessed up to approximately 60 months

    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.

  9. To assess patient-reported treatment tolerability

    Time frame: Assessed up to approximately 60 months

    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.

  10. To assess patient-reported treatment tolerability

    Time frame: Assessed up to approximately 60 months

    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.

  11. To assess patient-reported treatment tolerability

    Time frame: Assessed up to approximately 60 months

    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.

  12. Serum concentration of trastuzumab deruxtecan and pertuzumab

    Time frame: Up to Cycle 6, approximately Week 18; each cycle is 21 days

    Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum.

  13. Immunogenicity of trastuzumab deruxtecan.

    Time frame: Up to follow-up period, approximately 60 months

    Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan.

  14. Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab

    Time frame: Assessed up to approximately 60 months

    Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Daiichi Sankyo

Registry information

Official study title

Phase III Study of Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive, First-line Metastatic Breast Cancer (DESTINY-Breast09)

Important dates

Study start
2021
Primary completion
2026
Study completion
2029
First posted
Mar 5, 2021
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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