This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04784715
Recruitment Status : Active, not recruiting
First Posted : March 5, 2021
Last Update Posted : February 22, 2024
Sponsor:
Collaborator:
Daiichi Sankyo
Information provided by (Responsible Party):
AstraZeneca

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Breast Cancer; HER2-positive; Metastatic Drug: Trastuzumab deruxtecan Drug: Placebo Drug: Taxane Drug: Pertuzumab Drug: Trastuzumab Phase 3

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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1156 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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: None (Open Label)
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
Official 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)
Actual Study Start Date : April 26, 2021
Estimated Primary Completion Date : March 28, 2025
Estimated Study Completion Date : December 30, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Arm A
Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo
 Drug: Trastuzumab deruxtecan
Administered by intravenous infusion
Other Name: DS-8201a; T-DXd

Drug: Placebo
Administered by intravenous infusion
Experimental: Arm B
Trastuzumab deruxtecan (T-DXd) plus pertuzumab
 Drug: Trastuzumab deruxtecan
Administered by intravenous infusion
Other Name: DS-8201a; T-DXd

Drug: Pertuzumab
Administered by intravenous infusion
Active Comparator: Arm C
Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)
 Drug: Taxane
Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion

Drug: Pertuzumab
Administered by intravenous infusion

Drug: Trastuzumab
Administered by intravenous infusion


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04784715


Locations
Show Show 285 study locations
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04784715    
Other Study ID Numbers: D967UC00001
2020-004074-21 ( EudraCT Number )
First Posted: March 5, 2021    Key Record Dates
Last Update Posted: February 22, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Breast Neoplasms; Breast Diseases; Trastuzumab; Antineoplastic Agents, Phytogenic; Anti-drug conjugate; Molecular Mechanisms of Pharmacological Action;
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Pertuzumab
 Taxane
Trastuzumab deruxtecan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs