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

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ClinicalTrials.gov Identifier: NCT04784715
Recruitment Status : Recruiting
First Posted : March 5, 2021
Last Update Posted : January 17, 2023
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE February 19, 2021
First Posted Date  ICMJE March 5, 2021
Last Update Posted Date January 17, 2023
Actual Study Start Date  ICMJE April 26, 2021
Estimated Primary Completion Date December 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2021)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2022)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2021)
  • 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.
  • 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.
  • 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 percentage of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1.
  • 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.
  • 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 (after death from any cause); second progression will be defined according to local standard clinical practice.
  • Health related quality of life (HRQoL) using the EORTC QLQ-C30 [ Time Frame: Assessed up to approximately 60 months ]
    Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30
  • Time to deterioration in EORTC-QLQ-C30 scores [ Time Frame: Assessed up to approximately 60 months ]
    Time to deterioration in EORTC QLQ C30 physical and role function, global health status/QoL and pain scores.
  • Health related quality of life (HRQoL) using the EORTC QLQ-BR45 [ Time Frame: Assessed up to approximately 60 months ]
    Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BR45
  • Serum concentration of trastuzumab deruxtecan and pertuzumab [ Time Frame: Up to Cycle 8, approximately Week 24; each cycle is 21 days ]
    Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum.
  • Immunogenicity of trastuzumab deruxtecan, alone or with pertuzumab. [ Time Frame: Up to follow-up period, approximately 60 months ]
    Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan. Number and percentage of participants who develop ADA for pertuzumab
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)
Official Title  ICMJE 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)
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Breast Cancer; HER2-positive; Metastatic
Intervention  ICMJE
  • Drug: Trastuzumab deruxtecan
    Administered by intravenous infusion
    Other Name: DS-8201a; T-DXd
  • Drug: Placebo
    Administered by intravenous infusion
  • 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
Study Arms  ICMJE
  • Experimental: Arm A
    Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo
    Interventions:
    • Drug: Trastuzumab deruxtecan
    • Drug: Placebo
  • Experimental: Arm B
    Trastuzumab deruxtecan (T-DXd) plus pertuzumab
    Interventions:
    • Drug: Trastuzumab deruxtecan
    • Drug: Pertuzumab
  • Active Comparator: Arm C
    Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)
    Interventions:
    • Drug: Taxane
    • Drug: Pertuzumab
    • Drug: Trastuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 2, 2021)
1134
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2029
Estimated Primary Completion Date December 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AZ Breast Cancer Study Navigators +1-877-400-4656 AstraZeneca@CareboxHealth.com
Listed Location Countries  ICMJE Argentina,   Austria,   Belgium,   Brazil,   Canada,   China,   Denmark,   France,   Germany,   Hungary,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Peru,   Philippines,   Romania,   Russian Federation,   Saudi Arabia,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT04784715
Other Study ID Numbers  ICMJE D967UC00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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
Current Responsible Party AstraZeneca
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Daiichi Sankyo, Inc.
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP