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A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer (DB-07)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04538742
Recruitment Status : Recruiting
First Posted : September 4, 2020
Last Update Posted : February 21, 2023
Sponsor:
Collaborator:
Daiichi Sankyo Company, Limited
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
DESTINY-Breast07 will investigate the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) in combination with other anti-cancer agents in patients with HER2-positive Metastatic Breast Cancer

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Trastuzumab deruxtecan Drug: Durvalumab Drug: Paclitaxel Drug: Pertuzumab Drug: Tucatinib Phase 1 Phase 2

Detailed Description:

This study is modular in design allowing assessment of safety, tolerability and anti-tumour activity of T-DXd in combination with other anti-cancer agents. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the recommended Phase 2 dose (RP2D) determined in Part 1 will be used for the dose-expansion in Part 2.

The target population of interest in this study is patients with HER2-positive (as per ASCO/CAP 2018 guidelines) advanced/MBC inclusive of patients with active and stable brain metastases. Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 245 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The study will consist of 2 phases: a dose escalation phase (Part 1) and a dose expansion phase (Part 2). Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later.Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)
Actual Study Start Date : December 28, 2020
Estimated Primary Completion Date : February 26, 2025
Estimated Study Completion Date : December 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Module 1- T-DXd and Durvalumab
T-DXd and Durvalumab
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd

Drug: Durvalumab
Durvalumab: administered as an IV infusion
Other Name: MEDI4736
Experimental: Module 2- T-DXd and Pertuzumab
T-DXd and Pertuzumab
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd

Drug: Pertuzumab
Pertuzumab: administered as an IV infusion
Experimental: Module 3- T-DXd and Paclitaxel
T-DXd and Paclitaxel
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd

Drug: Paclitaxel
Paclitaxel: administered as an IV infusion
Experimental: Module 4- T-DXd and Durvalumab and Paclitaxel
T-DXd and Durvalumab and Paclitaxel
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd

Drug: Durvalumab
Durvalumab: administered as an IV infusion
Other Name: MEDI4736

Drug: Paclitaxel
Paclitaxel: administered as an IV infusion
Experimental: Module 0- T-DXd
T-DXd
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd
Experimental: Module 5 - T-DXd and Tucatanib
T-DXd and tucatinib
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd

Drug: Tucatinib
Tucatinib administered orally (tablet) twice daily
Other Name: ONT-380
Experimental: Module 6 - T-DXd and Tucatinib
T-DXd and tucatinib in patients with active brain metastases (Part 2 Only)
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd

Drug: Tucatinib
Tucatinib administered orally (tablet) twice daily
Other Name: ONT-380
Experimental: Module 7 - T-DXd
T-DXd monotherapy in patients with active brain metastases (Part 2 Only)
 Drug: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion
Other Name: DS-8201a, T-DXd


Outcome Measures
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Primary Outcome Measures :
  1. Occurrence of adverse events (AEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 53 months ]
    Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0

  2. Occurrence of serious adverse events (SAEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 53 months ]
    Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0

  3. Occurrence of adverse events (AEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 53 months ]
    Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0

  4. Occurrence of serious adverse events (SAEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 53 months ]
    Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0


Secondary Outcome Measures :
  1. Objective Response Rate (ORR)- Part 1 and Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
    ORR is defined as the proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1.

  2. Progression Free Survival (PFS)- Part 1 and Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
    PFS is defined as time from the date of randomization until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.

  3. Progression Free Survival 2 (PFS2)- Part 2 [ Time Frame: Assessed up to approximately 53 months ]
    PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice.

  4. Duration of Response (DoR)- Part 2 [ Time Frame: Until progression, assessed up to approximately 53 months ]
    DoR is defined as time from the date of first documented response until the date of documented progression or death in the absence of disease progression.

  5. Overall Survival (OS)- Part 2 [ Time Frame: Until death, assessed up to approximately 53 months ]
    OS is defined as time from the date of randomisation until the date of death due to any cause.

  6. Serum Concentration of Trastuzumab Deruxtecan (T-DXd) [ Time Frame: While on study drug up to study completion, approximately 53 months ]
    Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration

  7. Serum Concentration of Durvalumab [ Time Frame: While on study drug up to study completion, approximately 53 months ]
    Determination of durvalumab concentration in serum at different time points after administration

  8. Serum Concentration of Pertuzumab [ Time Frame: While on study drug up to study completion, approximately 53 months ]
    Determination of pertuzumab concentration in serum at different time points after administration

  9. Plasma Concentration of Paclitaxel [ Time Frame: While on study drug up to study completion, approximately 53 months ]
    Determination of paclitaxel concentration in plasma at different time points after administration

  10. Plasma Concentration of Tucatinib [ Time Frame: While on study drug up to study completion, approximately 53 months ]
    Determination of tucatinib concentration in plasma at different time points after administration

  11. Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 53 months ]
    Percentage of patients who develop ADA for trastuzumab deruxtecan

  12. Immunogenicity of Durvalumab [ Time Frame: Up to follow-up period, approximately 53 months ]
    Percentage of patients who develop ADA for durvalumab

  13. Immunogenicity of Pertuzumab [ Time Frame: Up to follow-up period, approximately 53 months ]
    Percentage of patients who develop ADA for pertuzumab


Eligibility Criteria
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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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Patients must be at least 18 years of age

  • Pathologically documented breast cancer that:

    1. Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
    2. HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment. The local HER2 result must be from a tumour sample obtained in the metastatic setting.
    3. Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
  • Patient must have adequate tumor sample from the metastatic setting for biomarker assessment
  • ECOG Performance Status of 0 or 1

  • Part 1

    1. Disease progression on or after the last systemic therapy prior to starting study treatment
    2. At least 1 prior treatment line in metastatic setting required.

  • Part 2 (Modules 0 - 5)

    a) No prior lines of therapy for advanced/MBC allowed

  • Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed

CNS Inclusion

  • Modules 0 - 5 Patients must have no brain metastases or stable brain metastases.
  • Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy

Key Exclusion Criteria:

  • Uncontrolled or significant cardiovascular disease
  • Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
  • Lung-specific intercurrent clinically significant illnesses
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
  • Spinal cord compression or a history of leptomeningeal carcinomatosis
  • Prior treatment with immune checkpoint inhibitors
  • Prior treatment with an ADC containing a topoisomerase I inhibitor
  • Prior treatment with tucatinib

CNS Exclusion

  • Modules 0 - 5: Has untreated brain metastasis
  • Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy
Contacts and Locations
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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): NCT04538742


Contacts
Layout table for location contacts
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

Locations
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Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo Company, Limited
More Information
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Additional Information:

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04538742    
Other Study ID Numbers: D967JC00001
First Posted: September 4, 2020    Key Record Dates
Last Update Posted: February 21, 2023
Last Verified: February 2023
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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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 deidentified 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Breast Cancer
HER2-positive
Brain Metastases
Trastuzumab Deruxtecan
 T-DXd
DS-8201a
DESTINY-Breast07
Anti-HER2 Antibody Drug Conjugate (ADC)
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Durvalumab
Pertuzumab
Tucatinib
Trastuzumab deruxtecan
Antineoplastic Agents, Phytogenic
 Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors