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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04538742
Collaborator
Daiichi Sankyo Company, Limited (Other)
450
Enrollment
101
Locations
8
Arms
52
Anticipated Duration (Months)
4.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
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

Study Type:
Interventional
Anticipated Enrollment :
450 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.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 :
Dec 28, 2020
Anticipated Primary Completion Date :
Apr 30, 2025
Anticipated Study Completion Date :
Apr 30, 2025

Arms and Interventions

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 Names:
  • DS-8201a, T-DXd

    • Drug: Durvalumab
    Durvalumab: administered as an IV infusion
    Other Names:
  • MEDI4736

    		•
    Experimental: Module 2- T-DXd and Pertuzumab

    T-DXd and Pertuzumab

    Drug: Trastuzumab deruxtecan
    T-DXd: administered as an IV infusion
    Other Names:
  • 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 Names:
  • 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 Names:
  • DS-8201a, T-DXd

    • Drug: Durvalumab
    Durvalumab: administered as an IV infusion
    Other Names:
  • 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 Names:
  • 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 Names:
  • DS-8201a, T-DXd

    • Drug: Tucatinib
    Tucatinib administered orally (tablet) twice daily
    Other Names:
  • 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 Names:
  • DS-8201a, T-DXd

    • Drug: Tucatinib
    Tucatinib administered orally (tablet) twice daily
    Other Names:
  • 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 Names:
  • DS-8201a, T-DXd

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Occurrence of adverse events (AEs)- Part 1 [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 [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 [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 [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 [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 [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 [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 [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 [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) [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 [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 [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 [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 [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 [Up to follow-up period, approximately 53 months]

      Percentage of patients who develop ADA for trastuzumab deruxtecan

    12. Immunogenicity of Durvalumab [Up to follow-up period, approximately 53 months]

      Percentage of patients who develop ADA for durvalumab

    13. Immunogenicity of Pertuzumab [Up to follow-up period, approximately 53 months]

      Percentage of patients who develop ADA for pertuzumab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)
    1. 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

    Locations

    Site City State Country Postal Code
    1 Research Site West Hollywood California United States 90048
    2 Research Site Fort Myers Florida United States 33901
    3 Research Site Saint Petersburg Florida United States 33705
    4 Research Site Baton Rouge Louisiana United States 70809
    5 Research Site Saint Paul Minnesota United States 55101
    6 Research Site Basking Ridge New Jersey United States 07920
    7 Research Site Middletown New Jersey United States 07748
    8 Research Site Montvale New Jersey United States 07645
    9 Research Site Commack New York United States 11725
    10 Research Site Harrison New York United States 10604
    11 Research Site Long Island City New York United States 11101
    12 Research Site New York New York United States 10016
    13 Research Site New York New York United States 10065
    14 Research Site Uniondale New York United States 11553
    15 Research Site Durham North Carolina United States 27710
    16 Research Site Cincinnati Ohio United States 45219
    17 Research Site Columbus Ohio United States 43219
    18 Research Site Providence Rhode Island United States 02903
    19 Research Site Nashville Tennessee United States 37203
    20 Research Site Fort Worth Texas United States 76104
    21 Research Site Fairfax Virginia United States 22031
    22 Research Site Melbourne Australia 3000
    23 Research Site Barretos Brazil 14784-400
    24 Research Site Belo Horizonte Brazil 30150-270
    25 Research Site Natal Brazil 59075-740
    26 Research Site Porto Alegre Brazil 90610-000
    27 Research Site Porto Alegre Brazil 91350-200
    28 Research Site Rio de Janeiro Brazil 20560-120
    29 Research Site Sao Paulo Brazil 01317-001
    30 Research Site Sao Paulo Brazil 04029-000
    31 Research Site Sorocaba Brazil 18030-510
    32 Research Site Edmonton Alberta Canada T6G 1Z2
    33 Research Site Montreal Quebec Canada H2X 0A9
    34 Research Site Montreal Quebec Canada H3T 1E2
    35 Research Site Quebec Canada G1S 4L8
    36 Research Site Toronto Canada M5G 2M9
    37 Research Site Dijon France 21079
    38 Research Site Marseille France 13273
    39 Research Site Villejuif Cedex France 94805
    40 Research Site Berlin Germany 12200
    41 Research Site Bottrop Germany 46236
    42 Research Site Düsseldorf Germany 40225
    43 Research Site Erlangen Germany 91054
    44 Research Site Halle Germany 6120
    45 Research Site München Germany 80637
    46 Research Site München Germany 81675
    47 Research Site Recklinghausen Germany 45659
    48 Research Site Würzburg Germany 97080
    49 Research Site Gurgaon India 122001
    50 Research Site Madurai India 625107
    51 Research Site Mumbai India 400012
    52 Research Site Mumbai India 400053
    53 Research Site Rohini India 110 085
    54 Research Site Bologna Italy 40138
    55 Research Site Milan Italy 20141
    56 Research Site Napoli Italy 80131
    57 Research Site Rome Italy 168
    58 Research Site Busan Korea, Republic of 49241
    59 Research Site Seoul Korea, Republic of 02841
    60 Research Site Seoul Korea, Republic of 03080
    61 Research Site Seoul Korea, Republic of 05505
    62 Research Site Seoul Korea, Republic of 06351
    63 Research Site Bydgoszcz Poland 85-796
    64 Research Site Koszalin Poland 75-581
    65 Research Site Lublin Poland 20-090
    66 Research Site Rzeszów Poland 35-055
    67 Research Site Warszawa Poland 02-034
    68 Research Site Łódź Poland 90-242
    69 Research Site Moscow Russian Federation 105229
    70 Research Site Moscow Russian Federation 109240
    71 Research Site Moscow Russian Federation 111123
    72 Research Site Moscow Russian Federation 115478
    73 Research Site Moscow Russian Federation 117997
    74 Research Site Moscow Russian Federation 121205
    75 Research Site Moscow Russian Federation 143423
    76 Research Site Saint Petersburg Russian Federation 195271
    77 Research Site Sankt-Peterburg Russian Federation 197758
    78 Research Site Barcelona Spain 08003
    79 Research Site L'Hospitalet de Llobregat Spain 08908
    80 Research Site Madrid Spain 28007
    81 Research Site Madrid Spain 28050
    82 Research Site Sevilla Spain 41013
    83 Research Site Hualien Taiwan 970
    84 Research Site Tainan Taiwan 704
    85 Research Site Taipei City Taiwan 114
    86 Research Site Taipei Taiwan 10048
    87 Research Site Taipei Taiwan 10449
    88 Research Site Taipei Taiwan 11217
    89 Research Site Taipei Taiwan 235
    90 Research Site Taoyuan City Taiwan 333
    91 Research Site Ankara Turkey 6100
    92 Research Site Edirne Turkey 22030
    93 Research Site Istanbul Turkey 34662
    94 Research Site Istanbul Turkey 34722
    95 Research Site Izmir Turkey 35100
    96 Research Site Buckhurst Hill United Kingdom IG9 5HX
    97 Research Site Cambridge United Kingdom CB2 2QQ
    98 Research Site Glasgow United Kingdom G12 0YN
    99 Research Site London United Kingdom EC1A 7BE
    100 Research Site London United Kingdom SE19RT
    101 Research Site Oxford United Kingdom OX3 7LE

    Sponsors and Collaborators

    • AstraZeneca
    • Daiichi Sankyo Company, Limited

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT04538742
    Other Study ID Numbers:
    • D967JC00001
    First Posted:
    Sep 4, 2020
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Breast Neoplasms
    Paclitaxel
    Trastuzumab
    Durvalumab
    Pertuzumab
    Tucatinib

    Study Results

    No Results Posted as of Aug 4, 2022