DB-08: A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04556773
Collaborator
Daiichi Sankyo Co., Ltd. (Industry), Daiichi Sankyo Company, Limited (Other)
182
60
5
32.3
3
0.1

Study Details

Study Description

Brief Summary

DESTINY-Breast 08 will investigate the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies in patients with Metastatic HER2-low Advanced or Metastatic Breast Cancer

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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

The target population of interest in this study is patients with HER2-low (IHC 1+ or IHC 2+/ISH -) (as per ASCO/CAP 2018 guidelines) advanced/MBC. Part 1 of each module will enroll patients with locally confirmed HER2-low advanced/MBC in second-line or later (≥ 2L) settings

Part 2 of each module will enroll patients with HER2-low MBC who have either not received prior treatment, or received only 1 prior treatment (depending on the module-specific exclusion criteria) for advanced/metastatic disease

Study Design

Study Type:
Interventional
Anticipated Enrollment :
182 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The study will initially consist of 5 treatment modules, each of which includes T-DXd in combination with other anti-cancer agents. Each module will have 2 parts: a dose-finding phase (Part 1) and a dose-expansion phase (Part 2). The Part 2 dose-expansion phase will use the recommended Phase 2 dose (RP2D) for the combination, either as determined in Part 1 or from another clinical study if appropriate. For each module, patients will be centrally assigned to one of the open modules, as per the module specific criteria. In addition to safety and tolerability, this study will also assess ORR, PFS, DoR, and OS for each treatment combination.The study will initially consist of 5 treatment modules, each of which includes T-DXd in combination with other anti-cancer agents. Each module will have 2 parts: a dose-finding phase (Part 1) and a dose-expansion phase (Part 2). The Part 2 dose-expansion phase will use the recommended Phase 2 dose (RP2D) for the combination, either as determined in Part 1 or from another clinical study if appropriate. For each module, patients will be centrally assigned to one of the open modules, as per the module specific criteria. In addition to safety and tolerability, this study will also assess ORR, PFS, DoR, and OS for each treatment combination.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With Metastatic HER2-low Breast Cancer (DESTINY-Breast08)
Actual Study Start Date :
Dec 17, 2020
Anticipated Primary Completion Date :
Aug 28, 2023
Anticipated Study Completion Date :
Aug 28, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Module 1: T-DXd + capecitabine

T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use

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

    Experimental: Module 2: T-DXd + durvalumab + paclitaxel

    T-DXd: 5.4 mg/kg Q3W, intravenous use Durvalumab: 1120 mg Q3W, intravenous use Paclitaxel: 80 mg/m2 QW in 3-week cycles, intravenous use

    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
    Other Names:
  • Taxol A
  • Experimental: Module 3: T-DXd + capivasertib

    T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use

    Drug: Trastuzumab deruxtecan
    T-DXd: administered as an IV infusion
    Other Names:
  • DS-8201a, T-DXd
  • Drug: Capivasertib
    Capivasertib: administered orally
    Other Names:
  • AZD5363
  • Experimental: Module 4: T-DXd + anastrozole

    T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral

    Drug: Trastuzumab deruxtecan
    T-DXd: administered as an IV infusion
    Other Names:
  • DS-8201a, T-DXd
  • Drug: Anastrozole
    Anastrozole: administered orally
    Other Names:
  • Anastrozol
  • Experimental: Module 5: T-DXd + fulvestrant

    T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use

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

    Outcome Measures

    Primary Outcome Measures

    1. Occurrence of adverse events (AEs)- Part 1 [Up to follow-up period, approximately 24 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 24 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 24 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 24 months]

      Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0

    Secondary Outcome Measures

    1. Objective Response Rate (ORR)- Part 2 [Until progression, assessed up to approximately 24 months]

      ORR defined as the proportion of patients who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1

    2. Progression Free Survival (PFS)- Part 2 [Until progression or death, assessed up to approximately 24 months]

      PFS defined as time from the date of first dose until the date of progression as determined by the investigator at local site per RECIST 1.1, or death due to any cause

    3. Duration of Response (DoR)- Part 2 [Until progression or death, assessed up to approximately 24 months]

      DoR defined as time from the date of first documented response (which is subsequently confirmed) until the date of documented progression or death in the absence of disease progression

    4. Overall Survival (OS)- Part 2 [Until death, assessed up to approximately 24 months]

      OS defined as time from the date of first dose until the date of death by any cause

    5. Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a [While on study drug up to study completion, approximately 24 months]

      Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration

    6. Immunogenicity of trastuzumab deruxtecan [Up to follow-up period, approximately 24 months]

      Percentage of patients who develop ADA for trastuzumab deruxtecan

    7. Serum Concentration of durvalumab [While on study drug up to study completion, approximately 24 months]

      Determination of durvalumab concentration in serum at different time points after administration

    8. Immunogenicity of durvalumab [Up to follow-up period, approximately 24 months]

      Percentage of patients who develop ADAs for durvalumab

    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

    • Male or female patients who have pathologically documented breast cancer that:

    1. Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay

    2. Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥1%]) or ER and PgR negative (ER and PgR <1%) per ASCO/CAP guidelines in the metastatic setting

    • Patient must have adequate tumor sample for biomarker assessment

    • ECOG Performance Status of 0 or 1

    For patients with HR+ disease:

    Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are required.

    Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of Modules 2 and 3.

    For patients with HR- disease:

    Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no patients with HR- disease in Part 1 of Modules 4 and 5.

    Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and 3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with HR- disease in Part 2 of Modules 4 and 5.

    Key Exclusion Criteria:
    • Uncontrolled intercurrent illness

    • Uncontrolled or siginificant cardiovascular disease

    • History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

    • Lung-specific intercurrent clinically significant illnesses

    • Has spinal cord compression or clinically active central nervous system metastases

    • Active primary immunodeficiency

    • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

    • Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Iowa City Iowa United States 52242
    2 Research Site Minneapolis Minnesota United States 55426
    3 Research Site Saint Paul Minnesota United States 55101
    4 Research Site Basking Ridge New Jersey United States 07920
    5 Research Site Middletown New Jersey United States 07748
    6 Research Site Montvale New Jersey United States 07645
    7 Research Site Ridgewood New Jersey United States 07450
    8 Research Site Commack New York United States 11725
    9 Research Site Harrison New York United States 10604
    10 Research Site Long Island City New York United States 11101
    11 Research Site New York New York United States 10011
    12 Research Site New York New York United States 10019
    13 Research Site New York New York United States 10029
    14 Research Site New York New York United States 10065
    15 Research Site Uniondale New York United States 11553
    16 Research Site Chapel Hill North Carolina United States 27514
    17 Research Site Portland Oregon United States 97239
    18 Research Site Chattanooga Tennessee United States 37404
    19 Research Site Germantown Tennessee United States 38138
    20 Research Site Fort Worth Texas United States 76104
    21 Research Site East Melbourne Australia 3002
    22 Research Site Westmead Australia 2145
    23 Research Site Anderlecht Belgium 1070
    24 Research Site Antwerpen Belgium 2020
    25 Research Site Edegem Belgium 2650
    26 Research Site Leuven Belgium 3000
    27 Research Site Ottignies Belgium 1340
    28 Research Site Brasília Brazil 70200-730
    29 Research Site Florianópolis Brazil 88034-000
    30 Research Site Goiania Brazil 74605-070
    31 Research Site Porto Alegre Brazil 90035-003
    32 Research Site Porto Alegre Brazil 90110-270
    33 Research Site Sao Paulo Brazil 01317-001
    34 Research Site Sao Paulo Brazil 04543-000
    35 Research Site São Paulo Brazil 03102-002
    36 Research Site São Paulo Brazil 04538-132
    37 Research Site Kelowna British Columbia Canada V1Y 5L3
    38 Research Site Quebec Canada G1J 1Z4
    39 Research Site Villejuif Cedex France 94805
    40 Research Site Seoul Korea, Republic of 03080
    41 Research Site Seoul Korea, Republic of 03722
    42 Research Site Seoul Korea, Republic of 05505
    43 Research Site Seoul Korea, Republic of 06351
    44 Research Site Culiacán Mexico 80230
    45 Research Site La Paz Mexico 23040
    46 Research Site Merida Mexico 97000
    47 Research Site Monterrey Mexico 64710
    48 Research Site Moscow Russian Federation 115478
    49 Research Site Moscow Russian Federation 143442
    50 Research Site Saint Petersburg Russian Federation 194017
    51 Research Site Saint Petersburg Russian Federation 195271
    52 Research Site Saint Petersburg Russian Federation 199226
    53 Research Site Saint-Petersburg Russian Federation 197758
    54 Research Site Kaohsiung Taiwan 82445
    55 Research Site Taichung Taiwan 40443
    56 Research Site Taipei City Taiwan 114
    57 Research Site Taipei Taiwan 100
    58 Research Site Taipei Taiwan 11217
    59 Research Site Taipei Taiwan 235
    60 Research Site Taoyuan Taiwan 333

    Sponsors and Collaborators

    • AstraZeneca
    • Daiichi Sankyo Co., Ltd.
    • Daiichi Sankyo Company, Limited

    Investigators

    • Principal Investigator: Komal Jhaveri, MD, FACP, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT04556773
    Other Study ID Numbers:
    • D967JC00002
    First Posted:
    Sep 21, 2020
    Last Update Posted:
    Aug 24, 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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 24, 2022