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

Primary Purpose

Metastatic Breast Cancer

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Trastuzumab deruxtecan
Durvalumab
Paclitaxel
Capivasertib
Anastrozole
Fulvestrant
Capecitabine
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Breast Cancer, HER2-negative, HER2-low, Trastuzumab Deruxtecan, T-DXd, DS-8201a, DESTINY-Breast08, Anti-HER2 Antibody Drug Conjugate (ADC), Triple-negative breast cancer (TNBC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Module 1: T-DXd + capecitabine

Module 2: T-DXd + durvalumab + paclitaxel

Module 3: T-DXd + capivasertib

Module 4: T-DXd + anastrozole

Module 5: T-DXd + fulvestrant

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

Occurrence of adverse events (AEs)- Part 1
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 1
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of adverse events (AEs)- Part 2
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 2
Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0

Secondary Outcome Measures

Objective Response Rate (ORR)- Part 2
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
Progression Free Survival (PFS)- Part 2
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
Duration of Response (DoR)- Part 2
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
Overall Survival (OS)- Part 2
OS defined as time from the date of first dose until the date of death by any cause
Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a
Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
Immunogenicity of trastuzumab deruxtecan
Percentage of patients who develop ADA for trastuzumab deruxtecan
Serum Concentration of durvalumab
Determination of durvalumab concentration in serum at different time points after administration
Immunogenicity of durvalumab
Percentage of patients who develop ADAs for durvalumab

Full Information

First Posted
September 15, 2020
Last Updated
October 5, 2023
Sponsor
AstraZeneca
Collaborators
Daiichi Sankyo Co., Ltd., Daiichi Sankyo Company, Limited
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1. Study Identification

Unique Protocol Identification Number
NCT04556773
Brief Title
A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer
Acronym
DB-08
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 17, 2020 (Actual)
Primary Completion Date
August 16, 2023 (Actual)
Study Completion Date
November 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Daiichi Sankyo Co., Ltd., Daiichi Sankyo Company, Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
Breast Cancer, HER2-negative, HER2-low, Trastuzumab Deruxtecan, T-DXd, DS-8201a, DESTINY-Breast08, Anti-HER2 Antibody Drug Conjugate (ADC), Triple-negative breast cancer (TNBC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
139 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Module 1: T-DXd + capecitabine
Arm Type
Experimental
Arm Description
T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use
Arm Title
Module 2: T-DXd + durvalumab + paclitaxel
Arm Type
Experimental
Arm Description
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
Arm Title
Module 3: T-DXd + capivasertib
Arm Type
Experimental
Arm Description
T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use
Arm Title
Module 4: T-DXd + anastrozole
Arm Type
Experimental
Arm Description
T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral
Arm Title
Module 5: T-DXd + fulvestrant
Arm Type
Experimental
Arm Description
T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use
Intervention Type
Drug
Intervention Name(s)
Trastuzumab deruxtecan
Other Intervention Name(s)
DS-8201a, T-DXd
Intervention Description
T-DXd: administered as an IV infusion
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
MEDI4736
Intervention Description
Durvalumab: administered as an IV infusion
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol A
Intervention Description
Paclitaxel: administered as an IV infusion
Intervention Type
Drug
Intervention Name(s)
Capivasertib
Other Intervention Name(s)
AZD5363
Intervention Description
Capivasertib: administered orally
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Other Intervention Name(s)
Anastrozol
Intervention Description
Anastrozole: administered orally
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Intervention Description
Fulvestrant: administered as an IM injection
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine: administered orally
Primary Outcome Measure Information:
Title
Occurrence of adverse events (AEs)- Part 1
Description
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
Time Frame
Up to follow-up period, approximately 24 months
Title
Occurrence of serious adverse events (SAEs)- Part 1
Description
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
Time Frame
Up to follow-up period, approximately 24 months
Title
Occurrence of adverse events (AEs)- Part 2
Description
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
Time Frame
Up to follow-up period, approximately 24 months
Title
Occurrence of serious adverse events (SAEs)- Part 2
Description
Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0
Time Frame
Up to follow-up period, approximately 24 months
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)- Part 2
Description
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
Time Frame
Until progression, assessed up to approximately 24 months
Title
Progression Free Survival (PFS)- Part 2
Description
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
Time Frame
Until progression or death, assessed up to approximately 24 months
Title
Duration of Response (DoR)- Part 2
Description
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
Time Frame
Until progression or death, assessed up to approximately 24 months
Title
Overall Survival (OS)- Part 2
Description
OS defined as time from the date of first dose until the date of death by any cause
Time Frame
Until death, assessed up to approximately 24 months
Title
Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a
Description
Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
Time Frame
While on study drug up to study completion, approximately 24 months
Title
Immunogenicity of trastuzumab deruxtecan
Description
Percentage of patients who develop ADA for trastuzumab deruxtecan
Time Frame
Up to follow-up period, approximately 24 months
Title
Serum Concentration of durvalumab
Description
Determination of durvalumab concentration in serum at different time points after administration
Time Frame
While on study drug up to study completion, approximately 24 months
Title
Immunogenicity of durvalumab
Description
Percentage of patients who develop ADAs for durvalumab
Time Frame
Up to follow-up period, approximately 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Patients must be at least 18 years of age Male or female patients who have pathologically documented breast cancer that: Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Komal Jhaveri, MD, FACP
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Research Site
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Facility Name
Research Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Research Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Research Site
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Research Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Research Site
City
East Melbourne
ZIP/Postal Code
3002
Country
Australia
Facility Name
Research Site
City
Westmead
ZIP/Postal Code
2145
Country
Australia
Facility Name
Research Site
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Research Site
City
Ottignies
ZIP/Postal Code
1340
Country
Belgium
Facility Name
Research Site
City
Goiania
ZIP/Postal Code
74605-070
Country
Brazil
Facility Name
Research Site
City
Porto Alegre
ZIP/Postal Code
90035-003
Country
Brazil
Facility Name
Research Site
City
Porto Alegre
ZIP/Postal Code
90110-270
Country
Brazil
Facility Name
Research Site
City
Sao Paulo
ZIP/Postal Code
04543-000
Country
Brazil
Facility Name
Research Site
City
São Paulo
ZIP/Postal Code
03102-002
Country
Brazil
Facility Name
Research Site
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 5L3
Country
Canada
Facility Name
Research Site
City
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Research Site
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Research Site
City
Monterrey
ZIP/Postal Code
64710
Country
Mexico
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
143442
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
199226
Country
Russian Federation
Facility Name
Research Site
City
Kaohsiung
ZIP/Postal Code
82445
Country
Taiwan
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
40443
Country
Taiwan
Facility Name
Research Site
City
Taipei City
ZIP/Postal Code
114
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
235
Country
Taiwan
Facility Name
Research Site
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
http://BreastCancerStudyLocator.com
Description
AstraZeneca Breast Cancer Study Locator website - To learn which AstraZeneca breast cancer clinical trials are looking for participants with specific diagnosis, stage, and treatment history.

Learn more about this trial

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

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