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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04556773




Registration number
NCT04556773
Ethics application status
Date submitted
15/09/2020
Date registered
21/09/2020

Titles & IDs
Public title
A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer
Scientific 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)
Secondary ID [1] 0 0
2023-505690-33-00
Secondary ID [2] 0 0
D967JC00002
Universal Trial Number (UTN)
Trial acronym
DB-08
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trastuzumab deruxtecan
Treatment: Drugs - Durvalumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Capivasertib
Treatment: Drugs - Anastrozole
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Capecitabine

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

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

Experimental: Module 3: T-DXd + capivasertib - T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use

Experimental: Module 4: T-DXd + anastrozole - T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral

Experimental: Module 5: T-DXd + fulvestrant - T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use


Treatment: Drugs: Trastuzumab deruxtecan
T-DXd: administered as an IV infusion

Treatment: Drugs: Durvalumab
Durvalumab: administered as an IV infusion

Treatment: Drugs: Paclitaxel
Paclitaxel: administered as an IV infusion

Treatment: Drugs: Capivasertib
Capivasertib: administered orally

Treatment: Drugs: Anastrozole
Anastrozole: administered orally

Treatment: Drugs: Fulvestrant
Fulvestrant: administered as an IM injection

Treatment: Drugs: Capecitabine
Capecitabine: administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of adverse events (AEs)- Part 1
Timepoint [1] 0 0
Up to follow-up period, approximately 24 months
Primary outcome [2] 0 0
Occurrence of serious adverse events (SAEs)- Part 1
Timepoint [2] 0 0
Up to follow-up period, approximately 24 months
Primary outcome [3] 0 0
Occurrence of adverse events (AEs)- Part 2
Timepoint [3] 0 0
Up to follow-up period, approximately 24 months
Primary outcome [4] 0 0
Occurrence of serious adverse events (SAEs)- Part 2
Timepoint [4] 0 0
Up to follow-up period, approximately 24 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR)- Part 2
Timepoint [1] 0 0
Until progression, assessed up to approximately 24 months
Secondary outcome [2] 0 0
Progression Free Survival (PFS)- Part 2
Timepoint [2] 0 0
Until progression or death, assessed up to approximately 24 months
Secondary outcome [3] 0 0
Duration of Response (DoR)- Part 2
Timepoint [3] 0 0
Until progression or death, assessed up to approximately 24 months
Secondary outcome [4] 0 0
Overall Survival (OS)- Part 2
Timepoint [4] 0 0
Until death, assessed up to approximately 24 months
Secondary outcome [5] 0 0
Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a
Timepoint [5] 0 0
While on study drug up to study completion, approximately 24 months
Secondary outcome [6] 0 0
Immunogenicity of trastuzumab deruxtecan
Timepoint [6] 0 0
Up to follow-up period, approximately 24 months
Secondary outcome [7] 0 0
Serum Concentration of durvalumab
Timepoint [7] 0 0
While on study drug up to study completion, approximately 24 months
Secondary outcome [8] 0 0
Immunogenicity of durvalumab
Timepoint [8] 0 0
Up to follow-up period, approximately 24 months

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/11/2025
Actual
Sample size
Target
Accrual to date
Final
138
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - East Melbourne
Recruitment hospital [2] 0 0
Research Site - Westmead
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Edegem
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Belgium
State/province [7] 0 0
Ottignies
Country [8] 0 0
Brazil
State/province [8] 0 0
Goiania
Country [9] 0 0
Brazil
State/province [9] 0 0
Porto Alegre
Country [10] 0 0
Brazil
State/province [10] 0 0
Sao Paulo
Country [11] 0 0
Brazil
State/province [11] 0 0
São Paulo
Country [12] 0 0
Canada
State/province [12] 0 0
British Columbia
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Villejuif Cedex
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Mexico
State/province [16] 0 0
Monterrey
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Moscow
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Saint Petersburg
Country [19] 0 0
Taiwan
State/province [19] 0 0
Kaohsiung
Country [20] 0 0
Taiwan
State/province [20] 0 0
Taichung
Country [21] 0 0
Taiwan
State/province [21] 0 0
Taipei City
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taipei
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Daiichi Sankyo Co., Ltd.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Daiichi Sankyo Company, Limited
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Komal Jhaveri, MD, FACP
Address 0 0
Memorial Sloan Kettering Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04556773