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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
Date last updated
25/11/2024

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
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
Trial website
https://clinicaltrials.gov/study/NCT04556773
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04556773