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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04538742




Registration number
NCT04538742
Ethics application status
Date submitted
31/08/2020
Date registered
4/09/2020

Titles & IDs
Public title
A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer
Scientific 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)
Secondary ID [1] 0 0
2019-004531-22
Secondary ID [2] 0 0
D967JC00001
Universal Trial Number (UTN)
Trial acronym
DB-07
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 - Pertuzumab
Treatment: Drugs - Tucatinib

Experimental: Module 1- T-DXd and Durvalumab - T-DXd and Durvalumab

Experimental: Module 2- T-DXd and Pertuzumab - T-DXd and Pertuzumab

Experimental: Module 3- T-DXd and Paclitaxel - T-DXd and Paclitaxel (Arm not initiated in Part 2)

Experimental: Module 4- T-DXd and Durvalumab and Paclitaxel - T-DXd and Durvalumab and Paclitaxel (Arm not initiated in Part 1 and Part 2)

Experimental: Module 0- T-DXd - T-DXd

Experimental: Module 5 - T-DXd and Tucatanib - T-DXd and tucatinib (Arm not initiated in Part 2)

Experimental: Module 6 - T-DXd and Tucatinib - T-DXd and tucatinib in patients with active brain metastases (Part 2 Only) (Arm not initiated)

Experimental: Module 7 - T-DXd - T-DXd monotherapy in patients with active brain metastases (Part 2 Only)


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: Pertuzumab
Pertuzumab: administered as an IV infusion

Treatment: Drugs: Tucatinib
Tucatinib administered orally (tablet) twice daily

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 53 months
Primary outcome [2] 0 0
Occurrence of serious adverse events (SAEs)- Part 1
Timepoint [2] 0 0
Up to follow-up period, approximately 53 months
Primary outcome [3] 0 0
Occurrence of adverse events (AEs)- Part 2
Timepoint [3] 0 0
Up to follow-up period, approximately 53 months
Primary outcome [4] 0 0
Occurrence of serious adverse events (SAEs)- Part 2
Timepoint [4] 0 0
Up to follow-up period, approximately 53 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR)- Part 1 and Part 2
Timepoint [1] 0 0
Until progression, assessed up to approximately 53 months
Secondary outcome [2] 0 0
Progression Free Survival (PFS)- Part 1 and Part 2
Timepoint [2] 0 0
Until progression, assessed up to approximately 53 months
Secondary outcome [3] 0 0
Progression Free Survival 2 (PFS2)- Part 2
Timepoint [3] 0 0
Assessed up to approximately 53 months
Secondary outcome [4] 0 0
Duration of Response (DoR)- Part 2
Timepoint [4] 0 0
Until progression, assessed up to approximately 53 months
Secondary outcome [5] 0 0
Overall Survival (OS)- Part 2
Timepoint [5] 0 0
Until death, assessed up to approximately 53 months
Secondary outcome [6] 0 0
Serum Concentration of Trastuzumab Deruxtecan (T-DXd)
Timepoint [6] 0 0
While on study drug up to study completion, approximately 53 months
Secondary outcome [7] 0 0
Serum Concentration of Durvalumab
Timepoint [7] 0 0
While on study drug up to study completion, approximately 53 months
Secondary outcome [8] 0 0
Serum Concentration of Pertuzumab
Timepoint [8] 0 0
While on study drug up to study completion, approximately 53 months
Secondary outcome [9] 0 0
Plasma Concentration of Paclitaxel
Timepoint [9] 0 0
While on study drug up to study completion, approximately 53 months
Secondary outcome [10] 0 0
Plasma Concentration of Tucatinib
Timepoint [10] 0 0
While on study drug up to study completion, approximately 53 months
Secondary outcome [11] 0 0
Immunogenicity of trastuzumab deruxtecan
Timepoint [11] 0 0
Up to follow-up period, approximately 53 months
Secondary outcome [12] 0 0
Immunogenicity of Durvalumab
Timepoint [12] 0 0
Up to follow-up period, approximately 53 months
Secondary outcome [13] 0 0
Immunogenicity of Pertuzumab
Timepoint [13] 0 0
Up to follow-up period, approximately 53 months

Eligibility
Key inclusion criteria
Key

* 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)

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Other
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
Brazil
State/province [7] 0 0
Barretos
Country [8] 0 0
Brazil
State/province [8] 0 0
Belo Horizonte
Country [9] 0 0
Brazil
State/province [9] 0 0
Natal
Country [10] 0 0
Brazil
State/province [10] 0 0
Porto Alegre
Country [11] 0 0
Brazil
State/province [11] 0 0
Rio de Janeiro
Country [12] 0 0
Brazil
State/province [12] 0 0
Sao Paulo
Country [13] 0 0
Brazil
State/province [13] 0 0
Sorocaba
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Canada
State/province [15] 0 0
Toronto
Country [16] 0 0
France
State/province [16] 0 0
Villejuif Cedex
Country [17] 0 0
Germany
State/province [17] 0 0
München
Country [18] 0 0
Germany
State/province [18] 0 0
Würzburg
Country [19] 0 0
India
State/province [19] 0 0
Delhi
Country [20] 0 0
India
State/province [20] 0 0
Gurgaon
Country [21] 0 0
India
State/province [21] 0 0
Madurai
Country [22] 0 0
India
State/province [22] 0 0
Mumbai
Country [23] 0 0
Italy
State/province [23] 0 0
Bologna
Country [24] 0 0
Italy
State/province [24] 0 0
Milan
Country [25] 0 0
Italy
State/province [25] 0 0
Napoli
Country [26] 0 0
Italy
State/province [26] 0 0
Rome
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Busan-si
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Poland
State/province [29] 0 0
Bydgoszcz
Country [30] 0 0
Poland
State/province [30] 0 0
Koszalin
Country [31] 0 0
Poland
State/province [31] 0 0
Lublin
Country [32] 0 0
Poland
State/province [32] 0 0
Lódz
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Moscow
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Saint Petersburg
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Sankt-Peterburg
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
L'Hospitalet de Llobregat
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Sevilla
Country [40] 0 0
Taiwan
State/province [40] 0 0
Hualien
Country [41] 0 0
Taiwan
State/province [41] 0 0
Tainan
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei City
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taoyuan City
Country [45] 0 0
Turkey
State/province [45] 0 0
Ankara
Country [46] 0 0
Turkey
State/province [46] 0 0
Edirne
Country [47] 0 0
Turkey
State/province [47] 0 0
Istanbul
Country [48] 0 0
Turkey
State/province [48] 0 0
Izmir
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Buckhurst Hill

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Address 0 0
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.