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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05132582




Registration number
NCT05132582
Ethics application status
Date submitted
12/11/2021
Date registered
24/11/2021
Date last updated
25/06/2024

Titles & IDs
Public title
A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer
Scientific title
A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)
Secondary ID [1] 0 0
SGNTUC-028
Universal Trial Number (UTN)
Trial acronym
HER2CLIMB-05
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2 Positive 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 - Tucatinib
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Pertuzumab
Treatment: Drugs - Combination product: Trastuzumab + Pertuzumab
Treatment: Drugs - Placebo

Experimental: Tucatinib + trastuzumab + pertuzumab - Tucatinib + trastuzumab + pertuzumab

Active comparator: Placebo + trastuzumab + pertuzumab - Placebo + trastuzumab + pertuzumab


Treatment: Drugs: Tucatinib
300mg given by mouth (orally) twice daily

Treatment: Drugs: Trastuzumab
6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days

Treatment: Drugs: Pertuzumab
420mg given by IV every 21 days

Treatment: Drugs: Combination product: Trastuzumab + Pertuzumab
600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually.

Treatment: Drugs: Placebo
Given orally twice daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
PFS by blinded independent central review (BICR) per RECIST v1.1
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
Time to deterioration of health-related quality of life (HRQoL)
Timepoint [3] 0 0
Up to approximately 3 years
Secondary outcome [4] 0 0
Central nervous system (CNS) PFS
Timepoint [4] 0 0
Up to approximately 3 years
Secondary outcome [5] 0 0
Incidence of adverse events (AEs)
Timepoint [5] 0 0
Through 30 days after last study treatment, approximately 18 months
Secondary outcome [6] 0 0
Incidence of laboratory abnormalities
Timepoint [6] 0 0
Through 30 days after last study treatment, approximately 18 months
Secondary outcome [7] 0 0
Incidence of tucatinib dose alterations
Timepoint [7] 0 0
Through 30 days after last study treatment, approximately 18 months
Secondary outcome [8] 0 0
Incidence of trastuzumab dose alterations
Timepoint [8] 0 0
Through 30 days after last study treatment, approximately 18 months
Secondary outcome [9] 0 0
Incidence of pertuzumab dose alterations
Timepoint [9] 0 0
Through 30 days after last study treatment, approximately 18 months
Secondary outcome [10] 0 0
Maximum concentration (Cmax)
Timepoint [10] 0 0
Through 30 days after last study treatment, approximately 18 months
Secondary outcome [11] 0 0
Trough concentration (Ctrough)
Timepoint [11] 0 0
Through 30 days after last study treatment, approximately 18 months

Eligibility
Key inclusion criteria
* Centrally confirmed HER2+ breast carcinoma according to the 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines prior to randomization (defined as a 3+ score on immunohistochemistry (IHC) and/or 2+ IHC and concurrent positive by ISH).
* Have unresectable locally advanced or metastatic disease.

* If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab and pertuzumab received in the early breast cancer setting for advanced HER2+ disease.
* Have received 4-8 cycles of pre-study induction therapy including only trastuzumab, pertuzumab, and taxane as first-line of therapy for the treatment of advanced breast cancer prior to study enrollment. Participants are eligible provided they are without evidence of disease progression following completion of induction therapy.
* Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-])
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* CNS Inclusion - Based on screening contrast-enhanced brain magnetic resonance imaging (MRI), participants may have any of the following:

* No evidence of brain metastases
* Untreated brain metastases which are asymptomatic not needing immediate local treatment and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane
* Previously treated brain metastases which are asymptomatic

* Brain metastases previously treated with local therapy must not have progressed since treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with any tyrosine kinase inhibitor targeting HER2 and/or epidermal growth factor receptor (EGFR) including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and = 12 months have elapsed since last neratinib dose prior to start of study drug)
* Unable to undergo contrast-enhanced MRI of the brain
* CNS Exclusion - Based on screening brain MRI and clinical assessment

* Symptomatic brain metastasis after CNS-directed local therapy
* Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane
* Ongoing use of systemic corticosteroids at a total daily dose of >2 mg of dexamethasone (or equivalent)
* Any untreated brain lesion in an anatomic site which may pose risk to participant
* Known or suspected leptomeningeal disease (LMD)
* Poorly controlled (>1/week) seizures, or other persistent neurologic symptoms

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2027
Actual
Sample size
Target
650
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
Cancer Research South Australia - Adelaide
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [5] 0 0
Peninsula and South East Oncology - Frankston
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Macquarie University Hospital - Macquarie University
Recruitment hospital [8] 0 0
St John of God Subiaco Hospital - Subiaco
Recruitment hospital [9] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
2050 - Camperdown
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
2109 - Macquarie University
Recruitment postcode(s) [8] 0 0
6008 - Subiaco
Recruitment postcode(s) [9] 0 0
2145 - Sydney
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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California
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Illinois
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Nebraska
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New York
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Ohio
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Pennsylvania
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South Carolina
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Tennessee
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Washington
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Wisconsin
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Austria
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Belgium
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Canada
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Ontario
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Canada
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Quebec
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Chile
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China
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China
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Nanchang City
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China
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Nanning
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Czechia
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France
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France
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Paris
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Germany
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Germany
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Regensburg
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Greece
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Italy
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Seoul
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Netherlands
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Portugal
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Spain
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Switzerland
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Taiwan
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Taipei
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.

Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).

In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in.

All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.
Trial website
https://clinicaltrials.gov/study/NCT05132582
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Seagen Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Seagen Trial Information Support
Address 0 0
Country 0 0
Phone 0 0
866-333-7436
Fax 0 0
Email 0 0
clinicaltrials@seagen.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05132582