Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03975647




Registration number
NCT03975647
Ethics application status
Date submitted
4/06/2019
Date registered
5/06/2019
Date last updated
18/06/2024

Titles & IDs
Public title
A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer
Scientific title
Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB-02)
Secondary ID [1] 0 0
SGNTUC-016
Universal Trial Number (UTN)
Trial acronym
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 - placebo
Treatment: Drugs - T-DM1

Experimental: Tucatinib + T-DM1 - Tucatinib + T-DM1

Active comparator: Placebo + T-DM1 - Placebo + T-DM1


Treatment: Drugs: tucatinib
300mg given twice per day by mouth (orally)

Treatment: Drugs: placebo
Given twice per day orally

Treatment: Drugs: T-DM1
3.6 mg/kg given into the vein (IV; intravenously) every 21 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
PFS per RECIST v1.1 by blinded independent committee review (BICR)
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [3] 0 0
PFS per RECIST v1.1 by investigator assessment in participants with brain metastases at baseline (PFS.BM per investigator)
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [4] 0 0
PFS.BM per RECIST v1.1 by BICR
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Objective response rate (ORR) per RECIST v1.1 by investigator assessment
Timepoint [5] 0 0
Up to approximately 3 years
Secondary outcome [6] 0 0
ORR per RECIST v1.1 by BICR
Timepoint [6] 0 0
Up to approximately 3 years
Secondary outcome [7] 0 0
Overall survival in participants with brain metastases at baseline (OS.BM)
Timepoint [7] 0 0
Up to approximately 5 years
Secondary outcome [8] 0 0
Duration of response (DOR) per RECIST v1.1 by investigator assessment
Timepoint [8] 0 0
Up to approximately 5 years
Secondary outcome [9] 0 0
DOR per RECIST v1.1 by BICR
Timepoint [9] 0 0
Up to approximately 5 years
Secondary outcome [10] 0 0
Clinical benefit rate (CBR) per RECIST v1.1 by investigator assessment
Timepoint [10] 0 0
Up to approximately 3 years
Secondary outcome [11] 0 0
CBR per RECIST v1.1 by BICR
Timepoint [11] 0 0
Up to approximately 3 years
Secondary outcome [12] 0 0
Number of participants with adverse events (AEs)
Timepoint [12] 0 0
Through 1 month following last dose; up to approximately 9 months overall per participant

Eligibility
Key inclusion criteria
*

* Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory
* History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination
* Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy
* Measurable or non-measurable disease assessable by RECIST v1.1
* ECOG performance status score of 0 or 1
* CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must have at least one of the following:

(a) No evidence of brain metastases

(b) Untreated brain metastases not needing immediate local therapy

(c) Previously treated brain metastases
1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy
2. Participants treated with CNS local therapy for newly identified lesions or previously treated and progressing lesions may be eligible to enroll if all of the following criteria are met:

(i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 14 days prior to first dose, or time since surgical resection is at least 28 days.

(ii) Other sites of evaluable disease are present
3. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
*
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for =21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for =21 days and was discontinued for reasons other than disease progression or severe toxicity).
* CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following:

1. Any untreated brain lesions >2 cm in size
2. Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).
3. Any brain lesion thought to require immediate local therapy
4. Known or concurrent leptomeningeal disease as documented by the investigator
5. Poorly controlled generalized or complex partial seizures

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
2/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2027
Actual
Sample size
Target
565
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
Austin Health - Melbourne
Recruitment hospital [3] 0 0
Breast Cancer Research Centre - Nedlands
Recruitment hospital [4] 0 0
Mater Hospital - Sydney
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3084 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment postcode(s) [4] 0 0
2060 - Sydney
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Hawaii
Country [11] 0 0
United States of America
State/province [11] 0 0
Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Kansas
Country [14] 0 0
United States of America
State/province [14] 0 0
Kentucky
Country [15] 0 0
United States of America
State/province [15] 0 0
Louisiana
Country [16] 0 0
United States of America
State/province [16] 0 0
Maryland
Country [17] 0 0
United States of America
State/province [17] 0 0
Massachusetts
Country [18] 0 0
United States of America
State/province [18] 0 0
Michigan
Country [19] 0 0
United States of America
State/province [19] 0 0
Minnesota
Country [20] 0 0
United States of America
State/province [20] 0 0
Mississippi
Country [21] 0 0
United States of America
State/province [21] 0 0
Missouri
Country [22] 0 0
United States of America
State/province [22] 0 0
Montana
Country [23] 0 0
United States of America
State/province [23] 0 0
Nebraska
Country [24] 0 0
United States of America
State/province [24] 0 0
Nevada
Country [25] 0 0
United States of America
State/province [25] 0 0
New Jersey
Country [26] 0 0
United States of America
State/province [26] 0 0
New York
Country [27] 0 0
United States of America
State/province [27] 0 0
North Carolina
Country [28] 0 0
United States of America
State/province [28] 0 0
Oregon
Country [29] 0 0
United States of America
State/province [29] 0 0
Pennsylvania
Country [30] 0 0
United States of America
State/province [30] 0 0
Tennessee
Country [31] 0 0
United States of America
State/province [31] 0 0
Texas
Country [32] 0 0
United States of America
State/province [32] 0 0
Utah
Country [33] 0 0
United States of America
State/province [33] 0 0
Virginia
Country [34] 0 0
United States of America
State/province [34] 0 0
Washington
Country [35] 0 0
Austria
State/province [35] 0 0
Other
Country [36] 0 0
Belgium
State/province [36] 0 0
Other
Country [37] 0 0
Canada
State/province [37] 0 0
Alberta
Country [38] 0 0
Canada
State/province [38] 0 0
Nova Scotia
Country [39] 0 0
Canada
State/province [39] 0 0
Ontario
Country [40] 0 0
Canada
State/province [40] 0 0
Quebec
Country [41] 0 0
Canada
State/province [41] 0 0
Saskatchewan
Country [42] 0 0
China
State/province [42] 0 0
Other
Country [43] 0 0
China
State/province [43] 0 0
Bejing
Country [44] 0 0
China
State/province [44] 0 0
Guangzhou
Country [45] 0 0
China
State/province [45] 0 0
Nanchang City
Country [46] 0 0
China
State/province [46] 0 0
Nanning
Country [47] 0 0
Denmark
State/province [47] 0 0
Other
Country [48] 0 0
France
State/province [48] 0 0
Other
Country [49] 0 0
Germany
State/province [49] 0 0
Other
Country [50] 0 0
Israel
State/province [50] 0 0
Other
Country [51] 0 0
Italy
State/province [51] 0 0
Other
Country [52] 0 0
Japan
State/province [52] 0 0
Other
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Other
Country [54] 0 0
Netherlands
State/province [54] 0 0
Other
Country [55] 0 0
Singapore
State/province [55] 0 0
Other
Country [56] 0 0
Spain
State/province [56] 0 0
Other
Country [57] 0 0
Sweden
State/province [57] 0 0
Other
Country [58] 0 0
Switzerland
State/province [58] 0 0
Other
Country [59] 0 0
Taiwan
State/province [59] 0 0
Other
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Other

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery.

Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer.

Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.
Trial website
https://clinicaltrials.gov/study/NCT03975647
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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03975647