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A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+
Breast Cancer

  ClinicalTrials.gov Identifier: NCT03975647

The safety and scientific validity of this study is the responsibility of the
Recruitment Status  : Recruiting
study sponsor and investigators. Listing a study does not mean it has
First Posted  : June 5, 2019
been evaluated by the U.S. Federal Government.
Know the risks and
Last Update Posted  : July 13, 2021
potential benefits of clinical studies and talk to your health care provider
before participating.
Read our disclaimer for details. See Contacts and Locations

Sponsor:
Seagen Inc.

Information provided by (Responsible Party):

Seagen Inc.

Study Details Tabular View No Results Posted Disclaimer How to Read a Study Record

Study Description Go to 

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.

Condition or disease  Intervention/treatment  Phase 

HER2-positive Breast Cancer Drug: tucatinib Phase 3

Drug: placebo

Drug: T-DM1

Detailed Description:

This study is designed to evaluate the efficacy and safety of tucatinib in combination with T-DM1 in subjects with unresectable locally-advanced or metastatic HER2+ breast cancer who
have had prior treatment with a taxane and trastuzumab in any setting. Prior pertuzumab treatment is permitted, but not required. Subjects will be randomized in a 1:1 manner to receive
21-day cycles of either tucatinib or placebo in combination with T-DM1.

While on study treatment, subjects will be assessed for progression every 6 weeks for the first 24 weeks, and every 9 weeks thereafter, irrespective of dose holds or interruptions. Study
treatment will continue until unacceptable toxicity, disease progression, withdrawal of consent, or study closure. After completion of study treatment and after occurrence of disease
progression, subjects in both arms of the study will continue to be followed for survival until study closure or withdrawal of consent.

Study Design Go to 

Study Type  : Interventional

 (Clinical Trial)
Estimated
Enrollment  : 460 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date  : October 2, 2019
Estimated Primary Completion Date  : April 30, 2024
Estimated Study Completion Date  : April 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics:

Breast cancer

MedlinePlus related topics:

Breast Cancer

Drug Information available for:

Trastuzumab
Tucatinib
Trastuzumab emtansine

U.S. FDA Resources

Arms and Interventions Go to 

Arm  Intervention/treatment 

Experimental: Tucatinib + T-DM1 Drug: tucatinib

Tucatinib + T-DM1 300mg given twice per day by mouth (orally)
Other Name: ONT-380

Drug: T-DM1
3.6 mg/kg given into the vein (IV; intravenously) every 21 days
Other Name: Kadcyla

Active Comparator: Placebo + T-DM1 Drug: placebo

Placebo + T-DM1 Given twice per day orally

Drug: T-DM1
3.6 mg/kg given into the vein (IV; intravenously) every 21 days
Other Name: Kadcyla

Outcome Measures Go to 

Primary Outcome Measures  :

1. Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment [ Time Frame: Up to approximately 5 years ]

PFS per investigator is defined as the time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any
cause, whichever occurs first.

Secondary Outcome Measures  :

1. Overall Survival [ Time Frame: Up to approximately 5 years ]

OS is defined as the time from randomization to death due to any cause.

2. PFS per RECIST v1.1 by blinded independent committee review (BICR) [ Time Frame: Up to approximately 5 years ]

PFS per BICR is defined as the time from the date of randomization to the centrally-reviewed documented disease progression according to RECIST v1.1 or death from any
cause, whichever occurs first.

3. PFS per RECIST v1.1 by investigator assessment in participants with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]

4. PFS per RECIST v1.1 by BICR in patients with brain metastases at baseline [ Time Frame: Up to approximately 5 years ]

5. Objective response rate (ORR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]

ORR is defined as the proportion of subjects with complete response (CR) or partial response (PR) according to RECIST v1.1.

6. ORR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]

7. Duration of response (DOR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 5 years ]

DOR is defined as the time from first documentation of objective response to the first documentation of disease progression or death from any cause, whichever occurs earlier.

8. DOR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 5 years ]

9. Clinical benefit rate (CBR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]

CBR is defined as the proportion of subjects with stable disease (SD) or non-CR or non-PD for ≥6 months or best response of CR or PR according to RECIST v1.1.

10. CBR per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]

11. Number of participants with adverse events (AEs) [ Time Frame: Through 1 month following last dose; up to approximately 9 months overall per participant ]

An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal
relationship with this treatment.

Eligibility Criteria Go to 

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a
study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general
information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Criteria

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), subjects 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. Subjects 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 21 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

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), subjects 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

Contacts and Locations Go to 

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03975647

Contacts

Contact: Seagen Trial Information Support 866-333-7436 [email protected]

Locations

Show 215 study locations

Sponsors and Collaborators

Seagen Inc.

Investigators

Study Director: Evelyn Rustia, MD Seagen Inc.

More Information Go to 

Responsible Party: Seagen Inc.

ClinicalTrials.gov Identifier: NCT03975647    
History of Changes
Other Study ID Numbers: SGNTUC-016

First Posted: June 5, 2019

  
Key Record Dates
Last Update Posted: July 13, 2021
Last Verified: July 2021

Studies a U.S. FDA-regulated Drug Product: Yes

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Seagen Inc.:

Seattle Genetics

Additional relevant MeSH terms:

Breast Neoplasms
Antineoplastic Agents, Immunological

Neoplasms by Site
Antineoplastic Agents

Neoplasms
Tubulin Modulators
Breast Diseases
Antimitotic Agents

Skin Diseases
Mitosis Modulators

Ado-trastuzumab emtansine
Molecular Mechanisms of Pharmacological Action

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