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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

Trial Status: Active

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.

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

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Los Angeles
Translational Research In Oncology - US Inc
Status: ACTIVE
Contact: Sara Alsterlind Hurvitz
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Sarah Rosales
Phone: 310-794-7686
Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: ACTIVE
Sacramento
University of California Davis Comprehensive Cancer Center
Status: ACTIVE
San Francisco
UCSF Medical Center-Mission Bay
Status: ACTIVE
Contact: UCSF Clinical Trials
Phone: 877-827-3222

Colorado

Aurora
University of Colorado Hospital
Status: ACTIVE

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: ACTIVE
Tampa
Moffitt Cancer Center
Status: ACTIVE

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: ACTIVE

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: ADMINISTRATIVELY_COMPLETE
Contact: Erin k Conder
Phone: 317-278-4315

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Contact: Rebecca P Colgan
Phone: 913-588-7549

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Nancy S. Tait
Phone: 410-328-3546
Email: ntait@umm.edu

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: ACTIVE
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: ACTIVE

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

New Jersey

New Brunswick
Rutgers Cancer Institute of New Jersey
Status: ACTIVE

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: ACTIVE

Oregon

Portland
OHSU Knight Cancer Institute
Status: ACTIVE

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Ben Taub General Hospital
Status: ACTIVE
M D Anderson Cancer Center
Status: ACTIVE
San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: WITHDRAWN
Contact: Sonia Lisa Creighton
Phone: 210-450-1366

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE

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.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Seagen Inc.

  • Primary ID SGNTUC-016
  • Secondary IDs NCI-2019-03833
  • Clinicaltrials.gov ID NCT03975647