Clinical trial NCT04539938: A Study of Tucatinib Plus Trastuzumab Deruxtecan in HER2+ Breast Cancer
Official title: A Single Arm, Open Label Phase 2 Study of Tucatinib in Combination With Trastuzumab Deruxtecan in Subjects With Previously Treated Unresectable Locally-Advanced or Metastatic HER2+ Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HER2 Positive Breast Cancer
Keywords: HER2+ breast cancer
Metastatic breast cancer
Stage IV breast cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-07
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial studies how well the drug tucatinib works when given with trastuzumab deruxtecan (T-DXd). It will also look at what side effects happen when these drugs are given together. A side effect is anything a drug does besides treating cancer.

Participants in this trial have HER2-positive (HER2+) breast cancer that has either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable). All participants will get both tucatinib and T-DXd.


Eligibility criteria: Inclusion Criteria

* Have confirmed HER2+ breast cancer, as defined by the current American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines, previously determined at a Clinical Laboratory Improvements Amendments (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory.
* History of prior treatment with a taxane and trastuzumab in the LA/M setting OR progressed within 6 months after neoadjuvant or adjuvant treatment, including a taxane and trastuzumab.
* Have progression of unresectable LA/M breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy
* Have measurable disease assessable by RECIST v1.1
* Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
* Have a life expectancy of at least 6 months, in the opinion of the investigator
* CNS Inclusion - Based on medical history and screening contrast brain magnetic resonance imaging (MRI), participants with a history of brain metastases must have one of the following:

  * Untreated brain metastases not needing immediate local therapy. For participants with untreated central nervous system (CNS) lesions \>2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment
  * 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 in the opinion of the investigator
    * Participants treated with CNS local therapy for newly identified or previously treated progressing lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if all of the following criteria are met:

      * Time since whole brain radiation therapy (WBRT) is ≥14 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥7 days prior to first dose of study treatment, or time since surgical resection is ≥28 days
      * Other sites of measurable disease by RECIST v1.1 are present
    * Relevant records of any CNS treatment must be available

Exclusion Criteria

* Have previously been treated with:

  * Lapatinib or neratinib within 12 months of starting study treatment (except in cases where lapatinib or neratinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity)
  * Tucatinib or enrolled on a tucatinib clinical trial
  * Any investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) (eg, afatinib) at any time previously
  * Trastuzumab deruxtecan or another antibody-drug conjugate (ADC) consisting of an exatecan derivative
* Have received treatment with:

  * Any systemic anti-cancer therapy (including hormonal therapy) or experimental agent ≤21 days of first dose of study treatment or are currently participating in another interventional clinical trial. An exception for the washout of hormonal therapies is gonadotropin releasing hormone (GnRH) agonists used for ovarian suppression in premenopausal women, which are permitted concomitant medications
  * Treatment with non-CNS radiation ≤7 days prior to first dose of study treatment
  * Major surgery \<28 days of first dose of study treatment
* Have clinically significant cardiopulmonary disease (such as history of iterstitial lung disease (ILD)/pneumonitis that required systemic corticosteroids, or have current ILD/pneumonitis, or where suspected ILD /pneumonitis cannot be ruled out be imaging at screening)
* Have known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment
* Known to be positive for hepatitis B by surface antigen expression. Known to be positive for hepatitis C infection. Participants who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks
* Presence of known chronic liver disease
* Active or uncontrolled clinically serious infection
* Have inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medications

Primary outcomes:
measure: Confirmed objective response rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 according to investigator assessment
timeFrame: From start of treatment up to approximately 3 years
Secondary outcomes:
measure: Duration of response (DOR) per RECIST v1.1 according to investigator assessment
timeFrame: From start of treatment up to approximately 3 years
measure: Progression-free survival (PFS) per RECIST v1.1 according to investigator assessment
timeFrame: From start of treatment up to approximately 3 years
measure: Disease control rate (DCR) per RECIST v1.1 according to investigator assessment
timeFrame: From start of treatment up to approximately 3 years
measure: Overall survival (OS)
timeFrame: From start of treatment up to approximately 5 years
measure: Incidence of adverse events (AEs)
timeFrame: From start of treatment up to approximately 3 years
measure: Incidence of laboratory abnormalities
timeFrame: From start of treatment up to approximately 3 years
measure: Incidence of dose modifications
timeFrame: From start of treatment up to approximately 3 years
measure: Incidence of treatment discontinuations
timeFrame: From start of treatment up to approximately 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine - Hematology & Oncology
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital / University of Colorado
state: Colorado
city: Washington
country: United States
facility: Lombardi Cancer Center / Georgetown University Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Region
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Sandy Springs
country: United States
facility: Georgia Cancer Specialists / Northside Hospital Cancer Institute
state: Georgia
city: Louisville
country: United States
facility: James Graham Brown Cancer Center / University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute LLC
state: Missouri
city: Kansas City
country: United States
facility: HCA Midwest Health Kansas City
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center / University of North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center / Wake Forest University
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Tigard
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Pittsburgh
country: United States
facility: Magee Womens Hospital of UPMC
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Associates/Tennessee Oncology-Memorial Plaza
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - DFW
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: