A Study of Tucatinib Plus Trastuzumab Deruxtecan in HER2+ Breast Cancer (HER2CLIMB-04)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HER2 Positive Breast Cancer
• Intervention / Treatment: Drug: tucatinib; Drug: trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Seagen Trial Information Support; Phone Number: 866-333-7436; Email: clinicaltrials@seagen.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates, PC - HOPE
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope
    • Los Angeles, California, United States, 90095
      • UCLA Department of Medicine - Hematology & Oncology
    • San Francisco, California, United States, 94158
      • University of California at San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045-0510
      • University of Colorado Hospital / University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center / Georgetown University Medical Center
  • Florida
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - North Region
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute / Emory University School of Medicine
    • Sandy Springs, Georgia, United States, 30341
      • Georgia Cancer Specialists / Northside Hospital Cancer Institute
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center / University of Louisville
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health Cancer Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Health Kansas City
    • Kansas City, Missouri, United States, 64113
      • Saint Luke's Cancer Institute LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center / University of North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center / Wake Forest University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Tigard, Oregon, United States, 97223
      • Northwest Cancer Specialists, P.C.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens Hospital of UPMC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology and Hematology Associates/Tennessee Oncology-Memorial Plaza
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology-Nashville/Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75231
      • Texas Oncology - DFW
    • Houston, Texas, United States, 77030-4095
      • MD Anderson Cancer Center / University of Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Salem, Virginia, United States, 24153
      • Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance / University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Carbone Cancer Center / University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Tucatinib + trastuzumab deruxtecan	Drug: tucatinib; 300 mg orally twice daily; Other Names: TUKYSA, ARRY-380, ONT-380; Drug: trastuzumab deruxtecan; 5.4 mg/kg via intravenous (into the vein; IV) infusion on Day 1 of each of 21-day cycle; Other Names: T-DXd, Enhertu, DS-8201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed objective response rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 according to investigator assessment	ORR is defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR) per RECIST v1.1	From start of treatment up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR) per RECIST v1.1 according to investigator assessment	DOR is defined as the time from first documentation of objective response to the first documentation of disease progression per RECIST v1.1 or death from any cause, whichever occurs earlier	From start of treatment up to approximately 3 years
Progression-free survival (PFS) per RECIST v1.1 according to investigator assessment	PFS is defined as the time from start of study treatment to first documentation of tumor progression or to death due to any cause, whichever comes first	From start of treatment up to approximately 3 years
Disease control rate (DCR) per RECIST v1.1 according to investigator assessment	DCR is defined as the proportion of subjects with confirmed CR, PR or stable disease according to RECIST v1.1	From start of treatment up to approximately 3 years
Overall survival (OS)	OS is defined as the time from treatment initiation to death due to any cause	From start of treatment up to approximately 5 years
Incidence of adverse events (AEs)	An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	From start of treatment up to approximately 3 years
Incidence of laboratory abnormalities		From start of treatment up to approximately 3 years
Incidence of dose modifications		From start of treatment up to approximately 3 years
Incidence of treatment discontinuations		From start of treatment up to approximately 3 years

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Jorge Ramos, DO, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: August 31, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic breast cancer; Seattle Genetics; HER2+ breast cancer; Stage IV breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immunoconjugates; Trastuzumab; Tucatinib; Trastuzumab deruxtecan
• Other Study ID Numbers: SGNTUC-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No