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: Completed
• 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 Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham, IDS Pharmacy
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates, PC - HOPE
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates, PC - HOPE
  • California
    • Alhambra, California, United States, 91801
      • UCLA Hematology/Oncology - Alhambra
    • Burbank, California, United States, 91505
      • UCLA Hematology/Oncology - Burbank
    • Duarte, California, United States, 91010
      • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Duarte, California, United States, 91010
      • City of Hope Investigational Drug Services (IDS)
    • Laguna Hills, California, United States, 92653
      • UCLA Hematology/Oncology - Laguna Hills
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology
    • Los Angeles, California, United States, 90095
      • (IRB# 20-001502) Ronald Reagan UCLA Medical Center, Drug Information Center
    • Pasadena, California, United States, 91105
      • UCLA Hematology/Oncology - Pasadena
    • San Francisco, California, United States, 94158
      • University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital- Breast Clinic
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital- Oncology Clinic
    • San Luis Obispo, California, United States, 93401
      • UCLA Hematology/Oncology - San Luis Obispo
    • Santa Barbara, California, United States, 93105
      • UCLA Hematology/Oncology - Santa Barbara
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology Parkside
    • Ventura, California, United States, 93003
      • UCLA Hematology/Oncology - Ventura
    • Westlake Village, California, United States, 91361
      • UCLA Hematology/Oncology - Westlake
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver CTO/CTRC - Outpatient.
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
    • Lone Tree, Colorado, United States, 80124
      • UC Health Lone Tree Medical Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University Medical Center
    • Washington D.C., District of Columbia, United States, 20010
      • Washington Cancer Institute at MedStar Washington Hospital Center
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Cancer Specialists
    • Brandon, Florida, United States, 33511
      • Florida Cancer Specialists
    • Clearwater, Florida, United States, 33761
      • Florida Cancer Specialists
    • Gainesville, Florida, United States, 32605
      • Florida Cancer Specialists
    • Largo, Florida, United States, 33770
      • Florida Cancer Specialists
    • Lecanto, Florida, United States, 34461
      • Florida Cancer Specialists
    • Ocala, Florida, United States, 34474
      • Florida Cancer Specialists
    • Orange City, Florida, United States, 32763
      • Florida Cancer Specialists
    • Orlando, Florida, United States, 32806
      • Florida Cancer Specialists
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33607
      • Florida Cancer Specialists
    • Tavares, Florida, United States, 32778
      • Florida Cancer Specialists
    • The Villages, Florida, United States, 32159
      • Florida Cancer Specialists
    • Trinity, Florida, United States, 34655
      • Florida Cancer Specialists
    • Winter Park, Florida, United States, 32789
      • Florida Cancer Specialists
  • Georgia
    • Athens, Georgia, United States, 30606
      • Northside Hospital, Inc - GCS/Athens
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
    • Atlanta, Georgia, United States, 30308
      • Winship Cancer Institute @ Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30342
      • Atlanta Cancer Care - Atlanta
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital, Inc. - Central Research Department
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute / Emory University School of Medicine
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital, Inc. - GCS/Center Pointe
    • Blairsville, Georgia, United States, 30512
      • Northside Hospital, Inc - GCS/Blairsville
    • Canton, Georgia, United States, 30114
      • Northside Hospital, Inc - GCS/Canton
    • Cumming, Georgia, United States, 30041
      • Atlanta Cancer Care - Cumming
    • Decatur, Georgia, United States, 30033
      • Northside Hospital, Inc. - GCS/Decatur
    • Duluth, Georgia, United States, 30096
      • NHCI Suburban Hematology-oncology Associates - Duluth
    • Lawrenceville, Georgia, United States, 30046
      • NHCI Suburban Hematology-oncology Associates - lawrenceville
    • Macon, Georgia, United States, 31217
      • Northside Hospital, Inc - GCS/Macon
    • Marietta, Georgia, United States, 30060
      • Northside Hospital, Inc. - GCS/Marietta
    • Stockbridge, Georgia, United States, 30281
      • Atlanta Cancer Care - Stockbridge
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Harry and Jeanette Weinberg Cancer Institute at Franklin Square
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Newton, Massachusetts, United States, 02459
      • Dana Farber Cancer Institute- Chestnut Hill
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Minnesota Oncology Hematology, PA
    • Fridley, Minnesota, United States, 55432
      • Mercy Hospital - Unity Campus
    • Fridley, Minnesota, United States, 55433
      • Minnesota Oncology Hematology, PA
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, PA
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health Cancer institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Saint Paul, Minnesota, United States, 55102
      • Minnesota Oncology Hematology PA
    • Saint Paul, Minnesota, United States, 55102
      • Minnesota Oncology Hematology, PA
    • Saint Paul, Minnesota, United States, 55102
      • Allina Health Cancer institute
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68114
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68124
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
    • Papillion, Nebraska, United States, 68046
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • MSK Basking Ridge
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Middletown, New Jersey, United States, 07748
      • MSK Monmouth
    • Montvale, New Jersey, United States, 07645
      • MSK Bergen
  • New York
    • Commack, New York, United States, 11725
      • MSK Commack
    • Harrison, New York, United States, 10604
      • MSK Westchester
    • Long Island City, New York, United States, 11101
      • Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy
    • New York, New York, United States, 10065
      • Evelyn H. Lauder Breast and Imaging Center (BAIC).
    • Uniondale, New York, United States, 11553
      • MSK Nassau
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Clinic
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • UPMC Hillman Cancer Center Passavant North
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Hillman Cancer Center Mountainview
    • Monroeville, Pennsylvania, United States, 15146
      • UPMC Hillman Cancer Center UPMC East
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital of UPMC
    • Pittsburgh, Pennsylvania, United States, 15102
      • UPMC Hillman Cancer Center Upper Saint Clair
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC Hillman Cancer Center UPMC Passavant
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute Investigational Drug Service UPMC Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Centers William M. Cooper Ambulatory Care Pavilion of the Hillman Cancer Center
    • Uniontown, Pennsylvania, United States, 15401
      • UPMC Hillman Cancer Center Uniontown
    • Washington, Pennsylvania, United States, 15301
      • UPMC Hillman Cancer Center Washington
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology, PLLC
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Research Institute
    • Chattanooga, Tennessee, United States, 37403
      • Tennessee Oncology, PLLC
    • Cleveland, Tennessee, United States, 37311
      • Tennessee Oncology, PLLC
    • Dickson, Tennessee, United States, 37055
      • Tennessee Oncology, PLLC
    • Franklin, Tennessee, United States, 37067
      • Tennessee Oncology, PLLC
    • Gallatin, Tennessee, United States, 37066
      • Tennessee Oncology, PLLC
    • Hendersonville, Tennessee, United States, 37075
      • Tennessee Oncology, PLLC
    • Hermitage, Tennessee, United States, 37076
      • Tennessee Oncology, PLLC
    • Lebanon, Tennessee, United States, 37909
      • Tennessee Oncology, PLLC
    • Murfreesboro, Tennessee, United States, 37129
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37205
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37207
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37211
      • Tennessee Oncology, PLLC
    • Shelbyville, Tennessee, United States, 37160
      • Tennessee Oncology, PLLC
    • Smyrna, Tennessee, United States, 37167
      • Tennessee Oncology, PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas M.D. Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • U.T. MD Anderson Cancer Center
    • Irving, Texas, United States, 75063
      • US Oncology Investigational Products Center (IPC)
    • Irving, Texas, United States, 75063
      • US Oncology Investigational Product Center (IPC)
    • Irving, Texas, United States, 75063
      • US Oncology lnvestigational Products Center (IPC)
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Gainesville, Virginia, United States, 20155
      • Virginia Cancer Specialists, PC
    • Leesburg, Virginia, United States, 20176
      • Virginia Cancer Specialists, PC
    • Low Moor, Virginia, United States, 24457
      • Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
    • Reston, Virginia, United States, 20190
      • Virginia Cancer Specialists, PC
    • Roanoke, Virginia, United States, 24014
      • Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
    • Salem, Virginia, United States, 24153
      • Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
    • Wytheville, Virginia, United States, 24382
      • Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Clinical Science Center
    • Madison, Wisconsin, United States, 53715
      • UW Health Oncology - One South Park

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; PF-07265792; 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 (INV) Assessment	Confirmed objective response rate was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per investigator according to RECIST v1.1. For a response to be considered confirmed, the subsequent response had to be at least 4 weeks after the initial response. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR: a greater than equal to (>=) 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. 95% exact confidence interval (CI) was based on Clopper-Pearson method.	From the first dose of study treatment until the first documented PD or before start of any new anti-cancer therapy (up to 43 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) Per RECIST v1.1 According to INV	PFS as per INV was defined as the time from the start of the study treatment to the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Kaplan-Meier methods was used for analysis.	From the start of study treatment until the first documentation of PD or death due to any cause, whichever occurred first (approximately 46.2 months of treatment exposure)
Duration of Response (DOR) Per RECIST v1.1 According to INV	DOR was defined as the time from the date of first documented objective response (CR or PR that was subsequently confirmed) to the date of first documented PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: a >= 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Kaplan-Meier methods was used for analysis.	From the first documented objective response until the first documentation of PD or death, whichever occurred first (approximately 46.2 months)
Disease Control Rate (DCR) Per RECIST v1.1	DCR was defined as percentage of participants with confirmed CR, PR or stable disease ([SD] or non-CR/non-PD) per RECIST v1.1. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: a >= 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20 % increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. 95% CI was computed using Clopper-Pearson method.	From first dose of study treatment until PD or death, whichever occurred first (approximately 46.2 months)
Overall Survival (OS)	OS was defined as the time from the start of study treatment to the date of death due to any cause. Participants who were not known to have died at the end of study follow-up, observation of OS was censored on the date the participant was last known to be alive (i.e., the date of last contact). For participants without data beyond the day of treatment initiation, OS was censored on the date of treatment initiation. Kaplan-Meier methods was used for analysis.	From date of start of study treatment until date of death or censoring date (approximately 46.2 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product which did not necessarily have a causal relationship with this treatment. AEs included all non-serious adverse events (non-SAEs) and SAEs. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib or trastuzumab deruxtecan) and up through 30 days after the last dose of study treatment.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
Number of Participants With Serious Adverse Events (SAEs)	An SAE was an AE that at any dose, met any of the following criteria: resulted in death, was life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or disability (substantial disruption of the participant's ability to conduct normal life functions), congenital anomaly/birth defect or considered medically significant.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
Number of Participants With Treatment Emergent Adverse Events Based on Severity	An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib or trastuzumab deruxtecan) and up through 30 days after the last dose of study treatment. AEs were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 where, grade 1= mild; grade 2= moderate; grade 3= severe; grade 4= life-threatening; grade 5= death.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
Number of Participants With Treatment Related TEAEs	An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib or trastuzumab deruxtecan) and up through 30 days after the last dose of study treatment. Relatedness of AEs to study treatment was determined by the investigator.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
Number of Participants With Treatment Emergent Clinical Laboratory Abnormalities	Laboratory abnormalities included: hematology; hemoglobin increased and decreased, leukocytes decreased, lymphocytes increased and decreased, neutrophils decreased and platelets decreased. Chemistry: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine, magnesium, potassium, sodium and total bilirubin increased and glucose, magnesium, potassium and sodium decreased. Treatment-emergent laboratory abnormalities were defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. Laboratory test results were graded according to NCI CTCAE version 4.03, where Grade 0: no AE, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Number of participants with any grade are reported in this outcome measure.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
Number of Participants With TEAEs Leading to Dose Modification	An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib or trastuzumab deruxtecan) and up through 30 days after the last dose of study treatment. Dose modification included dose reduction, dose delay, dose hold and dose interruption. Number of participants with TEAEs leading to any type of dose modification for tucatinib and T-DXd are reported in this outcome measure.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
Number of Participants With TEAEs Leading to Treatment Discontinuation	An AE was defined was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib or trastuzumab deruxtecan) and up through 30 days after the last dose of study treatment. In this outcome measure, participants with TEAEs leading to discontinuation of tucatinib and T-DXd treatment is reported.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
Number of Participants According to Change From Baseline Categories in Ejection Fraction	Cardiac ejection fraction was assessed using multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO). Baseline was defined as most recent non-missing assessment on or before first dose date. Number of participants according to change from baseline in ejection fraction categories (i.e., no decrease, decrease <10%, decrease 10-<20% and decrease >=20%) is reported in this outcome measure.	Baseline up to 30 days after last dose of study treatment (approximately 47.2 months)
Number of Participants With Clinically Significant Vital Signs	Vital signs included body temperature, respiratory rate, heart rate, oxygen saturation, and systolic blood pressure (SBP) and diastolic blood pressure (DBP). The clinically significant vital signs were defined as: heart rate > 100 beats per minute (bpm), temperature >=38.0 degrees Celsius (C), respiratory rate > 20 breaths per minute and oxygen saturation < 88%; SBP >=120 millimeters of mercury (mmHg) or DBP >=80 mmHg; SBP >=140 mmHg or DBP >=90 mmHg and SBP >=160 mmHg or DBP>=100 mmHg.	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)

Collaborators and Investigators

• Sponsor: Seagen, a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): July 15, 2024
• Study Completion (Actual): March 7, 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 (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic breast cancer; Seattle Genetics; HER2+ breast cancer; Stage IV breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Immunoconjugates; trastuzumab deruxtecan; tucatinib
• Other Study ID Numbers: SGNTUC-025; C4251006 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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