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
2 other identifiers
interventional
70
1 country
140
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Dec 2020
Typical duration for phase_2
140 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 31, 2020
CompletedFirst Posted
Study publicly available on registry
September 7, 2020
CompletedStudy Start
First participant enrolled
December 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 15, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
March 7, 2025
CompletedResults Posted
Study results publicly available
July 31, 2025
CompletedMarch 23, 2026
March 1, 2026
3.6 years
August 31, 2020
July 14, 2025
March 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (13)
Progression-Free Survival (PFS) Per RECIST v1.1 According to INV
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
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
From first dose of study treatment until PD or death, whichever occurred first (approximately 46.2 months)
Overall Survival (OS)
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)
From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months)
- +8 more secondary outcomes
Study Arms (1)
Single Arm
EXPERIMENTALTucatinib + trastuzumab deruxtecan
Interventions
300 mg orally twice daily
5.4 mg/kg via intravenous (into the vein; IV) infusion on Day 1 of each of 21-day cycle
Eligibility Criteria
You may qualify if:
- 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
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (140)
University Of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
University of Alabama at Birmingham, IDS Pharmacy
Birmingham, Alabama, 35249, United States
University Of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, 85704, United States
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, 85711, United States
UCLA Hematology/Oncology - Alhambra
Alhambra, California, 91801, United States
UCLA Hematology/Oncology - Burbank
Burbank, California, 91505, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical center)
Duarte, California, 91010, United States
City of Hope Investigational Drug Services (IDS)
Duarte, California, 91010, United States
UCLA Hematology/Oncology - Laguna Hills
Laguna Hills, California, 92653, United States
(IRB# 20-001502) Ronald Reagan UCLA Medical Center, Drug Information Center
Los Angeles, California, 90095, United States
UCLA Hematology/Oncology
Los Angeles, California, 90095, United States
UCLA Hematology/Oncology - Pasadena
Pasadena, California, 91105, United States
Zuckerberg San Francisco General Hospital- Breast Clinic
San Francisco, California, 94110, United States
Zuckerberg San Francisco General Hospital- Oncology Clinic
San Francisco, California, 94110, United States
University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158, United States
UCLA Hematology/Oncology - San Luis Obispo
San Luis Obispo, California, 93401, United States
UCLA Hematology/Oncology - Santa Barbara
Santa Barbara, California, 93105, United States
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, 90404, United States
UCLA Hematology/Oncology Parkside
Santa Monica, California, 90404, United States
UCLA Hematology/Oncology - Ventura
Ventura, California, 93003, United States
UCLA Hematology/Oncology - Westlake
Westlake Village, California, 91361, United States
University of Colorado Denver CTO/CTRC - Outpatient.
Aurora, Colorado, 80045, United States
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
Aurora, Colorado, 80045, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
Aurora, Colorado, 80045, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
Aurora, Colorado, 80045, United States
UC Health Lone Tree Medical Center
Lone Tree, Colorado, 80124, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
Washington Cancer Institute at MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Florida Cancer Specialists
Altamonte Springs, Florida, 32701, United States
Florida Cancer Specialists
Brandon, Florida, 33511, United States
Florida Cancer Specialists
Clearwater, Florida, 33761, United States
Florida Cancer Specialists
Gainesville, Florida, 32605, United States
Florida Cancer Specialists
Largo, Florida, 33770, United States
Florida Cancer Specialists
Lecanto, Florida, 34461, United States
Florida Cancer Specialists
Ocala, Florida, 34474, United States
Florida Cancer Specialists
Orange City, Florida, 32763, United States
Florida Cancer Specialists
Orlando, Florida, 32806, United States
Florida Cancer Specialists
St. Petersburg, Florida, 33705, United States
Florida Cancer Specialists
Tampa, Florida, 33607, United States
Florida Cancer Specialists
Tavares, Florida, 32778, United States
Florida Cancer Specialists
The Villages, Florida, 32159, United States
Florida Cancer Specialists
Trinity, Florida, 34655, United States
Florida Cancer Specialists
Winter Park, Florida, 32789, United States
Northside Hospital, Inc - GCS/Athens
Athens, Georgia, 30606, United States
Winship Cancer Institute @ Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
The Emory Clinic
Atlanta, Georgia, 30322, United States
Winship Cancer Institute / Emory University School of Medicine
Atlanta, Georgia, 30322, United States
Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Atlanta Cancer Care - Atlanta
Atlanta, Georgia, 30342, United States
Northside Hospital, Inc. - Central Research Department
Atlanta, Georgia, 30342, United States
Northside Hospital, Inc. - GCS/Center Pointe
Atlanta, Georgia, 30342, United States
Northside Hospital, Inc - GCS/Blairsville
Blairsville, Georgia, 30512, United States
Northside Hospital, Inc - GCS/Canton
Canton, Georgia, 30114, United States
Atlanta Cancer Care - Cumming
Cumming, Georgia, 30041, United States
Northside Hospital, Inc. - GCS/Decatur
Decatur, Georgia, 30033, United States
NHCI Suburban Hematology-oncology Associates - Duluth
Duluth, Georgia, 30096, United States
NHCI Suburban Hematology-oncology Associates - lawrenceville
Lawrenceville, Georgia, 30046, United States
Northside Hospital, Inc - GCS/Macon
Macon, Georgia, 31217, United States
Northside Hospital, Inc. - GCS/Marietta
Marietta, Georgia, 30060, United States
Atlanta Cancer Care - Stockbridge
Stockbridge, Georgia, 30281, United States
Harry and Jeanette Weinberg Cancer Institute at Franklin Square
Baltimore, Maryland, 21237, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Dana Farber Cancer Institute- Chestnut Hill
Newton, Massachusetts, 02459, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Minnesota Oncology Hematology, PA
Coon Rapids, Minnesota, 55433, United States
Mercy Hospital - Unity Campus
Fridley, Minnesota, 55432, United States
Minnesota Oncology Hematology, PA
Fridley, Minnesota, 55433, United States
Minnesota Oncology Hematology, PA
Minneapolis, Minnesota, 55404, United States
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Allina Health Cancer institute
Minneapolis, Minnesota, 55407, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Allina Health Cancer Institute
Saint Paul, Minnesota, 55102, United States
Minnesota Oncology Hematology PA
Saint Paul, Minnesota, 55102, United States
Minnesota Oncology Hematology, PA
Saint Paul, Minnesota, 55102, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68114, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68124, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Papillion, Nebraska, 68046, United States
MSK Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
MSK Monmouth
Middletown, New Jersey, 07748, United States
MSK Bergen
Montvale, New Jersey, 07645, United States
MSK Commack
Commack, New York, 11725, United States
MSK Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy
Long Island City, New York, 11101, United States
Evelyn H. Lauder Breast and Imaging Center (BAIC).
New York, New York, 10065, United States
MSK Nassau
Uniondale, New York, 11553, United States
Providence Cancer Institute Franz Clinic
Portland, Oregon, 97213, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
UPMC Hillman Cancer Center Passavant North
Cranberry Township, Pennsylvania, 16066, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
UPMC Hillman Cancer Center Mountainview
Greensburg, Pennsylvania, 15601, United States
UPMC Hillman Cancer Center UPMC East
Monroeville, Pennsylvania, 15146, United States
UPMC Hillman Cancer Center Upper Saint Clair
Pittsburgh, Pennsylvania, 15102, United States
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213, United States
University of Pittsburgh Cancer Institute Investigational Drug Service UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
UPMC Cancer Centers William M. Cooper Ambulatory Care Pavilion of the Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
UPMC Hillman Cancer Center UPMC Passavant
Pittsburgh, Pennsylvania, 15237, United States
UPMC Hillman Cancer Center Uniontown
Uniontown, Pennsylvania, 15401, United States
UPMC Hillman Cancer Center Washington
Washington, Pennsylvania, 15301, United States
Tennessee Oncology, PLLC
Chattanooga, Tennessee, 37403, United States
Sarah Cannon Research Institute
Chattanooga, Tennessee, 37404, United States
Tennessee Oncology, PLLC
Chattanooga, Tennessee, 37404, United States
Tennessee Oncology, PLLC
Cleveland, Tennessee, 37311, United States
Tennessee Oncology, PLLC
Dickson, Tennessee, 37055, United States
Tennessee Oncology, PLLC
Franklin, Tennessee, 37067, United States
Tennessee Oncology, PLLC
Gallatin, Tennessee, 37066, United States
Tennessee Oncology, PLLC
Hendersonville, Tennessee, 37075, United States
Tennessee Oncology, PLLC
Hermitage, Tennessee, 37076, United States
Tennessee Oncology, PLLC
Lebanon, Tennessee, 37909, United States
Tennessee Oncology, PLLC
Murfreesboro, Tennessee, 37129, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
The Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37205, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37207, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37211, United States
Tennessee Oncology, PLLC
Shelbyville, Tennessee, 37160, United States
Tennessee Oncology, PLLC
Smyrna, Tennessee, 37167, United States
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
U.T. MD Anderson Cancer Center
Houston, Texas, 77030, United States
US Oncology Investigational Product Center (IPC)
Irving, Texas, 75063, United States
US Oncology Investigational Products Center (IPC)
Irving, Texas, 75063, United States
US Oncology lnvestigational Products Center (IPC)
Irving, Texas, 75063, United States
Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
Blacksburg, Virginia, 24060, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031, United States
Virginia Cancer Specialists, PC
Gainesville, Virginia, 20155, United States
Virginia Cancer Specialists, PC
Leesburg, Virginia, 20176, United States
Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
Low Moor, Virginia, 24457, United States
Virginia Cancer Specialists, PC
Reston, Virginia, 20190, United States
Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
Roanoke, Virginia, 24014, United States
Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
Salem, Virginia, 24153, United States
Oncology & Hematology Associates of Southwest Virginia, Inc. D.B.A Blue Ridge Cancer Care
Wytheville, Virginia, 24382, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
UW Health Oncology - One South Park
Madison, Wisconsin, 53715, United States
University of Wisconsin Clinical Science Center
Madison, Wisconsin, 53792, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 31, 2020
First Posted
September 7, 2020
Study Start
December 1, 2020
Primary Completion
July 15, 2024
Study Completion
March 7, 2025
Last Updated
March 23, 2026
Results First Posted
July 31, 2025
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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.