A Study of Tucatinib Plus Trastuzumab Deruxtecan in HER2+ Breast Cancer

HER2 Positive Breast Cancer Clinical Trial

— HER2CLIMB-04  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04539938
• Other study ID #: SGNTUC-025
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 1, 2020
• Est. completion date: October 31, 2025

Study information

• Verified date: March 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: October 31, 2025
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2 Positive Breast Cancer

Intervention

Drug:
• tucatinib
300 mg orally twice daily
• trastuzumab deruxtecan
5.4 mg/kg via intravenous (into the vein; IV) infusion on Day 1 of each of 21-day cycle

Locations

Country	Name	City	State
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	University of Colorado Hospital / University of Colorado	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina
United States	Chattanooga Oncology and Hematology Associates/Tennessee Oncology-Memorial Plaza	Chattanooga	Tennessee
United States	Texas Oncology - DFW	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	HCA Midwest Health Kansas City	Kansas City	Missouri
United States	Saint Luke's Cancer Institute LLC	Kansas City	Missouri
United States	UCLA Department of Medicine - Hematology & Oncology	Los Angeles	California
United States	James Graham Brown Cancer Center / University of Louisville	Louisville	Kentucky
United States	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin
United States	Allina Health Cancer Institute	Minneapolis	Minnesota
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Magee Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Florida Cancer Specialists - North Region	Saint Petersburg	Florida
United States	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Salem	Virginia
United States	University of California at San Francisco	San Francisco	California
United States	Georgia Cancer Specialists / Northside Hospital Cancer Institute	Sandy Springs	Georgia
United States	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	Northwest Cancer Specialists, P.C.	Tigard	Oregon
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Lombardi Cancer Center / Georgetown University Medical Center	Washington	District of Columbia
United States	Wake Forest Baptist Medical Center / Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Incidence of laboratory abnormalities		From start of treatment up to approximately 3 years
Secondary	Incidence of dose modifications		From start of treatment up to approximately 3 years
Secondary	Incidence of treatment discontinuations		From start of treatment up to approximately 3 years