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

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04539938

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HER2 Positive Breast Cancer	Drug: tucatinib Drug: trastuzumab deruxtecan	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Oct 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Duration of response (DOR) per RECIST v1.1 according to investigator assessment [From start of treatment up to approximately 3 years]
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
Progression-free survival (PFS) per RECIST v1.1 according to investigator assessment [From start of treatment up to approximately 3 years]
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
Disease control rate (DCR) per RECIST v1.1 according to investigator assessment [From start of treatment up to approximately 3 years]
DCR is defined as the proportion of subjects with confirmed CR, PR or stable disease according to RECIST v1.1
Overall survival (OS) [From start of treatment up to approximately 5 years]
OS is defined as the time from treatment initiation to death due to any cause
Incidence of adverse events (AEs) [From start of treatment up to approximately 3 years]
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.
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona	United States	85704
3	City of Hope National Medical Center	Duarte	California	United States	91010-3000
4	UCLA Department of Medicine - Hematology & Oncology	Los Angeles	California	United States	90095
5	University of California at San Francisco	San Francisco	California	United States	94134
6	University of Colorado Hospital / University of Colorado	Aurora	Colorado	United States	80045-0510
7	Lombardi Cancer Center / Georgetown University Medical Center	Washington	District of Columbia	United States	20007
8	Florida Cancer Specialists - North Region	Saint Petersburg	Florida	United States	33705
9	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia	United States	30322
10	Georgia Cancer Specialists / Northside Hospital Cancer Institute	Sandy Springs	Georgia	United States	30341
11	James Graham Brown Cancer Center / University of Louisville	Louisville	Kentucky	United States	40202
12	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
13	Allina Health Cancer Institute	Minneapolis	Minnesota	United States	55407
14	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
15	Saint Luke's Cancer Institute LLC	Kansas City	Missouri	United States	64113
16	HCA Midwest Health Kansas City	Kansas City	Missouri	United States	64132
17	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
18	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
19	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
20	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina	United States	27599
21	Wake Forest Baptist Medical Center / Wake Forest University	Winston-Salem	North Carolina	United States	27157
22	Providence Portland Medical Center	Portland	Oregon	United States	97213
23	Northwest Cancer Specialists, P.C.	Tigard	Oregon	United States	97223
24	Magee Womens Hospital of UPMC	Pittsburgh	Pennsylvania	United States	15213
25	Chattanooga Oncology and Hematology Associates/Tennessee Oncology-Memorial Plaza	Chattanooga	Tennessee	United States	37404
26	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
27	Texas Oncology - Presbyterian Cancer Center Dallas	Dallas	Texas	United States	75231
28	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
29	MD Anderson Cancer Center / University of Texas	Houston	Texas	United States	77030-4095
30	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
31	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Salem	Virginia	United States	24153
32	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington	United States	98109-1023
33	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin	United States	53792