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

Seagen, a wholly owned subsidiary of Pfizer70 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HER2 Positive Breast Cancer

Interventions

tucatinibDRUG

300 mg orally twice daily

trastuzumab deruxtecanDRUG

5.4 mg/kg via intravenous (into the vein; IV) infusion on Day 1 of each of 21-day cycle

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (140)

Outcomes

Primary Outcomes

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.

Time frame: 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

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.

Time frame: 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.

Data from ClinicalTrials.gov

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University Of Alabama at Birmingham

Birmingham, Alabama, United States

University of Alabama at Birmingham, IDS Pharmacy

Birmingham, Alabama, United States

University Of Alabama at Birmingham

Birmingham, Alabama, United States

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

UCLA Hematology/Oncology - Alhambra

Alhambra, California, United States

UCLA Hematology/Oncology - Burbank

Burbank, California, United States

City of Hope (City of Hope National Medical Center, City of Hope Medical center)

Duarte, California, United States

City of Hope Investigational Drug Services (IDS)

Duarte, California, United States

UCLA Hematology/Oncology - Laguna Hills

Laguna Hills, California, United States

...and 130 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.