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

Phase 2

Active, not recruiting

Conditions: HER2 Positive Breast Cancer

Interventions: Drug: tucatinib
Drug: trastuzumab deruxtecan

Registration Number: NCT04539938

Lead Sponsor: Seagen, a wholly owned subsidiary of Pfizer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	tucatinib	Tucatinib + trastuzumab deruxtecan
Single Arm	trastuzumab deruxtecan	Tucatinib + trastuzumab deruxtecan

Primary Outcome Measures

Name	Time	Method
Confirmed Objective Response Rate (cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 According to Investigator (INV) Assessment	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)	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.

Secondary Outcome Measures

Name	Time	Method
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, whichever occurred first	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 includes the baseline sum if that is 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 is also considered progression.
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	DOR was defined the time from the date of the first documented objective response (CR or PR that is subsequently confirmed) to the date of the 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 includes the baseline sum if that is 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 is 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.
Disease Control Rate (DCR) Per RECIST v1.1	From the first dose study treatment until PD or death, whichever occurred first	DCR was defined as the 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.
Overall Survival (OS)	From date of start of study treatment until date of death or censoring date	OS was defined as the time from the start of study treatment to the date of death due to any cause.
Number of Participants With Treatment Emergent Adverse Events (AEs)	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment	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 treatment-emergent adverse event (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.
Number of Participants With Serious Adverse Events (SAEs)	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment	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.
Number of Participants With Adverse Events Based on Severity	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment	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 treatment-emergent adverse event (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 criteria where, grade 1= mild; grade 2= moderate; grade 3= severe; grade 4= life-threatening; grade 5= death.
Number of Participants With Treatment Related Adverse Events	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment	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. Relatedness of AEs to study treatment was determined by the investigator.
Number of Participants With Clinical Laboratory Abnormalities	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment	Following laboratory parameters will be assessed: Serum chemistry included: bicarbonate, blood urea nitrogen, calcium, creatinine, chloride, glucose, magnesium, phosphorus, potassium, and sodium. liver function tests (LFTs) include albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (and both direct and indirect bilirubin when total bilirubin is \> upper limit of normal (ULN), and total protein. white blood cell counts with 5-part differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), platelet count, hemoglobin, and hematocrit. Coagulation: international normalized ratio (INR), prothrombin time (PT), and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT), A serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test.
Number of Participants With TEAEs Leading to Dose Modification	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment	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. Participants experienced tucatinib dose modification due to TEAEs. Dose modification included dose reduction, dose delay, dose hold, drug interruption.
Number of Participants With TEAEs Leading to Treatment Discontinuation	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Change From Baseline in Ejection Fraction	Baseline and end of treatment	Cardiac ejection fraction will be assessed using multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
Number of Participants With Clinically Significant Vital Signs	From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment	Vital signs will include body temperature, respiratory rate, heart rate, and systolic and diastolic blood pressure.

Trial Locations

Locations (33): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Arizona Oncology Associates, PC - HOPE
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Tucson, Arizona, United States
City of Hope
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Duarte, California, United States
UCLA Department of Medicine - Hematology & Oncology
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Los Angeles, California, United States
University of California at San Francisco
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San Francisco, California, United States
University of Colorado Hospital / University of Colorado
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Aurora, Colorado, United States
Lombardi Cancer Center / Georgetown University Medical Center
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Washington, District of Columbia, United States
Florida Cancer Specialists - North Region
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Saint Petersburg, Florida, United States
Winship Cancer Institute / Emory University School of Medicine
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Atlanta, Georgia, United States
Georgia Cancer Specialists / Northside Hospital Cancer Institute
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Sandy Springs, Georgia, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States