HER2 Positive Breast Cancer
Conditions
Keywords
HER2+ breast cancer, Metastatic breast cancer, Stage IV breast cancer, Seattle Genetics
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.
Interventions
DRUGtucatinib
300 mg orally twice daily
DRUGtrastuzumab deruxtecan
5.4 mg/kg via intravenous (into the vein; IV) infusion on Day 1 of each of 21-day cycle
Sponsors
Seagen, a wholly owned subsidiary of Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| Overall Survival (OS) | From date of start of study treatment until date of death or censoring date (approximately 46.2 months) | 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. |
| 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) | 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. |
| 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 (approximately 47.2 months) | 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 Treatment Emergent 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 (approximately 47.2 months) | 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. AEs were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 where, grade 1= mild; grade 2= moderate; grade 3= severe; grade 4= life-threatening; grade 5= death. |
| Number of Participants With Treatment Related 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) | 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. Relatedness of AEs to study treatment was determined by the investigator. |
| Number of Participants With Treatment Emergent Clinical Laboratory Abnormalities | From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months) | Laboratory abnormalities included: hematology; hemoglobin increased and decreased, leukocytes decreased, lymphocytes increased and decreased, neutrophils decreased and platelets decreased. Chemistry: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine, magnesium, potassium, sodium and total bilirubin increased and glucose, magnesium, potassium and sodium decreased. Treatment-emergent laboratory abnormalities were defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. Laboratory test results were graded according to NCI CTCAE version 4.03, where Grade 0: no AE, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Number of participants with any grade are reported in this outcome measure. |
| 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 (approximately 47.2 months) | 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. Dose modification included dose reduction, dose delay, dose hold and dose interruption. Number of participants with TEAEs leading to any type of dose modification for tucatinib and T-DXd are reported in this outcome measure. |
| 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 (approximately 47.2 months) | 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. In this outcome measure, participants with TEAEs leading to discontinuation of tucatinib and T-DXd treatment is reported. |
| Number of Participants According to Change From Baseline Categories in Ejection Fraction | Baseline up to 30 days after last dose of study treatment (approximately 47.2 months) | Cardiac ejection fraction was assessed using multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO). Baseline was defined as most recent non-missing assessment on or before first dose date. Number of participants according to change from baseline in ejection fraction categories (i.e., no decrease, decrease \<10%, decrease 10-\<20% and decrease \>=20%) is reported in this outcome measure. |
| 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 (approximately 47.2 months) | Vital signs included body temperature, respiratory rate, heart rate, oxygen saturation, and systolic blood pressure (SBP) and diastolic blood pressure (DBP). The clinically significant vital signs were defined as: heart rate \> 100 beats per minute (bpm), temperature \>=38.0 degrees Celsius (C), respiratory rate \> 20 breaths per minute and oxygen saturation \< 88%; SBP \>=120 millimeters of mercury (mmHg) or DBP \>=80 mmHg; SBP \>=140 mmHg or DBP \>=90 mmHg and SBP \>=160 mmHg or DBP\>=100 mmHg. |
Countries
United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
Participants diagnosed with unresectable locally advanced or metastatic (LA/M) human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC) with or without brain metastases, who received prior treatment with a taxane and trastuzumab or progressed within 6 months after neoadjuvant or adjuvant treatment involving a regimen including a taxane and trastuzumab (with or without pertuzumab) were enrolled at 24 sites in the United States.
Pre-assignment details
A total of 94 participants were screened of which 24 failed screening, and 70 participants were enrolled in the study. Participants who continued to receive clinical benefit after end of study could continue to receive study treatment during the long-term extension phase (LTEP).
Participants by arm
| Arm | Count |
|---|---|
| Total Participants Participants with HER2+ LA/mBC with or without history of brain metastases received tucatinib 300mg PO BID on Days 1 to 21 and Trastuzumab Deruxtecan (T-DXd) 5.4 mg/kg IV on Day 1 of each 21-day cycle. Participants received treatment until unacceptable toxicity, PD, investigator or participants decision to discontinue, or study closure. | 70 |
| Total | 70 |
Baseline characteristics
| Characteristic | Total Participants |
|---|---|
| Age, Continuous | 55.5 Years STANDARD_DEVIATION 13.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| HER2 testing results IHC 2+ and/or Fluorescence in situ hybridization + | 28 Participants |
| HER2 testing results Immunohistochemistry (IHC) 3 plus (+) | 41 Participants |
| HER2 testing results Other | 1 Participants |
| Presence or history of treated or untreated brain metastases No | 43 Participants |
| Presence or history of treated or untreated brain metastases Yes | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 56 Participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 39 / 70 |
| other Total, other adverse events | 70 / 70 |
| serious Total, serious adverse events | 25 / 70 |
Outcome results
Primary
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)
Population: Response-evaluable analysis set included all participants with measurable disease who (1) had a baseline disease assessment, (2) received at least one dose of study drug (tucatinib and/or trastuzumab deruxtecan), and (3) had at least 1 post-baseline assessment or discontinued treatment due to PD, clinical progression, toxicity, or death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Participants | Confirmed Objective Response Rate (cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 According to Investigator (INV) Assessment | 51.4 Percentage of participants |
Secondary
Change From Baseline in Ejection Fraction
Cardiac ejection fraction will be assessed using multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
Time frame: Baseline and end of treatment
Population: The all-treated participants included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Secondary
Disease Control Rate (DCR) Per RECIST v1.1
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.
Time frame: From the first dose study treatment until PD or death, whichever occurred first
Population: The response-evaluable analysis set included all participants with measurable disease who (1) had a baseline disease assessment, (2) received at least one dose of study drug (tucatinib and/or trastuzumab deruxtecan), and (3) had at least 1 post-baseline assessment or discontinued treatment due to PD, clinical progression, toxicity, or death.
Secondary
Duration of Response (DOR) Per RECIST v1.1 According to INV
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.
Time frame: From the first documented objective response until the first documentation of PD or death, whichever occurred first
Population: The response-evaluable analysis set included all participants with measurable disease who (1) had a baseline disease assessment, (2) received at least one dose of study drug (tucatinib and/or trastuzumab deruxtecan), and (3) had at least 1 post-baseline assessment or discontinued treatment due to PD, clinical progression, toxicity, or death.
Secondary
Number of Participants With Adverse Events Based on Severity
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.
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Secondary
Number of Participants With Clinical Laboratory Abnormalities
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.
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Population: The all-treated participants included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Secondary
Number of Participants With Clinically Significant Vital Signs
Vital signs will include body temperature, respiratory rate, heart rate, and systolic and diastolic blood pressure.
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Population: The all-treated participants included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Secondary
Number of Participants With Serious Adverse Events (SAEs)
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.
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Secondary
Number of Participants With TEAEs Leading to Dose Modification
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.
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Population: The all-treated participants included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Secondary
Number of Participants With TEAEs Leading to Treatment Discontinuation
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Population: The all-treated participants included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs)
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.
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Population: The all-treated participants included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Secondary
Number of Participants With Treatment Related Adverse Events
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.
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment
Secondary
Overall Survival (OS)
OS was defined as the time from the start of study treatment to the date of death due to any cause.
Time frame: From date of start of study treatment until date of death or censoring date
Population: The all-treated participants included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Secondary
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 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.
Time frame: From the start of study treatment until the first documentation of PD or death, whichever occurred first
Population: The all treated participants includes all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).