Trial Outcomes & Findings for A Study of Tucatinib Plus Trastuzumab Deruxtecan in HER2+ Breast Cancer (NCT NCT04539938)

Last Updated: 2025-09-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

70 participants

Primary outcome timeframe

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)

Results posted on

2025-09-30

Participant Flow

Participants diagnosed with unresectable locally advanced or metastatic (LA/M) human epidermal growth factor receptor 2 positive (HER2+) breast cancer 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.

A total of 94 participants were screened of which 24 failed screening and 70 participants were enrolled in the study. Results are presented for primary outcome measures at data cutoff 15 July 2024 (primary completion date \[PCD\]). Remaining outcome measures would be reported upon completion of their analyses at study completion date.

Participant milestones

Participant milestones
Measure	Total Participants Participants with HER2+ LA/mBC with or without history of brain metastases received tucatinib 300 milligram (mg) orally (PO) twice daily (BID) on Days 1 to 21 and Trastuzumab Deruxtecan (T-DXd) 5.4 milligram per kilogram (mg/kg) intravenous (IV) on Day 1 of each 21-day cycle. Participants received treatment until unacceptable toxicity, progressive disease (PD), investigator or participants decision to discontinue, or study closure.
Overall Study STARTED	70
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Total Participants Participants with HER2+ LA/mBC with or without history of brain metastases received tucatinib 300 milligram (mg) orally (PO) twice daily (BID) on Days 1 to 21 and Trastuzumab Deruxtecan (T-DXd) 5.4 milligram per kilogram (mg/kg) intravenous (IV) on Day 1 of each 21-day cycle. Participants received treatment until unacceptable toxicity, progressive disease (PD), investigator or participants decision to discontinue, or study closure.
Overall Study Death	30
Overall Study Withdrawal by Subject	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total Participants n=70 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.
Age, Continuous	55.5 Years STANDARD_DEVIATION 13.2 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	56 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Presence or history of treated or untreated brain metastases Yes	27 Participants n=5 Participants
Presence or history of treated or untreated brain metastases No	43 Participants n=5 Participants
HER2 testing results Immunohistochemistry (IHC) 3 plus (+)	41 Participants n=5 Participants
HER2 testing results IHC 2+ and/or Fluorescence in situ hybridization +	28 Participants n=5 Participants
HER2 testing results Other	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Total Participants n=70 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.
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 Interval 39.2 to 63.6

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

OS was defined as the time from the start of study treatment to the date of death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Cardiac ejection fraction will be assessed using multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Vital signs will include body temperature, respiratory rate, heart rate, and systolic and diastolic blood pressure.

Outcome measures

Outcome data not reported

Adverse Events

Total Participants

Serious events: 25 serious events

Other events: 70 other events

Deaths: 33 deaths

Serious adverse events

Serious adverse events
Measure	Total Participants n=70 participants at risk 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.
Blood and lymphatic system disorders Febrile neutropenia	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Cardiac disorders Ventricular fibrillation	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Abdominal distension	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Abdominal pain	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Diarrhoea	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Enterocolitis	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Nausea	2.9% 2/70 • Number of events 2 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Obstructive pancreatitis	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Vomiting	2.9% 2/70 • Number of events 2 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
General disorders Fatigue	2.9% 2/70 • Number of events 2 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Bacteraemia	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Pneumonia	4.3% 3/70 • Number of events 3 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Tooth infection	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Urinary tract infection	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Injury, poisoning and procedural complications Fall	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Injury, poisoning and procedural complications Overdose	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Injury, poisoning and procedural complications Subdural haematoma	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Metabolism and nutrition disorders Dehydration	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Metabolism and nutrition disorders Hypokalaemia	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Metabolism and nutrition disorders Hyponatraemia	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Musculoskeletal and connective tissue disorders Arthralgia	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Nervous system disorders Brain oedema	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Nervous system disorders Trigeminal neuralgia	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Psychiatric disorders Confusional state	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Renal and urinary disorders Acute kidney injury	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	4.3% 3/70 • Number of events 3 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Vascular disorders Haematoma	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Vascular disorders Hypertension	1.4% 1/70 • Number of events 1 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).

Other adverse events

Other adverse events
Measure	Total Participants n=70 participants at risk 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.
Blood and lymphatic system disorders Anaemia	10.0% 7/70 • Number of events 8 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Blood and lymphatic system disorders Neutropenia	7.1% 5/70 • Number of events 14 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Eye disorders Dry eye	7.1% 5/70 • Number of events 6 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Eye disorders Vision blurred	15.7% 11/70 • Number of events 12 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Abdominal pain	12.9% 9/70 • Number of events 16 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Constipation	52.9% 37/70 • Number of events 59 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Diarrhoea	78.6% 55/70 • Number of events 103 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Dry mouth	8.6% 6/70 • Number of events 6 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Gastrooesophageal reflux disease	10.0% 7/70 • Number of events 8 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Haemorrhoids	7.1% 5/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Nausea	77.1% 54/70 • Number of events 90 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Stomatitis	14.3% 10/70 • Number of events 12 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Gastrointestinal disorders Vomiting	60.0% 42/70 • Number of events 68 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
General disorders Chills	10.0% 7/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
General disorders Fatigue	71.4% 50/70 • Number of events 64 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
General disorders Influenza like illness	7.1% 5/70 • Number of events 6 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
General disorders Malaise	5.7% 4/70 • Number of events 5 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
General disorders Oedema peripheral	11.4% 8/70 • Number of events 10 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
General disorders Pyrexia	10.0% 7/70 • Number of events 9 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations COVID-19	15.7% 11/70 • Number of events 11 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Conjunctivitis	5.7% 4/70 • Number of events 4 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Sinusitis	5.7% 4/70 • Number of events 5 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Upper respiratory tract infection	15.7% 11/70 • Number of events 14 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Infections and infestations Urinary tract infection	24.3% 17/70 • Number of events 34 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Injury, poisoning and procedural complications Fall	10.0% 7/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Investigations Alanine aminotransferase increased	10.0% 7/70 • Number of events 10 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Investigations Aspartate aminotransferase increased	8.6% 6/70 • Number of events 8 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Investigations Blood bilirubin increased	5.7% 4/70 • Number of events 11 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Investigations Blood creatinine increased	7.1% 5/70 • Number of events 8 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Investigations Neutrophil count decreased	11.4% 8/70 • Number of events 11 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Investigations Weight decreased	21.4% 15/70 • Number of events 16 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Investigations Weight increased	5.7% 4/70 • Number of events 4 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Metabolism and nutrition disorders Decreased appetite	35.7% 25/70 • Number of events 32 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Metabolism and nutrition disorders Dehydration	11.4% 8/70 • Number of events 18 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Metabolism and nutrition disorders Hypokalaemia	28.6% 20/70 • Number of events 29 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Metabolism and nutrition disorders Hypomagnesaemia	15.7% 11/70 • Number of events 19 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Musculoskeletal and connective tissue disorders Arthralgia	12.9% 9/70 • Number of events 12 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Musculoskeletal and connective tissue disorders Back pain	11.4% 8/70 • Number of events 9 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Musculoskeletal and connective tissue disorders Bone pain	11.4% 8/70 • Number of events 9 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 7/70 • Number of events 12 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Musculoskeletal and connective tissue disorders Muscular weakness	5.7% 4/70 • Number of events 5 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Musculoskeletal and connective tissue disorders Myalgia	7.1% 5/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Nervous system disorders Dizziness	14.3% 10/70 • Number of events 14 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Nervous system disorders Dysgeusia	10.0% 7/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Nervous system disorders Headache	30.0% 21/70 • Number of events 32 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Nervous system disorders Peripheral sensory neuropathy	15.7% 11/70 • Number of events 11 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Psychiatric disorders Insomnia	11.4% 8/70 • Number of events 8 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Renal and urinary disorders Dysuria	5.7% 4/70 • Number of events 4 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Renal and urinary disorders Pollakiuria	7.1% 5/70 • Number of events 5 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Cough	20.0% 14/70 • Number of events 15 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.9% 9/70 • Number of events 10 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Epistaxis	10.0% 7/70 • Number of events 10 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.0% 7/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.6% 6/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.7% 4/70 • Number of events 4 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Skin and subcutaneous tissue disorders Alopecia	24.3% 17/70 • Number of events 17 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Skin and subcutaneous tissue disorders Rash	7.1% 5/70 • Number of events 16 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Skin and subcutaneous tissue disorders Rash maculo-papular	5.7% 4/70 • Number of events 5 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Vascular disorders Hot flush	11.4% 8/70 • Number of events 9 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).
Vascular disorders Hypotension	5.7% 4/70 • Number of events 7 • From start of study treatment (Day 1) up to 30 days after last dose of study treatment (approximately up to 43.5 months) Same event may appear as both non-serious adverse event and serious adverse event (SAE); however, are presented as distinct events. Event may be categorized as serious in 1 participant and non-serious in another or may have experienced both SAE and non-SAE. The all-treated participants analysis set included all participants who received any amount of study drug (tucatinib and/or trastuzumab deruxtecan).

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 8007181021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publication until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER