CClinicalTrials.gg
Sign In
Active, not recruitingNCT05132582HER2CLIMB-05Updated Sep 29, 2026Results posted

A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer

A Phase 3 interventional study of Tucatinib and Trastuzumab in HER2 Positive Breast Cancer, sponsored by Seagen, a wholly owned subsidiary of Pfizer. Active, not recruiting at 307 sites in 23 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Seagen, a wholly owned subsidiary of Pfizer · Phase 3, Interventional, and Treatment

Updated Sep 29, 2026Results postedPrimary outcomes revisedGo to Updates ↓
Phase
Phase 3
Study type
Interventional
Enrollment
654
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.

Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).

In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in.

All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.

Read the detailed description

Control arm: Placebo given orally twice daily plus trastuzumab and pertuzumab every 21 days

Experimental arm: Tucatinib 300 mg given orally twice daily plus trastuzumab and pertuzumab every 21 days

Trastuzumab and pertuzumab will be administered as follows:

  • Trastuzumab will be given intravenously (IV) at a dose of 6 mg/kg or subcutaneously (SC) at a fixed dose of 600 mg, once every 21 days.

AND

  • Pertuzumab will be given IV at 420 mg every 21 days. OR
  • Fixed dose combination of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given SC, once every 21 days, in lieu of trastuzumab and pertuzumab individually.
02

Conditions studied

  • HER2 Positive Breast Cancer

Browse trials for

Keywords

  • HER2+ breast cancer
  • Breast Cancer
  • Metastatic breast cancer
  • Seattle Genetics
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 654 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Seagen, a wholly owned subsidiary of Pfizer is the lead sponsor of 30 studies on the registry; 5 are open to participants now.

Of its 11 completed or terminated interventional studies of FDA-regulated products, 3 (27%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Centrally confirmed HER2+ breast carcinoma according to the 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines prior to randomization (defined as a 3+ score on immunohistochemistry (IHC) and/or 2+ IHC and concurrent positive by ISH).

  • Have unresectable locally advanced or metastatic disease.

    • If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab and pertuzumab received in the early breast cancer setting for advanced HER2+ disease.
  • Have received 4-8 cycles of pre-study induction therapy including only trastuzumab, pertuzumab, and taxane as first-line of therapy for the treatment of advanced breast cancer prior to study enrollment. Participants are eligible provided they are without evidence of disease progression following completion of induction therapy.
  • Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-])
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

  • CNS Inclusion - Based on screening contrast-enhanced brain magnetic resonance imaging (MRI), participants may have any of the following:

    • No evidence of brain metastases
    • Untreated brain metastases which are asymptomatic not needing immediate local treatment and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane

    • Previously treated brain metastases which are asymptomatic

      • Brain metastases previously treated with local therapy must not have progressed since treatment

Exclusion criteria

Exclusion Criteria:

  • Prior treatment with any tyrosine kinase inhibitor targeting HER2 and/or epidermal growth factor receptor (EGFR) including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug)
  • Unable to undergo contrast-enhanced MRI of the brain

  • CNS Exclusion - Based on screening brain MRI and clinical assessment

    • Symptomatic brain metastasis after CNS-directed local therapy
    • Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane
    • Ongoing use of systemic corticosteroids at a total daily dose of >2 mg of dexamethasone (or equivalent)
    • Any untreated brain lesion in an anatomic site which may pose risk to participant
    • Known or suspected leptomeningeal disease (LMD)
    • Poorly controlled (>1/week) seizures, or other persistent neurologic symptoms
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
654 participants (actual)

Study arms

  • Experimental
    Tucatinib + trastuzumab + pertuzumab

    Tucatinib + trastuzumab + pertuzumab

    Drug: Tucatinib · Drug: Trastuzumab · Drug: Pertuzumab · Drug: Combination product: Trastuzumab + Pertuzumab

  • Active comparator
    Placebo + trastuzumab + pertuzumab

    Placebo + trastuzumab + pertuzumab

    Drug: Trastuzumab · Drug: Pertuzumab · Drug: Combination product: Trastuzumab + Pertuzumab · Drug: Placebo

Interventions

  • DrugTucatinib

    300mg given by mouth (orally) twice daily

    Also known as: TUKYSA, ONT-380, ARRY-380

  • DrugTrastuzumab

    6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days

    Also known as: Herceptin, Herceptin Hylecta

  • DrugPertuzumab

    420mg given by IV every 21 days

    Also known as: Perjeta

  • DrugCombination product: Trastuzumab + Pertuzumab

    600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually.

    Also known as: Phesgo

  • DrugPlacebo

    Given orally twice daily

06

What researchers measure

Primary outcomes

  1. Progression-Free Survival (PFS) as Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1

    PFS: time from randomization to the first documented disease progression (PD) (as assessed by investigator per RECIST 1.1) or death from any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum of diameter recorded since the treatment started or the appearance of 1 or more new lesions. Participants without documentation of PD/ death at the time of analysis, were censored at date of last tumor assessment with an overall response of complete response (CR), partial response (PR), stable disease (SD), non-CR/non-PD or no evidence of disease (NED). CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the 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 of diameter since the treatment started. Kaplan-Meier method was used for analysis.

    Time frame: From randomization until the first documentation of PD or death from any cause or censoring date, whichever occurred first (maximum treatment exposure was of 41.3 months)

Secondary outcomes

  1. Overall Survival (OS)

    OS: time from randomization to death due to any cause. For a participant who would not known to have died by the end of study follow-up, observation of OS would be censored on the date the participant was last known to be alive (i.e., the date of last contact).

    Time frame: From the date of randomization until date of death or censoring date (approximately 66.7 months)

  2. PFS as Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.1

    PFS per BICR was defined as the time from the date of randomization to the documented disease progression assessed by BICR according to RECIST v1.1 or death from any cause, whichever occurred first. As per RECIST v1.1, PD: \>=20% increase in sum of diameter of target lesions, taking as reference the smallest sum of diameters recorded since treatment started or appearance of 1 or more new lesions, unequivocal progression of existing non-target lesions. Participants without documentation of PD/ death were censored at date of last tumor assessment with an overall response of CR, PR, SD, non-CR/non-PD or NED. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the 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 of diameter since the treatment started. Kaplan-Meier method was used for analysis.

    Time frame: From randomization until the first documentation of PD or death from any cause or censoring date, whichever occurred first (maximum treatment exposure was of 41.3 months)

  3. Time to Deterioration (TTD) of Health-Related Quality of Life (HRQoL)

    Time to deterioration of HRQoL was defined as time to 10-point decrease in the global health status/QoL scale of the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30). EORTC QLQ-C30 is 30 item questionnaires composed of 5 multi-item functional domains (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, nausea, and vomiting) and 6 single items for symptoms (shortness of breath, loss of appetite, sleep disturbance, constipation, diarrhea and financial impact of the disease), 2 global items (health, overall QoL). Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.

    Time frame: Approximately 66.7 months

  4. Central Nervous System (CNS) PFS as Assessed by Investigator Per RECIST v1.1

    CNS-PFS was defined as the time from randomization to investigator assessed disease progression in brain according to RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, PD: \>= 20% increase in sum of diameter of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started or appearance of 1 or more new lesions, unequivocal progression of existing non-target lesions. Participants without documentation of PD/ death at the time of analysis were censored at date of last tumor assessment with an overall response of CR, PR, SD, non-CR/non-PD or NED. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the 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 of diameter since the treatment started. Kaplan-Meier method was used for analysis.

    Time frame: From randomization until the first documentation of PD or death from any cause or censoring date, whichever occurred first (maximum treatment exposure was of 41.3 months)

  5. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    An adverse event (AE) was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. TEAEs were defined as events that were 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. AEs included both Serious AE (SAEs) and all other AEs. An AE should be classified as a serious SAE if it meets one of the following criteria: fatal, life threatening, requires or prolongs hospitalization, disabling/ incapacitating, congenital anomaly or birth defect, medically significant.

    Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 42.3 months)

  6. Number of Participants With Treatment Emergent Laboratory Abnormalities

    TEAEs were defined as events that were 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. Treatment emergent laboratory abnormalities include: hematology (hemoglobin decreased, hemoglobin increased, leukocytes decreased, neutrophils decreased, platelets decreased); chemistry (alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, creatinine increased, potassium decreased, potassium increased, sodium decreased, sodium increased, total bilirubin increased).

    Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

  7. Number of Participants With TEAEs Leading to Dose Discontinuations

    TEAEs were defined as events that were 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. In this outcome measure, number of participants with TEAEs leading to dose discontinuations with study treatment will be reported.

    Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

  8. Number of Participants With TEAEs Leading to Dose Hold

    TEAEs were defined as events that were 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. In this outcome measure, number of participants with TEAEs leading to dose hold with study treatment will be reported. Dose hold requirements are defined per protocol.

    Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

  9. Number of Participants With TEAEs Leading to Dose Reductions

    TEAEs were defined as events that were 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. In this outcome measure, number of participants with TEAEs leading to dose reductions with tucatinib, trastuzumab and pertuzumab are reported. Dose reduction requirements are defined per protocol.

    Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

  10. Trough Concentration (Ctrough) of Tucatinib

    Concentration at Trough was defined as predose/trough concentration observed directly from data.

    Time frame: Pre-dose on Day 1 of Cycles 2, 3, 4, 5 and 6

Other outcomes

  1. Number of Participants With TEAEs: Through Study Completion

    An AE was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. TEAEs were defined as events that were 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. AEs included both SAEs and all other AEs. An AE should be classified as a serious SAE if it meets one of the following criteria: fatal, life threatening, requires or prolongs hospitalization, disabling/ incapacitating, congenital anomaly or birth defect, medically significant.

    Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

07

Results

Posted Sep 29, 2026

Participant flow

Participant flow — Overall Study
MilestoneTucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + Pertuzumab
Started326328
Intent-to-treat (itt) analysis set326328
Safety analysis set (sas)326324
Completed00
Not completed326328
Withdrew: Death1833
Withdrew: Withdrawal by subject94
Withdrew: Ongoing299291

Outcome measures

PrimaryProgression-Free Survival (PFS) as Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1

PFS: time from randomization to the first documented disease progression (PD) (as assessed by investigator per RECIST 1.1) or death from any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum of diameter recorded since the treatment started or the appearance of 1 or more new lesions. Participants without documentation of PD/ death at the time of analysis, were censored at date of last tumor assessment with an overall response of complete response (CR), partial response (PR), stable disease (SD), non-CR/non-PD or no evidence of disease (NED). CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the 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 of diameter since the treatment started. Kaplan-Meier method was used for analysis.

Time frame:
From randomization until the first documentation of PD or death from any cause or censoring date, whichever occurred first (maximum treatment exposure was of 41.3 months)
Reported as:
Median · Months
Progression-Free Survival (PFS) as Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
MonthsTucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + Pertuzumab
Progression-Free Survival (PFS) as Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.124.9 (21.3 to NA)16.3 (12.6 to 18.7)
Statistical analysis
  • Tucatinib + Trastuzumab + Pertuzumab vs Placebo + Trastuzumab + Pertuzumab · Log Rank · p = <0.0001 · Hazard ratio (hr): 0.641 · 95% CI 0.514 to 0.799Hazard ratio was calculated based on stratified Cox proportional hazards model.
SecondaryOverall Survival (OS)

OS: time from randomization to death due to any cause. For a participant who would not known to have died by the end of study follow-up, observation of OS would be censored on the date the participant was last known to be alive (i.e., the date of last contact).

Time frame:
From the date of randomization until date of death or censoring date (approximately 66.7 months)

Results for this outcome have not been posted.

SecondaryPFS as Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.1

PFS per BICR was defined as the time from the date of randomization to the documented disease progression assessed by BICR according to RECIST v1.1 or death from any cause, whichever occurred first. As per RECIST v1.1, PD: \>=20% increase in sum of diameter of target lesions, taking as reference the smallest sum of diameters recorded since treatment started or appearance of 1 or more new lesions, unequivocal progression of existing non-target lesions. Participants without documentation of PD/ death were censored at date of last tumor assessment with an overall response of CR, PR, SD, non-CR/non-PD or NED. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the 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 of diameter since the treatment started. Kaplan-Meier method was used for analysis.

Time frame:
From randomization until the first documentation of PD or death from any cause or censoring date, whichever occurred first (maximum treatment exposure was of 41.3 months)
Reported as:
Median · Months
PFS as Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.1
MonthsTucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + Pertuzumab
PFS as Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.128.9 (24.3 to NA)16.0 (12.3 to 22.9)
Statistical analysis
  • Tucatinib + Trastuzumab + Pertuzumab vs Placebo + Trastuzumab + Pertuzumab · Log Rank · p = 0.0004 · Hazard ratio (hr): 0.654 · 95% CI 0.517 to 0.828Hazard ratio was calculated based on stratified Cox proportional hazards model.
SecondaryTime to Deterioration (TTD) of Health-Related Quality of Life (HRQoL)

Time to deterioration of HRQoL was defined as time to 10-point decrease in the global health status/QoL scale of the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30). EORTC QLQ-C30 is 30 item questionnaires composed of 5 multi-item functional domains (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, nausea, and vomiting) and 6 single items for symptoms (shortness of breath, loss of appetite, sleep disturbance, constipation, diarrhea and financial impact of the disease), 2 global items (health, overall QoL). Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.

Time frame:
Approximately 66.7 months

Results for this outcome have not been posted.

SecondaryCentral Nervous System (CNS) PFS as Assessed by Investigator Per RECIST v1.1

CNS-PFS was defined as the time from randomization to investigator assessed disease progression in brain according to RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, PD: \>= 20% increase in sum of diameter of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started or appearance of 1 or more new lesions, unequivocal progression of existing non-target lesions. Participants without documentation of PD/ death at the time of analysis were censored at date of last tumor assessment with an overall response of CR, PR, SD, non-CR/non-PD or NED. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the 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 of diameter since the treatment started. Kaplan-Meier method was used for analysis.

Time frame:
From randomization until the first documentation of PD or death from any cause or censoring date, whichever occurred first (maximum treatment exposure was of 41.3 months)
Reported as:
Median · Months
Central Nervous System (CNS) PFS as Assessed by Investigator Per RECIST v1.1
MonthsTucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + Pertuzumab
Central Nervous System (CNS) PFS as Assessed by Investigator Per RECIST v1.1NA (NA to NA)NA (NA to NA)
Statistical analysis
  • Tucatinib + Trastuzumab + Pertuzumab vs Placebo + Trastuzumab + Pertuzumab · Log Rank · p = 0.3041 · Hazard ratio (hr): 0.846 · 95% CI 0.616 to 1.162Hazard ratio was calculated based on stratified Cox proportional hazards model.
SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. TEAEs were defined as events that were 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. AEs included both Serious AE (SAEs) and all other AEs. An AE should be classified as a serious SAE if it meets one of the following criteria: fatal, life threatening, requires or prolongs hospitalization, disabling/ incapacitating, congenital anomaly or birth defect, medically significant.

Time frame:
From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 42.3 months)
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
ParticipantsTucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + Pertuzumab
Number of Participants With Treatment Emergent Adverse Events (TEAEs)323313
SecondaryNumber of Participants With Treatment Emergent Laboratory Abnormalities

TEAEs were defined as events that were 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. Treatment emergent laboratory abnormalities include: hematology (hemoglobin decreased, hemoglobin increased, leukocytes decreased, neutrophils decreased, platelets decreased); chemistry (alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, creatinine increased, potassium decreased, potassium increased, sodium decreased, sodium increased, total bilirubin increased).

Time frame:
From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

Results for this outcome have not been posted.

SecondaryNumber of Participants With TEAEs Leading to Dose Discontinuations

TEAEs were defined as events that were 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. In this outcome measure, number of participants with TEAEs leading to dose discontinuations with study treatment will be reported.

Time frame:
From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

Results for this outcome have not been posted.

SecondaryNumber of Participants With TEAEs Leading to Dose Hold

TEAEs were defined as events that were 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. In this outcome measure, number of participants with TEAEs leading to dose hold with study treatment will be reported. Dose hold requirements are defined per protocol.

Time frame:
From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

Results for this outcome have not been posted.

SecondaryNumber of Participants With TEAEs Leading to Dose Reductions

TEAEs were defined as events that were 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. In this outcome measure, number of participants with TEAEs leading to dose reductions with tucatinib, trastuzumab and pertuzumab are reported. Dose reduction requirements are defined per protocol.

Time frame:
From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

Results for this outcome have not been posted.

SecondaryTrough Concentration (Ctrough) of Tucatinib

Concentration at Trough was defined as predose/trough concentration observed directly from data.

Time frame:
Pre-dose on Day 1 of Cycles 2, 3, 4, 5 and 6
Reported as:
Geometric mean · nanograms per milliliter
Trough Concentration (Ctrough) of Tucatinib
nanograms per milliliterTucatinib + Trastuzumab + Pertuzumab
Cycle 2151.83 ± 180.04
Cycle 3158.63 ± 144.77
Cycle 4137.0 ± 192.19
Cycle 5155.4 ± 180.92
Cycle 6146.03 ± 215.17
Other pre-specifiedNumber of Participants With TEAEs: Through Study Completion

An AE was any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. TEAEs were defined as events that were 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. AEs included both SAEs and all other AEs. An AE should be classified as a serious SAE if it meets one of the following criteria: fatal, life threatening, requires or prolongs hospitalization, disabling/ incapacitating, congenital anomaly or birth defect, medically significant.

Time frame:
From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 66.7 months)

Results for this outcome have not been posted.

Adverse events

Collected over From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum up to 42.3 months). Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tucatinib + Trastuzumab + Pertuzumab18/326 (5.5%)55/326 (16.9%)323/326 (99.1%)
Placebo + Trastuzumab + Pertuzumab33/328 (10.1%)26/324 (8%)313/324 (96.6%)
Most frequent serious events
Showing 10 of 86
Most frequent serious events
EventTucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + Pertuzumab
Alanine aminotransferase increasedInvestigations5/3260/324
Drug-induced liver injuryHepatobiliary disorders4/3260/324
DiarrhoeaGastrointestinal disorders3/3260/324
Urinary tract infectionInfections and infestations0/3262/324
Wound infectionInfections and infestations0/3262/324
SeizureNervous system disorders1/3262/324
Cardiac failureCardiac disorders2/3261/324
Liver injuryHepatobiliary disorders2/3260/324
BacteraemiaInfections and infestations2/3260/324
CellulitisInfections and infestations2/3261/324
Most frequent other events
Showing 10 of 118
Most frequent other events
EventTucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + Pertuzumab
DiarrhoeaGastrointestinal disorders237/326166/324
NauseaGastrointestinal disorders107/32676/324
Alanine aminotransferase increasedInvestigations90/32623/324
Aspartate aminotransferase increasedInvestigations82/32629/324
ArthralgiaMusculoskeletal and connective tissue disorders67/32675/324
FatigueGeneral disorders67/32641/324
VomitingGastrointestinal disorders64/32645/324
PruritusSkin and subcutaneous tissue disorders62/32658/324
HeadacheNervous system disorders61/32657/324
CoughRespiratory, thoracic and mediastinal disorders60/32645/324

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Tucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + PertuzumabTotal
Mean53.2 ± 11.553.2 ± 11.053.2 ± 11.3
Sex: Female, Male
Sex: Female, Male(Participants)Tucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + PertuzumabTotal
Female326328654
Male000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Tucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + PertuzumabTotal
White147147294
Asian119111230
Not reportable394079
Black or African American10919
Other5813
Unknown167
Multiple516
American Indian or Alaska Native044
Native Hawaiian or Other Pacific Islander022
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Tucatinib + Trastuzumab + PertuzumabPlacebo + Trastuzumab + PertuzumabTotal
Not Hispanic, Latino/a, or of Spanish Origin221212433
Hispanic, Latino/a, or of Spanish Origin5571126
Not reportable394180
Unknown11415
08

Study locations

307 sites
  • Mayo Clinic Hospital
    Phoenix, Arizona 85054, United States
  • Mayo Clinic
    Scottsdale, Arizona 85259, United States
  • Central Arkansas Radiation Therapy Institute Inc d.b.a CARTI
    Little Rock, Arkansas 72205, United States
  • UCLA Hematology/Oncology - Beverly Hills
    Beverly Hills, California 90212, United States
  • UCLA Hematology/Oncology - Burbank
    Burbank, California 91505, United States
  • UCSD Medical Center - Encinitas
    Encinitas, California 92024, United States
  • Sulpizio Cardiovascular Center at UC San Diego Health
    La Jolla, California 92037, United States
  • UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
    La Jolla, California 92037, United States
  • UCSD Koman Family Outpatient Pavilion
    La Jolla, California 92037, United States
  • UCSD Perlman Medical Offices
    La Jolla, California 92037, United States
  • UC San Diego Moores Cancer Center
    La Jolla, California 92093, United States
  • UCLA Hematology/Oncology - Laguna Hills
    Laguna Hills, California 92653, United States
  • Administrative Address: UCLA Hematology/Oncology
    Los Angeles, California 90095, United States
  • UCLA Hematology/Oncology
    Los Angeles, California 90095, United States
  • UCSD Medical Center - Bankers Hill
    San Diego, California 912101, United States
  • UC San Diego Medical Center - Hillcrest
    San Diego, California 92103, United States
  • UCLA Hematology/Oncology - San Luis Obispo
    San Luis Obispo, California 93401, United States
  • UCLA Hematology/Oncology- Santa Barbara
    Santa Barbara, California 93101, United States
  • UCLA Hematology/Oncology - Santa Monica
    Santa Monica, California 90404, United States
  • UCLA Hematology/Oncology Parkside
    Santa Monica, California 90404, United States
  • Clinical And Translational Research Center
    Torrance, California 90502, United States
  • The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
    Torrance, California 90502, United States
  • Harbor-UCLA Medical Center
    Torrance, California 90509, United States
  • UCLA Hematology/Oncology - Santa Clarita
    Valencia, California 91355, United States
  • UCSD Medical Center - Vista
    Vista, California 92081, United States
  • UCLA Hematology/Oncology- Westlake
    Westlake Village, California 91361, United States
  • AdventHealth Altamonte Infusion Center
    Altamonte Springs, Florida 32701, United States
  • AdventHealth Medical Group Altamonte(second location)
    Altamonte Springs, Florida 32701, United States
  • AdventHealth Medical Group Altamonte
    Altamonte Springs, Florida 32701, United States
  • Mayo Clinic Florida
    Jacksonville, Florida 32224, United States
  • AdventHealth Medical Group Orlando
    Orlando, Florida 32804, United States
  • AdventHealth Orlando Infusion Center
    Orlando, Florida 32804, United States
  • Emory University Hospital Midtown
    Atlanta, Georgia 30308, United States
  • Emory University Clinic
    Atlanta, Georgia 30322, United States
  • Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Emory Saint Joseph's Hospital
    Atlanta, Georgia 30342, United States
  • University of Illinois Hospital and Health Systems (Investigational Drug Pharmacy)
    Chicago, Illinois 60612, United States
  • University of Illinois Hospital and Health Systems (Outpatient Cancer Center)
    Chicago, Illinois 60612, United States
  • University of Illinois Hospital and Health Systems
    Chicago, Illinois 60612, United States
  • Norton Cancer Institute - Downtown
    Louisville, Kentucky 40202, United States
  • Norton Cancer Institute, Downtown
    Louisville, Kentucky 40202, United States
  • Norton Cancer Institute, St Matthews Campus
    Louisville, Kentucky 40207, United States
  • Norton Cancer Institute, St. Matthews Campus
    Louisville, Kentucky 40207, United States
  • Norton Cancer Institute, Brownsboro Hospital Campus
    Louisville, Kentucky 40241, United States
  • Mercy Medical Center
    Baltimore, Maryland 21202, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Saint Luke's Cancer Institute.
    Kansas City, Missouri 64111, United States
  • Oncology Hematology West PC dba Nebraska Cancer Specialists
    Grand Island, Nebraska 68803, United States
  • Oncology Hematology West, PC dba Nebraska Cancer Specialists - Grand Island
    Grand Island, Nebraska 68803, United States
  • Oncology Hematology West PC dba Nebraska Cancer Specialists
    Omaha, Nebraska 68114, United States
  • Oncology Hematology West PC dba Nebraska Cancer Specialists
    Omaha, Nebraska 68124, United States
  • Oncology Hematology West PC dba Nebraska Cancer Specialists
    Omaha, Nebraska 68130, United States
  • Oncology Hematology West PC dba Nebraska Cancer Specialists
    Papillion, Nebraska 68046, United States
  • RWJBarnabas Health- Jersey City Medical Center
    Jersey City, New Jersey 07302, United States
  • RWJBarnabas Health- Monmouth Medical Center-Southern Campus
    Lakewood, New Jersey 08701, United States
  • RWJBarnabas Health- Cooperman Barnabas Medical Center
    Livingston, New Jersey 07039, United States
  • RWJBarnabas Health- Monmouth Medical Center
    Long Branch, New Jersey 07740, United States
  • Rutgers Cancer Institute of New Jersey
    New Brunswick, New Jersey 08903, United States
  • Newark Beth Israel Medical Center
    Newark, New Jersey 07112, United States
  • RWJBarnabas Health-Robert Wood Johnson University Hospital, Somerset
    Somerville, New Jersey 08876, United States
  • Steeplechase Cancer Center
    Somerville, New Jersey 08876, United States
  • RWJBarnabas Health - Community Medical Center
    Toms River, New Jersey 08755, United States
  • Satellite Infusion Center-Monmouth Medical Center Vantage Point Infusion Center
    West Long Branch, New Jersey 07764, United States
  • Montefiore Einstein Comprehensive Cancer Center
    The Bronx, New York 10461, United States
  • Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
    Cleveland, Ohio 44106, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Cleveland Clinic Cancer Center - Strongsville
    Strongsville, Ohio 44136, United States
  • Asplundh Cancer Pavillion
    Willow Grove, Pennsylvania 19090, United States
  • Tennessee Oncology, PLLC
    Gallatin, Tennessee 37066, United States
  • Tennessee Oncology, PLLC
    Murfreesboro, Tennessee 37129, United States
  • Sarah Cannon Research Institute- Pharmacy
    Nashville, Tennessee 37203, United States
  • Tennessee Oncology, PLLC
    Nashville, Tennessee 37203, United States
  • Tennessee Oncology, PLLC
    Shelbyville, Tennessee 37160, United States
  • Fred Hutchinson Cancer Center
    Seattle, Washington 98109, United States
  • University of Washington Medical Center
    Seattle, Washington 98195, United States
  • Froedtert Hospital/Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • Chris O'Brien Lifehouse
    Camperdown, New South Wales 2050, Australia
  • Macquarie University Clinical Trials Unit.
    Macquarie University, New South Wales 2109, Australia
  • Western Sydney Local Health District (WSLHD), Westmead Hospital
    Westmead, New South Wales 2145, Australia
  • Cancer Research SA
    Adelaide, South Australia 5000, Australia
  • St Andrews Medical Centre
    Adelaide, South Australia 5000, Australia
  • Flinders Medical Centre
    Bedford Park, South Australia 5042, Australia
  • Box Hill Hospital
    Box Hill, Victoria 3128, Australia
  • Austin Health
    Heidelberg, Victoria 3084, Australia
  • St John of God Subiaco Hospital Clinical Trials Unit Bendat Family Comprehensive Cancer Centre
    Subiaco, Washington 6008, Australia
  • Ordination Priv.-Doz. Dr. Michael Hubalek
    Schwaz, Other A-6130, Austria
  • Medizinische Universität Graz
    Graz, A-8010, Austria
  • Medizinische Universitat Graz
    Graz, A-8036, Austria
  • Ordensklinikum Linz GmbH Barmherzige Schwestern
    Linz, A-4010, Austria
  • Medizinische Universitat Wien Universitatsklinik Fur Frauenheilkunde
    Vienna, A-1090, Austria
  • Jules Bordet lnstituut
    Anderlecht, 1070, Belgium
  • Universitair Ziekenhuis Brussel (UZ Brussel)
    Brussels, 1090, Belgium
  • Cliniques Universitaires Saint-Luc
    Brussels, 1200, Belgium
  • Clinique St-Pierre
    Ottignies, 1340, Belgium
  • CRIO - Centro Regional lntegrado de Oncologia
    Fortaleza, Ceará 60336-232, Brazil
  • Hospital Araujo Jorge
    Goiânia, Goiás 74605-070, Brazil
  • A.C. Camargo Câncer Center
    Sao Paulo/SP, Other 01.509-010, Brazil
  • Hospital Do Cancer De Londrina
    Londrina, Paraná 86015-520, Brazil
  • Liga Norte-Rio Grandense Contra o Cancer
    Natal, Rio Grande do Norte 59075-740, Brazil
  • Hospital de Clinicas de Porto Alegre
    Porto Alegre, Rio Grande do Sul 90035-903, Brazil

Showing the first 100 of 307 sites across 23 countries.

09

References and documents

Publications

  • Dieras V, Curigliano G, Martin M, Lerebours F, Tsurutani J, Savard MF, Jerzak KJ, Hu X, Martins de Aquino Pimentel LC, O'Sullivan CC, Tokunaga E, Okines A, Huang CS, Jacot W, Sohn J, Cronemberger Silva E, Mueller V, Yang S, Granata G, Shen Q, Santarpia L, Hamilton E; HER2CLIMB-05 Investigators. HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer. J Clin Oncol. 2026 Jun 10;44(17):1597-1607. doi: 10.1200/JCO-25-02600. Epub 2025 Dec 10. PubMed 41369677 ↗

Study documents

  • Study protocol · Aug 27, 2024
  • Statistical analysis plan · Aug 15, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

10

Updates

1 registry update since Sep 25, 2026
Results
Results posted
posted Sep 29, 2026
Also revised
primary outcomes
Show all 1 update
  1. Sep 29, 2026
    Results posted
    Primary outcomes Revised (2 changes)
    + 4 other changes: identifiers, verification date, secondary outcomes and documents

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT05132582
Lead sponsor
Seagen, a wholly owned subsidiary of Pfizer
Responsible party
Sponsor
First posted
Nov 24, 2021
Start date
Mar 7, 2022
Primary completion
Sep 5, 2025
Completion
Sep 28, 2027 (estimated)
Results posted
Sep 29, 2026
Last update
Sep 29, 2026

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Breast Neoplasms→

Other studies from this sponsor

Seagen, a wholly owned subsidiary of Pfizer

Start the discussion