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A Study of Tucatinib or Place...

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

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

654 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-07

Study Completion Date

2027-09-28

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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HER2 Positive Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tucatinib + trastuzumab + pertuzumab

Group Type EXPERIMENTAL

Tucatinib

Intervention Type DRUG

300mg given by mouth (orally) twice daily

Trastuzumab

Intervention Type DRUG

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

Pertuzumab

Intervention Type DRUG

420mg given by IV every 21 days

Combination product: Trastuzumab + Pertuzumab

Intervention Type DRUG

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.

Placebo + trastuzumab + pertuzumab

Group Type ACTIVE_COMPARATOR

Trastuzumab

Intervention Type DRUG

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

Pertuzumab

Intervention Type DRUG

420mg given by IV every 21 days

Combination product: Trastuzumab + Pertuzumab

Intervention Type DRUG

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.

Placebo

Intervention Type DRUG

Given orally twice daily

Interventions

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Tucatinib

300mg given by mouth (orally) twice daily

Intervention Type DRUG

Trastuzumab

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

Intervention Type DRUG

Pertuzumab

420mg given by IV every 21 days

Intervention Type DRUG

Combination 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.

Intervention Type DRUG

Placebo

Given orally twice daily

Intervention Type DRUG

Other Intervention Names

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TUKYSA, ONT-380, ARRY-380 Herceptin, Herceptin Hylecta Perjeta Phesgo

Eligibility Criteria

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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

* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Meizhou People's Hospital

Meizhou, Guangdong, China

Site Status

Liuzhou People's Hospital

Liuchow, Guangxi, China

Site Status

Chang Gung Memorial Hospital LinKou

Taoyuan, , Taiwan

Site Status

Academic Oncology

London, England, United Kingdom

Site Status

The Royal Marsden

Sutton, Surrey, United Kingdom

Site Status

Finchley Memorial Hospital

London, , United Kingdom

Site Status

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

Central Arkansas Radiation Therapy Institute Inc d.b.a CARTI

Little Rock, Arkansas, United States

Site Status

UCLA Hematology/Oncology - Beverly Hills

Beverly Hills, California, United States

Site Status

UCLA Hematology/Oncology - Burbank

Burbank, California, United States

Site Status