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Clinical Trial Details

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Molecule overview Clinical trials

Breast Cancer

Tucatinib

A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)

Phase 3

NCT05132582

Active Not-enrolling

Locations

United States, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, Finland, France, Germany, Greece, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Spain, Switzerland, Taiwan, United Kingdom

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Study design Key eligibility criteria Key dates Key endpoints Number of participants Collaborators and investigators

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Study design

Participant Group/Arm

EXPERIMENTAL: Tucatinib + trastuzumab + pertuzumab

Tucatinib + trastuzumab + pertuzumab

Intervention/Treatment

DRUG: Tucatinib

300mg given by mouth (orally) twice daily

DRUG: Trastuzumab

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

DRUG: Pertuzumab

420mg given by IV every 21 days

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.

Participant Group/Arm

ACTIVE_COMPARATOR: Placebo + trastuzumab + pertuzumab

Placebo + trastuzumab + pertuzumab

Intervention/Treatment

DRUG: Trastuzumab

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

DRUG: Pertuzumab

420mg given by IV every 21 days

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.

DRUG: Placebo

Given orally twice daily

Study design table for Clinical Trial

Key eligibility criteria

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+ diseas
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
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 sympto

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

Key dates

Study start date

March 2022

Estimated primary completion date

October 2027

Key endpoints

Primary Outcome Measures

Outcome Measure

Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Measure Description

The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause

Time Frame

Up to approximately 3 years

Primary Outcome Measures table for Clinical Trial

Secondary Outcome Measures:

Outcome Measure

Overall survival (OS)

Measure Description

The time from randomization to death from any cause.

Time Frame

Up to approximately 5 years

Outcome Measure

PFS by blinded independent central review (BICR) per RECIST v1.1

Measure Description

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

Time Frame

Up to approximately 3 years

Outcome Measure

Time to deterioration of health-related quality of life (HRQoL)

Measure Description

Will be measured based on patient reported outcomes (PROs) according to the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30).

Time Frame

Up to approximately 3 years

Outcome Measure

Central nervous system (CNS) PFS

Measure Description

The time from randomization to investigator assessed disease progression in brain (RECIST v1.1), or death from any cause

Time Frame

Up to approximately 3 years

Outcome Measure

Incidence of adverse events (AEs)

Measure Description

Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.