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A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)

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ClinicalTrials.gov Identifier: NCT05132582
Recruitment Status : Recruiting
First Posted : November 24, 2021
Last Update Posted : April 23, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Seagen Inc.

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
HER2 Positive Breast Cancer Drug: Tucatinib Drug: Trastuzumab Drug: Pertuzumab Drug: Combination product: Trastuzumab + Pertuzumab Drug: Placebo Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 650 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : March 7, 2022
Estimated Primary Completion Date : October 31, 2024
Estimated Study Completion Date : June 30, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tucatinib + trastuzumab + pertuzumab
Tucatinib + trastuzumab + pertuzumab
 Drug: Tucatinib
300mg given by mouth (orally) twice daily
Other Name: TUKYSA, ONT-380, ARRY-380

Drug: Trastuzumab
6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days
Other Name: Herceptin, Herceptin Hylecta

Drug: Pertuzumab
420mg given by IV every 21 days
Other Name: Perjeta

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.
Other Name: Phesgo
Active Comparator: Placebo + trastuzumab + pertuzumab
Placebo + trastuzumab + pertuzumab
 Drug: Trastuzumab
6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days
Other Name: Herceptin, Herceptin Hylecta

Drug: Pertuzumab
420mg given by IV every 21 days
Other Name: Perjeta

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.
Other Name: Phesgo

Drug: Placebo
Given orally twice daily


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to approximately 3 years ]
    The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to approximately 5 years ]
    The time from randomization to death from any cause.

  2. PFS by blinded independent central review (BICR) per RECIST v1.1 [ Time Frame: Up to approximately 3 years ]
    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

  3. Time to deterioration of health-related quality of life (HRQoL) [ Time Frame: Up to approximately 3 years ]
    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).

  4. Central nervous system (CNS) PFS [ Time Frame: Up to approximately 3 years ]
    The time from randomization to investigator assessed disease progression in brain (RECIST v1.1), or death from any cause

  5. Incidence of adverse events (AEs) [ Time Frame: Through 30 days after last study treatment, approximately 18 months ]
    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.

  6. Incidence of laboratory abnormalities [ Time Frame: Through 30 days after last study treatment, approximately 18 months ]
    To be summarized using descriptive statistics.

  7. Incidence of tucatinib dose alterations [ Time Frame: Through 30 days after last study treatment, approximately 18 months ]
    To be summarized using descriptive statistics.

  8. Incidence of trastuzumab dose alterations [ Time Frame: Through 30 days after last study treatment, approximately 18 months ]
    To be summarized using descriptive statistics.

  9. Incidence of pertuzumab dose alterations [ Time Frame: Through 30 days after last study treatment, approximately 18 months ]
    To be summarized using descriptive statistics.

  10. Maximum concentration (Cmax) [ Time Frame: Through 30 days after last study treatment, approximately 18 months ]
    To be summarized using descriptive statistics.

  11. Trough concentration (Ctrough) [ Time Frame: Through 30 days after last study treatment, approximately 18 months ]
    To be summarized using descriptive statistics.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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+ 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05132582


Contacts
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Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
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Sponsors and Collaborators
Seagen Inc.
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Monitor Seagen Inc.
More Information
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Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT05132582    
Other Study ID Numbers: SGNTUC-028
First Posted: November 24, 2021    Key Record Dates
Last Update Posted: April 23, 2024
Last Verified: April 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
HER2+ breast cancer
Breast Cancer
Metastatic breast cancer
Seattle Genetics
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Pertuzumab
 Tucatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action