HER2CLIMB-05: This phase III study is trying to understand whether targeted therapy (tucatinib) works better than placebo when given with other drugs (trastuzumab and pertuzumab) to treat people with HER2-positive breast cancer.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)

Inclusion

• 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