Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs. Placebo in Combination with Capecitabine and Trastuzumab in Patients with Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma

Description: The purpose of this study is to assess the effect of ONT-380 vs. placebo in combination with capecitabine and trastuzumab on both central nervous system (CNS) and non-CNS progression-free survival (PFS) based on independent central review.

Inclusion Criteria:
Patients must meet the following criteria to be eligible for the study:
• Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by fluorescence in situ hybridization (FISH) and/or 3+ staining by immunohistochemistry (IHC) a. Tissue blocks or slides must be submitted to confirm HER2 positivity (FISH-positive or IHC 3+) by a sponsor-designated central laboratory prior to randomization. Centrally confirmed HER2 results (either IHC or FISH) from a previous study can be used to determine eligibility for this study with approval from the sponsor.
• Have received previous treatment with a taxane, trastuzumab, pertuzumab, and T-DM1
• Have one of the following:
-If both pertuzumab and T-DM1 were administered for metastatic or locally advanced unresectable breast cancer, must be at least 6 months since diagnosis of metastatic or locally advanced unresectable breast cancer.
-If either pertuzumab or T-DM1 was administered in the neo-adjuvant or adjuvant setting (and the other administered for metastatic or locally advanced unresectable breast cancer), must be at least 3 months since diagnosis of metastatic or locally advanced unresectable breast cancer.
-If both pertuzumab and T-DM1 were administered in the neo-adjuvant or adjuvant setting, must have completed adjuvant treatment at least 12 months prior to enrollment.
• Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator).

Exclusion Criteria:
• Previously been treated with:
-lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or toxicity)
-neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) at any time previously
-previously been treated with capecitabine for metastatic disease except in cases where capecitabine was given for < 21 days and was discontinued for reasons other than disease progression or toxicity. Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.
• Clinically significant cardiopulmonary disease
• Unable for any reason to undergo MRI of the brain
• CNS Exclusion - Based on screening brain MRI, patients must not have any of the following:
-Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor
-Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)
-Any brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria
-Known or concurrent leptomeningeal disease (LMD)
-Poorly controlled seizures

Location:

• Oncology and Hematology Care Westside
• Providence Cancer Institute Clackamas Clinic
• Providence Cancer Institute Franz Clinic
• Providence Cancer Institute Newberg Clinic