SHS_492319 WAHL CONT 15263

Phase 2 Randomized, Double-Blinded, Controlled Study of ONT-380 vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma

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.

Select Inclusion Criteria (see for more information):

Histologically confirmed HER2+ breast carcinoma.
Received previous treatment with a taxane, trastuzumab, pertuzumab, and T-DM1 (with more specific requirements dependent upon treatment).
Progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy.
Have measurable or non-measureable disease assessable by RECIST 1.1 and/or RANO-BM criteria
Be at least 18 years of age at time of consent
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
Life expectancy of at least 6 months, in the opinion of the investigator
Adequate hepatic function.
Adequate baseline hematological parameters (specifics values listed).
Have left ventricular ejection fraction (LVEF) ≥ 50% documented within 4 weeks prior to first dose of study treatment.
Based on screening brain magnetic resonance imaging (MRI), patients must have no evidence of CNS metastases OR untreated CNS metastases not needing immediate local therapy, where all untreated CNS lesions are ≤ 2.0 cm on screening MRI OR previously treated CNS metastases
For patients treated with CNS local therapy screening brain MRI must show no increase in any lesion of > 10 mm.
Patients treated with CNS local therapy for newly identified lesions may be eligible to enroll if time since WBRT is > 21 days prior to first dose of treatment AND time since stereotactic radiosurgery (SRS) is > 14 days prior to first dose of treatment OR time since surgical resection is > 28 days.
Non-CNS sites of evaluable disease are present.

Select Exclusion Criteria (see for more information):

Previously been treated with either lapatinib, neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 TKI.
Previously been treated with capecitabine.
History of exposure to the following cumulative doses of anthracyclines (specifics are listed).
History of allergic reactions to trastuzumab, capecitabine, or ONT-380 (or compounds chemically or biologically similar), except for Grade 1 or 2 infusion related reactions to trastuzumab that were successfully managed.
Received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, or experimental agent ≤ 3 weeks of first dose of study treatment.
Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with exceptions listed.
Clinically significant cardiac disease.
Known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment.
Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease.
Are known to be positive for human immunodeficiency virus (HIV).
Require warfarin therapy.
Inability to swallow pills or any significant gastrointestinal disease that would preclude the adequate oral absorption of medications.
Used a strong CYP3A4 inducer or inhibitor, or strong CYP2C8 inducer or inhibitor within 3 elimination half-lives of the inhibitor or inducer prior to first dose of study treatment.
Have known dihydropyrimidine dehydrogenase deficiency.
Unable for any reason to undergo MRI of the brain.
Based on screening brain MRI, patients must not have any untreated lesions > 2.0 cm in size.
Ongoing use of systemic corticosteroids <28 days prior to first dose of study treatment.
Known leptomeningeal disease (LMD).
Poorly controlled seizures.
Phase II
Tanya Wahl, M.D.
Cascadian Therapeutics (formerly Oncothyreon)
Shaula Levy
  • Swedish Medical Center