Unresectable Locally-Advanced or Metastatic HER2+ Breast Cancer
Conditions
Interventions
Japan Specific Safety Run-in: receive tucatinib 300 mg orally (PO) twice a day (BID) and T-DM1 3.6 mg per kg intravenously (IV) every 21 days.
Randomized Study: Control arm: Placebo given PO BID
T-DM1 3.6 mg per kg given intravenously (IV) every 21 days, Experimental arm: Tucatinib 300 mg PO BID
T-DM1 3.6 mg per kg IV every 21 days
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed HER2+ metastatic breast carcinoma as determined by a sponsor-designated central laboratory 2. History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination 3. Have progression of unresectable LA or M breast cancer after last systemic therapy, or be intolerant of last systemic therapy 4. Measurable or non-measurable disease assessable by RECIST v1.1 5. Hormone receptor (estrogen receptor or progesterone receptor) status must be known prior to randomization 6. ECOG performance status score of 0 or 1 7. Life expectancy greater than or equal to 6 months 8. CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), subjects must have at least one of the following: (a) No evidence of brain metastases (b) Untreated brain metastases not needing immediate local therapy (c) Previously treated brain metastases c-1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy c-2. Subjects treated with CNS local therapy for newly identified lesions may be eligible to enroll if all of the following criteria are met: (i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 14 days prior to first dose, or time since surgical resection is at least 28 days. (ii) Other sites of evaluable disease are present 3.Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
Exclusion criteria
Exclusion criteria: 1. Prior treatment with tucatinib, neratinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for less than 21 days and was discontinued for reasons other than disease progression or severe toxicity). 2. Prior treatment with T-DM1 3. Treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, experimental agent or participation in another interventional clinical trial less than or equal to 3 weeks prior to first dose of study treatment 4. Any toxicity related to prior cancer therapies that has not resolved to less than or equal to Grade 1, with the following exceptions: a.Alopecia; b.Neuropathy, which must have resolved to less than or equal to Grade 2; c.Congestive heart failure (CHF), which must have been less than or equal to Grade 1 in severity at the time of occurrence, and must have resolved completely 5. Clinically significant cardiopulmonary disease 6. Myocardial infarction or unstable angina within 6 months prior to first dose of study treatment 7. Positive for Hepatitis B by surface antigen expression, positive for Hepatitis C infection, or the presence of known chronic liver disease. Subjects who have been treated for Hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks. As reactivation of these viruses has not been studied with tucatinib or T-DM1, there is a possible risk of reactivation. 8. Positive for human immunodeficiency virus (HIV) 9. Subjects who are pregnant, breastfeeding, or planning to become pregnant from time of informed consent until 7 months following the last dose of study drug 10. Unable to swallow pills or has significant gastrointestinal disease which would preclude the adequate oral absorption of medications 11. Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of study treatment 12. CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), subjects must not have any of the following: a. Any untreated brain lesions more than 2 cm in size b. Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of more than 2 mg of dexamethasone (or equivalent). c. Any brain lesion thought to require immediate local therapy d. Known or concurrent leptomeningeal disease as documented by the investigator e. Poorly controlled generalized or complex partial seizures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Japan Specific Safety Run-in: Type, incidence, relatedness, severity, and seriousness of AEs including dose limiting toxicities (DLTs), Type, incidence and severity of laboratory abnormalities, Treatment discontinuation rate due to AEs Randomized Study: PFS per RECIST v1.1, as determined by investigator assessment | — |
Countries
Australia, Austria, Belgium, Canada, China, Denmark, France, Germany, Israel, Italy, Japan, Netherlands, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed