This is a single arm, open label trial to assess the safety and efficacy of tucatinib in
combination with pembrolizumab and trastuzumab for the treatment of HER2+ breast cancer brain
metastases (BCBM). A total of 33 patients with untreated or previously treated and
progressing HER2+ BCBM not requiring urgent central nervous system (CNS)-directed therapy
will be enrolled. The study will determine the recommended dose of tucatinib in this
combination and assess the efficacy of this combination in controlling CNS disease in
patients with HER2+ BCBM.
Inclusion Criteria:
1. Age ≥18 years.
2. ECOG performance status of 0-2.
3. HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer.
4. Untreated or previously treated and progressing CNS disease.
5. Measurable CNS metastases.
6. Must be able to undergo MRI of the brain.
7. Adequate organ function.
Exclusion Criteria:
1. Any indication for immediate CNS-directed therapy.
2. History of generalized or complex partial seizures.
3. Any other manifestation of neurologic progression that in the opinion of the treating
physician is due to brain metastases.
4. Leptomeningeal disease.
5. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor.
6. Prior therapy with tucatinib.
7. Active autoimmune disease that has required systemic treatment in excess of prednisone
10mg daily or equivalent in the past 2 years.
Complete inclusion/exclusion criteria are detailed in the protocol.
