TUGETHER / BCT 2102

Women or men with HER2-positive, metastatic breast cancer, who have progressed on previous treatment, will receive tucatinib in combination with pembrolizumab and trastuzumab (PD-L1 positive).

Despite significant advances in systemic treatment options, advanced HER2-positive breast cancer post treatment with trastuzumab, pertuzumab and T-DM1 still remains incurable, with brain metastases remaining a major cause of patient morbidity and mortality.

HER2-positive breast cancers have relatively high tumour infiltrating lymphocytes (TILs) that may be targeted with immune checkpoint blockade. Studies in metastatic breast cancer with PD1 or PD-L1 inhibition have shown an overall survival (OS) benefit for those that are enriched for pre-existing immunity, such as positive expression of PD-L1 protein or TILs present.

One of the main areas of disease progression in HER2 positive disease is in the central nervous system (CNS), supporting the need to find an effective combination for patients with brain metastases.

Tucatinib (ONT-380) is a potent, highly selective, oral HER2 small molecule tyrosine kinase inhibitor (TKI) with demonstrated clinical benefit notable for its minimal inducement of EGFR-type toxicities when administered in combination-type studies including proven intra-cranial efficacy in studies of patients with brain metastases.