TUGETHER: This study is evaluating the effectiveness of targeted therapy (tucatinib) in combination with other cancer therapies (immunotherapy, targeted therapy and chemotherapy) in people with HER2-positive, metastatic breast cancer who have progressed on previous treatmentA Phase II, Two-arm, Non-comparative, Multicentre Study of Tucatinib (ONT-380), Pembrolizumab and Trastuzumab in Patients With Pre-treated Advanced HER2-positive Breast Cancer

Summary

Eligible participants will be assigned to one of two experimental arms, depending on whether their disease is PD-L1 positive or PD-L1 negative. Participants who are PD-L1 positive will receive targeted therapy (tucatinib + trastuzumab) plus immunotherapy (pembrolizumab). Participants who are PD-L1 negative will receive targeted therapy (tucatinib + trastuzumab) plus immunotherapy (pembrolizumab) plus chemotherapy (capecitabine). Chemotherapy will be given to these participants as the researchers believe this will overcome the lower immunogenicity of the cohort. In both groups, treatment cycles are 21 days. Tucatinib will be given orally twice daily, every day, at a dose of 300mg. Pembrolizumab will be administered at a dose of 200mg via intravenous infusion (IV) on Day 1 of each cycle. Trastuzumab will be given as a loading dose of 8mg/kg via IV (if loading is required, otherwise 6mg/kg) on day 1 followed by 6mg/kg on day 1 of each cycle. For those receiving chemotherapy, capecitabine will be given orally at a dose of 1000mg/m^2 twice daily on days 1-14 of each cycle.