This study investigates the effects of an investigational medication combined with chemotherapy in patients with advanced HER2-positive breast cancer. HER2-positive means that the cancer cells have more HER2 receptors than normal, which can promote the growth of cancer cells. The study compares the progression-free survival and overall survival of patients receiving this combination to those receiving another treatment with chemotherapy.

Participants will either receive the investigational medication plus chemotherapy or an alternative treatment plus chemotherapy. Progression-free survival refers to the length of time during and after treatment that a patient lives with the disease without it getting worse. Overall survival refers to the duration a patient lives from the start of the study, regardless of disease status.

• Who can participate: Adults with advanced HER2-positive breast cancer who have received at least two prior anti-HER2 therapies in a metastatic setting may join. If they have had (neo)adjuvant pertuzumab, they need at least one prior anti-HER2 therapy in the metastatic setting.
• Study details: Participants will receive either the investigational medication with chemotherapy or trastuzumab with chemotherapy. A placebo is not used in this study. Participants should have received no more than three lines of therapy overall in the metastatic setting.