• Participants must have at least one measurable lesion as defined by RECIST v1.1.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.

• Life expectancy of at least 3 months

• Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible which do not constitute a safety risk by Investigator judgment

⁃ MBC substudy:

• Histologically confirmed invasive HER2 positive breast cancer

• Available tumor tissue (FFPE slides or block). A fresh biopsy is preferred but optional.

• Received at least one prior line of therapy including T-DXd for locally advanced/metastatic HER2 positive breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease.

• Progressed on or following the most recent line of therapy

• Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine)

• LVEF ≥50%

• Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockroft-Gault equation

• Adequate liver function:

• Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome);

• Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease).