A Study of Subcutaneous Trastuzumab Deruxtecan in Participants With Metastatic Solid Tumors.

Key Inclusion Criteria:

1. Adults ≥18 years or the minimum legal adult age (whichever is greater).

2. a) Disease State: If HER2 status is required for eligibility (for all populations), a documented HER2 test result must be available.

   Breast Cancer: adults with pathologically documented unresectable or metastatic breast cancer HER2-positive BC: have received a prior anti-HER2-based regimen. For HER2-positive BC participants in Part 2 only, prior anti-HER2 based therapy should have been received in either:

   • the metastatic setting, or

   • the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. HR-, HER2-low BC: have received a prior systemic cytotoxic therapy in the metastatic setting; or developed disease recurrence during or within 6 months of completing (neo)adjuvant chemotherapy. HR+, HER2-low/ultralow BC: have received previous ET AND an additional line of ET must not be the next line of treatment considered in the participant's best interest.

   • For participants in Part 2 with HR+ HER-2low/ultralow BC, the following criteria also apply:

   • had disease progression while receiving 1 previous line of ET with a CDK4/6i and is not expected to benefit from immediate use of a second line of ET, OR

   • had disease progression on at least 2 previous lines of ET with or without a target therapy such as CDK4/6, mTOR or PI3-K inhibitors) administered for the treatment of metastatic disease

   • participants may not have received more than 2 prior lines of cytotoxic therapy in the recurrent or metastatic setting. NSCLC, HER2 mut: adults with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and who have received a prior systemic therapy.

     b) Part 2 only: At least 1 RECIST 1.1 measurable lesion on CT or MRI.

3. Radiologic or objective evidence of disease progression on or after the last systemic therapy prior to starting trial intervention.