A Study of Dato-DXd in Participants With Solid Tumors [TROPION-PanTumor04 (TP04)]

Prior treatment

• Has unresolved toxicities from previous anticancer therapy.
• Live vaccines within 30 days before the first dose of treatment.

Other illness

• Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients.
• Has uncontrolled or significant cardiovascular disease.
• Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis, including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected interstitial lung disease (ILD)/pneumonitis that cannot be ruled out by imaging at screening.
• Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
• Has clinically significant corneal disease.
• Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
• Has active or uncontrolled HIV infection.
• Has active or uncontrolled hepatitis B or C virus infection.

Other

• Has spinal cord compression or clinically active central nervous system (CNS) metastases.
• Female participants who are pregnant or breastfeeding or intend to become pregnant.

• Must consent to provide archival tumor tissue sample or newly obtained pretreatment biopsy if clinically feasible and at an acceptable risk as determined by the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 assessed no more than 14 days prior to Cycle 1 Day 1 (C1D1) (randomization for randomized cohort).
• Has adequate organ and bone marrow function as assessed by local laboratory within 7 days prior to C1D1 (randomization for randomized cohort) as defined in the protocol.
• Has a left ventricular ejection fraction (LVEF) ≥50 percent (%) by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) scan within 28 days before C1D1 (randomization for randomized cohort).
• Has a life expectancy ≥3 months based on investigator's assessment.
• Female participants must not be pregnant, does not plan to breastfeed during the trial intervention period, agrees to adhere to a contraceptive method that is highly effective and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the intervention period.
• Male participants who intend to be sexually active with a female partner of childbearing potential should use additional barrier methods of contraception or avoid intercourse. Male participants must not freeze or donate sperm at any time during this study.