Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

Key Inclusion Criteria:

1. Male and female, ≥ 18 years
2. Documented advanced or metastatic malignancy
3. Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration over the 2 weeks prior to baseline or day of first dosing
4. All participants must provide a tumour sample for tissue-based analysis
5. At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate Cancer) which allows participants with non measurable bone metastatic disease
6. Adequate bone marrow reserve and organ function
7. Minimum life expectancy of 12 weeks
8. At the time of screening, contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
9. All women of childbearing potential must have a negative serum pregnancy test documented during screening
10. Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control. Female participants must not donate, or retrieve for their own use, ova at any time during this study
11. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile, avoid intercourse, or use a highly effective method of contraception. Male participants must not freeze or donate sperm at any time during this study.
12. Capable of giving signed informed consent
13. Provision of signed and dated written optional genetic research informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative

Key Exclusion Criteria:

1. Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol
2. History of another primary malignancy except for adequately resected basal cell carcinoma or in situ squamous cell carcinoma of the skin, or other solid malignancy treated with curative intent
3. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved
4. Spinal cord compression or brain metastases unless treated
5. Leptomeningeal carcinomatosis
6. Clinically significant corneal disease
7. Active hepatitis or uncontrolled hepatitis B or C virus infection
8. Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for example prodromal symptoms
9. Known HIV infection that is not well controlled
10. Active TB infection
11. Significant cardiac diseases
12. History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required steroids
13. Has severe pulmonary function compromise
14. Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period
15. Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention
16. Prior exposure to anticancer therapies without an adequate treatment washout period prior to enrolment or any concurrent anticancer treatment
17. Major surgical procedure or significant traumatic injury within ≤ 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study
18. Prior treatment with TROP2-directed Anti-drug antibody, ADC Antibody-drug conjugate (ADCs), other ADCs with deruxtecan payload
19. Severe hypersensitivity to monoclonal antibodies
20. Pregnant, breastfeeding, planning to become pregnant