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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Objective response rate (ORR)

Primary Outcome 1 - Timeframe: From baseline to progressive disease or death (approximately 1 year)

Primary Outcome 2 - Measure: The number of subjects with adverse events/serious adverse events

Primary Outcome 2 - Timeframe: Throughout the treatment and the safety follow-up period 28 [+ 7] days after the discontinuation of all study interventions, except durvalumab, nivolumab, and bevacizumab for which it will be 90 [+ 7] days (approximatelt 1 year)

Primary Outcome 3 - Measure: PSA50 response (Substudy 3 only)

Primary Outcome 3 - Timeframe: Time to PSA progression is defined as the time from randomization to PSA progression per PCWG3 criteria (up to 12 weeks)

CONDITION

• Endometrial Cancer
• Gastric Cancer
• Metastatic Castration-resistant Prostate Cancer
• Ovarian Cancer
• Colorectal Cancer
• Urothelial Cancer
• Biliary Tract Cancer

ELIGIBILITY

Key Inclusion Criteria:
* Male and female, ≥ 18 years

- * Documented advanced or metastatic malignancy

- * 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

- * All participants must provide a tumour sample for tissue-based analysis

- * At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate Cancer) which allows participants with non measurable bone metastatic disease

- * Adequate bone marrow reserve and organ function

- * Minimum life expectancy of 12 weeks

- * 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

- * All women of childbearing potential must have a negative serum pregnancy test documented during screening

- * 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

- * 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.

- * Capable of giving signed informed consent

- * 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:
* 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

- * 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

- * Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved

- * Spinal cord compression or brain metastases unless treated

- * Leptomeningeal carcinomatosis

- * Clinically significant corneal disease

- * Active hepatitis or uncontrolled hepatitis B or C virus infection

- * Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for example prodromal symptoms

- * Known HIV infection that is not well controlled

- * Active TB infection

- * Significant cardiac diseases

- * History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required steroids

- * Has severe pulmonary function compromise

- * Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period

- * Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention

- * Prior exposure to anticancer therapies without an adequate treatment washout period prior to enrolment or any concurrent anticancer treatment

- * 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

- * Prior treatment with TROP2-directed Anti-drug antibody, ADC Antibody-drug conjugate (ADCs), other ADCs with deruxtecan payload

- * Severe hypersensitivity to monoclonal antibodies

- * Pregnant, breastfeeding, planning to become pregnant

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Global Clinical Lead, MD

Role: Principal Investigator

Affiliation: AstraZeneca

Overall Contact

Name: Global Clinical Lead, MD

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

LOCATION