The goal of this clinical trial is to test a new medicine called GSK5764227, which delivers a toxin directly to cancer cells to destroy them while sparing healthy cells. The study will combine GSK5764227 with standard treatments to evaluate its safety, examine how the body processes it, check if it triggers any immune responses, and assess whether it can shrink or control cancer.

Inclusion Criteria:

• Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
• Has adequate organ function.
• Has histologically confirmed unresectable adenocarcinoma or unresectable metastatic adenocarcinoma of the colon or rectum. (Cohort A)
• Histologically or cytologically confirmed adenocarcinoma of the prostate (Cohort B)

Exclusion Criteria:

• Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] that have been resected with no evidence of disease.
• Has had any major surgery within 28 days prior to first dose.
• Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
• Has serious infection within 4 weeks prior to the first dose,
• Has untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
• Any evidence of current interstitial lung disease (ILD) or pneumonitis OR a prior history of ILD requiring high-dose glucocorticoids or non-infectious pneumonitis requiring high-dose glucocorticoids.
• Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening.
• Has received immunosuppressive agents within 30 days prior to first dose of study intervention (or requires long-term [30 days or longer]). Low-dose corticosteroids (prednisone ≤10 milligrams (mg)/day or equivalent) may be administered.

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.