A Study of GSK5733584 in Combination With Anti-cancer Therapies for Advanced Solid Tumors

Inclusion Criteria:

• Participants must be 18 years of age inclusive or older, at the time of signing theinformed consent, or the legal age of consent in the jurisdiction in which the studyis taking place.

• Participant capable of giving signed informed consent including compliance with therequirements and restrictions listed in the Informed consent form (ICF) and in thisprotocol.

• Participants with pathologically confirmed advanced solid tumor specific for studyarms (key local diagnostic molecular and/or immunophenotyping testing results/tumorcell phenotype results for confirmed diagnosis should be provided) who have failedin adequate standard treatments, do not have effective standard treatment or areintolerant to standard of care, with no more than 4 lines of prior systemictherapies.

• Requirements for tumor tissue samples: Archival or fresh tumor tissue is requiredfor retrospective central assessment of B7H4 expression by IHC and other biomarkeranalysis. The archival tumor tissue should be from the most recent procedure (ideally obtained after the last anti-cancer treatment). If an archival tissue isnot available a new biopsy should be performed, and the newly obtained tissueprovided.

• Participants have at least one target lesion as assessed per the RECIST 1.1. Atarget lesion is defined as a measurable lesion that has not undergone locoregionaltreatment such as irradiation or that has unequivocal progression followinglocoregional treatment, with the longest diameter of ≥ 10 mm at baseline (for lymphnode lesions, the short axis should be ≥ 15 mm).

• Participants have a life expectancy of at least 12 weeks.

• Participants willing to use adequate contraception.

• Male participants:

• Male participants are eligible to participate if they agree to the followingduring the study intervention period and for at least 6 months after the lastdose of study intervention:

• Refrain from donating sperm.

• Female participants:

A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

• Is a Woman of non-childbearing potential (WONCBP) OR

• Is a Woman of childbearing potential (WOCBP) and using a contraceptive method thatis highly effective

• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum asrequired by local regulations) within 24 hours before the first dose of studyintervention

• Has an ECOG performance status of 0 to 1.

• Participants with normal organ and bone marrow function

Exclusion Criteria:

• Has a second malignancy (except disease under study) that has progressed or requiredactive treatment within the past 24 months except for basal cell or squamous cellcarcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] thathave been resected with no evidence of metastatic disease.

• Has any history of prior allogenic or autologous bone marrow transplant or othersolid organ transplant.

• Has known sensitivity to study intervention components, GSK5733584 (antibody-drugconjugate, antibody, free cytotoxin GSK5757810) and combination partner, or itsexcipients or other allergy that, in the opinion of the investigator,contraindicates participation in the study.

• Has any following cardiological examination abnormality:

1. history in prior year of clinically significant or uncontrolled cardiacdisease, acute myocardial infarction, or clinically significant arrhythmia notcontrolled by standard of care therapy.

2. Corrected QT Interval (QTcF) >450 msec or QTcF >480 msec for participants withbundle branch block

• Any evidence of current interstitial lung disease (ILD) or pneumonitis or a priorhistory of ILD or non-infectious pneumonitis.

• Has a history of autoimmune disease that has required systemic treatments in the 2years prior to screening (i.e., with use of disease modifying agents,corticosteroids, or immunosuppressive drugs). Replacement therapy is not considereda form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis orinsulin is not exclusionary).

• Clinically significant bleeding symptoms, significant bleeding tendency, or bleedingtumors within 1 month prior to the first dose of study treatment.

• Serious or poorly controlled hypertension, including history of hypertensive crisis,hypertensive encephalopathy; adjustment of antihypertensive medications due to poorblood pressure control within 2 weeks prior to the first dose of study treatment;systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg duringscreening period.

• Has any active renal condition (e.g., infection, requirement for dialysis, or anyother active significant renal condition or dehydrated condition that could affectthe participant's safety).

• Participants with known history of Human immunodeficiency virus (HIV).

• Has an Alanine transaminase (ALT) value >2.5x Upper Limit of Normal (ULN) and forparticipants with documented liver metastases/tumor infiltration has an ALT value >5x ULN.

• Has a total bilirubin value >1.5x ULN.

• Has received treatment with any cytotoxic chemotherapy drugs or other anti-tumordrugs (including endocrine therapy, molecular targeted therapy, immunotherapy,biotherapy, and investigational drug) within 30 days or 5 half-lives of a medicinalproduct prior to the first dose of study drug; or need to continue these drugsduring the study.

• Use strong inhibitors or inducers of CYP3A4, CYP2D6, P-gp, or breast cancerresistance protein (BCRP) with narrow therapeutic window within 14 days prior to thefirst dose of study drug; or in need of continuing treatment with these drugs duringthe study.

• Have received locoregional radiation therapy within 2 weeks prior to the first doseof study drug; more than 30% of bone marrow irradiation or wide-field radiationtherapy within 4 weeks prior to the first dose of study treatment.