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) with no more than 4 lines of prior systemic therapies. Please note:

1. Adjuvant +/- neoadjuvant considered one line of therapy

2. Maintenance therapy will be considered as part of the preceding line of therapy (i.e., not counted independently)

3. Unplanned addition or switching to a new drug in a different class isconsidered a separate line of therapy. If an agent in a regimen is switched toanother agent in the same class due to toxicity or intolerance (e.g.hypersensitivity reaction) this is considered part of the same line (i.e. notcounted independently).

• Requirements for tumor tissue samples: Archival or fresh tumor tissue is requiredfor retrospective central assessment of B7H4 expression by immunohistochemistry (IHC) and other biomarker analysis. The archival tumor tissue should be from themost recent procedure (ideally obtained after the last anti-cancer treatment). If anarchival tissue is not available a new biopsy should be performed, and the newlyobtained tissue provided.

• Participants have at least one target lesion as assessed per RECIST 1.1. A targetlesion 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 millimeter (mm) atBaseline (for lymph node lesions, the short axis should be ≥ 15 mm).

• Participants have a life expectancy of at least 12 weeks per investigator assessmentbased on disease burden and extent of supportive care needed.

Inclusion criteria of participants under arm Module 1 (GSK5733584 +/- Dostarlimab) Endometrial Cancer Part A:

a. Participants with histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer who have failed in adequate standard treatments, do not have effective standard treatment or are intolerant to standard of care, and who are not candidates for further curative external radiotherapy or brachytherapy.

Inclusion criteria of participants under arm Module 1 (GSK5733584 +/- Dostarlimab) Endometrial Cancer Part B:

1. Diagnosis of endometrial cancer with confirmed mismatch repair proficient (MMRp) ormicrosatellites stable (MSS) tumor status by local test.

2. Participants who have progressed on or are intolerant to at least 1 line of standardprior systemic therapy (including neoadjuvant or adjuvant as prior line), and whoare not candidates for curative external radiotherapy or brachytherapy. Maintenancetherapy will be considered part of the preceding line of therapy (i.e, not countedindependently).

3. Participants naïve to anti-programmed death protein 1 and/or programmed death ligand 1 (PD[L]-1) anti-cancer therapy.

Inclusion criteria of participants under arm Module 2 (GSK5733584 +/- Bevacizumab) Ovarian Cancer Part A:

a. Participants with histologically or cytologically confirmed advanced epithelial ovarian cancer/fallopian tube/peritoneal cancer (any epithelial histology - mucinous, clear cell, carcinosarcoma, high/low grade serous, endometrioid) who have failed in adequate standard treatments, do not have effective standard treatment or are intolerant to standard of care.

Inclusion criteria of participants under arm Module 2 (GSK5733584 +/- Bevacizumab) Ovarian Cancer Part B:

1. Participants whose advanced ovarian cancer/fallopian tube/peritoneal cancer hasrelapsed more than 6 months from the last dose of platinum before enrollment, i.e.,platinum sensitive.

2. Participants who have progressed on or are intolerant to at least 1 line of standardprior lines of chemotherapy and are not candidates for second cytoreductive surgery.

• Participants willing to use adequate contraception.

• Male participants:

• Male participants are eligible to participate if they agree to thefollowing during the study intervention period and for at least 6 monthsafter the last dose of study intervention for Arms 1 to 3 and 11 Monthsafter the last dose of study intervention for Arm 4:

• 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 GSK5757810A) 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 millisecond (msec) or QTcF >480 msec forparticipants with bundle 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 millimeter of mercury (mmHg) or diastolic bloodpressure ≥ 100 mmHg during screening 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, whichever isshorter of a medicinal product prior to the first dose of study drug; or need tocontinue these drugs during the study.

• Use of strong or moderate inhibitors or inducers of CYP3A4, CYP2D6 and inhibitors orinducers of P-gp, and breast cancer resistance protein (BCRP) within 14 days priorto the first dose of study drug; or in need of continuing treatment with these drugsduring the 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.