A study to evaluate the safety, tolerability, pharmacokinetics and clinical Activity of GSK5733584 for injection in participants with advanced solid tumorsBEHOLD-1

Males or females aged 18 years or older (≥18 years).

• Participants with pathologically confirmed advanced solid tumor (who have failed or are intolerant to standard of care).
• PROC cohort a. Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer. b. Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy. c. Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy. d. Must have had prior bevacizumab if the participant was considered a candidate for this regimen and the regimen is locally available. e. Participants with known Folate receptor-α (FR-α) expressing tumors must have received mirvetuximab soravtasine if the participants was considered a candidate for this regimen and the regimen is locally available. f. Participants with known Breast cancer susceptibility gene (BRCA) mutated tumors should have received a Poly adenosine diphosphate-ribose polymerase (PARP) inhibitor if the participant was considered a candidate for this regimen and the regimen is locally available.
• Endometrial cancer cohort a) Histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer. b) Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy. c) Must have had prior platinum and PD(L)-1 inhibitor (in same regimen or in separate regimens), if considered a candidate for this regimen and the regimen is locally available. d) All epithelial histologies are permitted including carcinosarcoma.
• Participants have at least one target lesion as assessed per the RECIST 1.1
• Tumor tissue from a newly obtained biopsy or archival tumor tissue is required for retrospective detection of B7 homolog 4 (B7-H4) expression by Immunohistochemistry (IHC) in central laboratory and other biomarker analysis. Tissue from a newly obtained biopsy is preferred. If a newly obtained biopsy is not feasible, archival tumor tissue within 2 years prior to the first dose of study drug is acceptable.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2 and no deterioration within 2 weeks before the first dose.
• Have a life expectancy of at least 12 weeks.

Have received any of B7-H4-targeted therapies.

• Have received any of cytotoxic chemotherapy drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 28 days prior to the first dose of study drug; or need to continue these drugs during the study.
• Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.
• Presence of pleural/abdominal effusion/ascites requiring clinical intervention; presence of pericardial effusion
• Major surgery within 28 days prior to the first dose of study treatment.
• Evidence of brain metastasis unless asymptomatic.
• Has inadequate bone marrow reserve or hepatic/renal functions.
• Mean Fridericia-corrected QT interval (QTcF) > 470 millisecond (msec) on resting ECG.
• Evidence of current clinically significant arrhythmias or ECG abnormalities
• Risk factors of prolonged QTc or arrhythmia events,
• Left ventricular ejection fraction (LVEF) < 50%.
• Have severe, uncontrolled or active cardiovascular disorders, serious or poorly controlled hypertension, clinically significant bleeding symptoms or serious arteriovenous thromboembolic events
• Any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring high-dose systemic glucocorticoids.
• Have received prior therapy with topoisomerase inhibitors or topoisomerase inhibitor Antibody-drug conjugate (ADCs)
• PROC a. Primary platinum refractory disease defined as those who have progressed on or within 12 weeks of last dose of first line platinum therapy not permitted. b. Non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma not permitted.
• Endometrial cancer a. Mesenchymal tumors of the uterus (uterine sarcomas) not permitted.