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• Participants must be 18 years of age inclusive or older, at the time of signing the informed consent, or the legal age of consent in the jurisdiction in which the study is taking place.
• Participant capable of giving signed informed consent including compliance with the requirements and restrictions listed in the Informed consent form (ICF) and in this protocol.
• Participants with pathologically confirmed advanced solid tumor specific for study arms (key local diagnostic molecular and/or immunophenotyping testing results/tumor cell phenotype results for confirmed diagnosis should be provided) who have failed in adequate standard treatments, do not have effective standard treatment or are intolerant to standard of care, with no more than 4 lines of prior systemic therapies.
• Requirements for tumor tissue samples: Archival or fresh tumor tissue is required for retrospective central assessment of B7H4 expression by IHC and other biomarker analysis. The archival tumor tissue should be from the most recent procedure (ideally obtained after the last anti-cancer treatment). If an archival tissue is not available a new biopsy should be performed, and the newly obtained tissue provided.
• Participants have at least one target lesion as assessed per the RECIST 1.1. A target lesion is defined as a measurable lesion that has not undergone locoregional treatment such as irradiation or that has unequivocal progression following locoregional treatment, with the longest diameter of ≥ 10 mm at baseline (for lymph node 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 following during the study intervention period and for at least 6 months after the last dose 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 that is highly effective

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

  • Has an ECOG performance status of 0 to 1.
  • Participants with normal organ and bone marrow function

• Has a second 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 metastatic disease.
• Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
• Has known sensitivity to study intervention components, GSK5733584 (antibody-drug conjugate, antibody, free cytotoxin GSK5757810) and combination partner, or its excipients 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 cardiac disease, acute myocardial infarction, or clinically significant arrhythmia not controlled by standard of care therapy.
  2. Corrected QT Interval (QTcF) >450 msec or QTcF >480 msec for participants with bundle branch block
• Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis.
• Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary).
• Clinically significant bleeding symptoms, significant bleeding tendency, or bleeding tumors 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 poor blood pressure control within 2 weeks prior to the first dose of study treatment; systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg during screening period.
• Has any active renal condition (e.g., infection, requirement for dialysis, or any other active significant renal condition or dehydrated condition that could affect the 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 for participants 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-tumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy, biotherapy, and investigational drug) within 30 days or 5 half-lives of a medicinal product prior to the first dose of study drug; or need to continue these drugs during the study.
• Use strong inhibitors or inducers of CYP3A4, CYP2D6, P-gp, or breast cancer resistance protein (BCRP) with narrow therapeutic window within 14 days prior to the first dose of study drug; or in need of continuing treatment with 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.