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 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) 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 is considered a separate line of therapy. If an agent in a regimen is switched to another agent in the same class due to toxicity or intolerance (e.g. hypersensitivity reaction) this is considered part of the same line (i.e. not counted independently).
• •Requirements for tumor tissue samples: Archival or fresh tumor tissue is required for retrospective central assessment of B7H4 expression by immunohistochemistry (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 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 millimeter (mm) at Baseline (for lymph node lesions, the short axis should be ≥ 15 mm).
• •Participants have a life expectancy of at least 12 weeks per investigator assessment based on disease burden and extent of supportive care needed.
• •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.
• •1. Diagnosis of endometrial cancer with confirmed mismatch repair proficient (MMRp) or microsatellites stable (MSS) tumor status by local test.
• •2. Participants who have progressed on or are intolerant to at least 1 line of standard prior systemic therapy (including neoadjuvant or adjuvant as prior line), and who are not candidates for curative external radiotherapy or brachytherapy. Maintenance therapy will be considered part of the preceding line of therapy (i.e, not counted independently).
• •3. Participants naïve to anti-programmed death protein 1 and/or programmed death ligand 1 (PD\[L\]-1) anti-cancer therapy.
• •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.
• •1. Participants whose advanced ovarian cancer/fallopian tube/peritoneal cancer has relapsed 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 standard prior 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 the following during the study intervention period and for at least 6 months after the last dose of study intervention for Arms 1 to 3 and 11 Months after 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 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