The purpose of this study is to investigate a new drug GSK5533524 in adults with certain advanced cancers to find a safe dose and learn how well people tolerate it, so researchers can choose the best dose for the next stage of testing. The study will also check whether the drug can shrink tumours or slow cancer growth, monitor how the body absorbs and breaks down the drug, and look for any immune reactions that the body might develop against the treatment.

Inclusion Criteria:

• Is at least 18 years of age or the legal age of consent
• Has histologically or cytologically confirmed advanced/metastatic solid tumor that is refractory to standard therapy, for which no standard treatment is available, or who is intolerant to established standard of care therapies.
• Has documented disease progression based on radiologic imaging, during or after most recent line of treatment.
• Has at least one target lesion per RECIST 1.1 (participants in Part 1a backfill and Part 1b).
• Has an Eastern Cooperative Oncology Group performance status of 0 or 1 and no deterioration in the 2 weeks before enrollment.
• Has adequate organ function.

Exclusion Criteria:

• Has a history of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, congestive heart failure or clinically significant arrhythmia not controlled by Standard of care therapy.
• Presence of pleural/abdominal effusion/ascites requiring clinical intervention; presence of pericardial effusion.
• Has untreated brain or central nervous system metastases or metastases that have progressed
• Has a Grade ≥2 corneal epithelial condition.
• Has any active renal condition
• Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening.
• Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to ≤Grade 1 or to the baseline status preceding prior therapy.
• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or current ILD/pneumonitis.
• Has a lung-specific intercurrent clinically significant illness
• Has FEV1 <50% predicted
• Has chronic enteritis or inflammatory bowel disease or any history of clinically significant bleeding of gastrointestinal tract or clinically significant obstruction and/or perforation and/or fistulae of GI tract.
• Has a known hypersensitivity to any component of GSK5533524 or its excipients.
• Has history of severe allergies, or severe infusion related reactions, or idiosyncrasy to recombinant humanized proteins.
• Has received any cytotoxic chemotherapy drugs, or other anti-tumor drugs within 28 days prior to the first dose of study drug.
• Has 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 intervention.
• Has received immunosuppressive agents or required long-term glucocorticoid therapy within 30 days prior to first dose of study treatment.
• The use of concomitant medications known to prolong the QT/QTc interval or potentially cause torsades de pointes.
• Has corrected QT interval by Fridericia formula (QTcF) >470 msec or QTcF >480 msec for participants with bundle branch block.
• Has a left ventricular ejection fraction (LVEF) < 50%.
• Has risk factors for prolonged QT/QTc or TdP, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of any direct relative under 40 years old.

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.