The purpose of this study is to find out if a new drug, called IDRX-42 (also known as GSK6042981), is effective in treating adults with a type of cancer called Gastrointestinal Stromal Tumors (GIST) when compared to another drug named sunitinib. The study will see if IDRX-42 works well and is safe for participants whose GIST has spread or cannot be surgically removed, and who have already taken the drug imatinib. Participants whose disease worsens after receiving sunitinib in this study may cross over to receive GSK6042981, at investigator's discretion and if additional eligibility criteria are met.

Inclusion Criteria:

• Participants with histologically or cytologically confirmed GIST that is metastatic and/or surgically unresectable.
• Documented disease progression on or intolerance to imatinib administered for first-line treatment of unresectable/metastatic disease.
• Documented mutation status of KIT and/or PDGFRA using a tissue based next-generation sequencing or polymerase chain reaction (PCR) assay.
• Tumor tissue must be available for retrospective biomarker analysis. Sample may be archival or new biopsy.

Exclusion Criteria:

• GIST that is both KIT and PDGFRA wild-type or known to harbor an activating PDGFRA exon 18 mutation.
• Known untreated or active central nervous system metastases.
• Participants with a known allergy or hypersensitivity to any component of IDRX-42 (GSK6042981) or sunitinib. Participants with a history of Stevens-Johnson syndrome on a prior Tyrosine kinase inhibitor (TKI) are excluded.
• Has a 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.

GSK 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.