Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).

The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-deleted thoracic tumors. The study also aims to determine the safety profile of Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted thoracic tumors.

Inclusion Criteria Subprotocol A, B, and C * Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years). * Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before Anvumetostat dosing. * Homozygous MTAP-deletion * Able to swallow and retain PO administered study treatment. * Disease measurable as defined by RECIST v1.1. Subprotocol A - Histologically or cytologically confirmed diagnosis of NSCLC. Arm A (Anvumetostat + carboplatin + paclitaxel + pembrolizumab): \- Predominantly squamous histology. Arm B (Anvumetostat + carboplatin + pemetrexed + pembrolizumab): \- Predominantly non-squamous histology. Arm C (Anvumetostat + pembrolizumab): \- PD-L1 positive. Subprotocol B - Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation. Subprotocol C * Histologically or cytologically confirmed diagnosis of NSCLC with brain metastases. * Brain lesion meeting RANO-BM criteria for measurable disease. Exclusion Criteria Subprotocol A, B, and C * Cardiovascular and pulmonary exclusion criteria as defined in the protocol. * Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis). * History of solid organ transplant. * Major surgery within 28 days of first dose of Anvumetostat. * Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor. * Radiation therapy within 28 days of first dose. Subprotocol A \- Autoimmune disease or immunodeficiency disease as defined in the protocol'