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

Prior treatment

• Major surgery within 28 days of first dose of Anvumetostat.
• Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.

Other illness

• 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.
• Radiation therapy within 28 days of first dose.
  • Subprotocol A
  • \- Autoimmune disease or immunodeficiency disease as defined in the protocol'

Other

• Subprotocol A, B, and C
• Cardiovascular and pulmonary exclusion criteria as defined in the protocol.

• 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.