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

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'