AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol)

Open to people ages 18-100

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 AMG 193 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 (AMG 193 + carboplatin + paclitaxel + pembrolizumab):

• Predominantly squamous histology.

Arm B (AMG 193 + carboplatin + pemetrexed + pembrolizumab):

• Predominantly non-squamous histology.

Arm C (AMG 193 + 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.

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 AMG 193.
• Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
• Radiation therapy within 28 days of first dose.