Study on AMG 193 and IDE397 for Advanced MTAP-Null Solid Tumors

Inclusion Criteria

1. Evidence of homozygous loss of MTAP (null) and/or MTAP deletion.

2. Presence of advanced/metastatic solid tumor not amenable to curative treatment

   1. Part 1: MTAP-null or lost MTAP expression solid tumor for which no standard therapy exists
   2. Part 2: MTAP-null or lost MTAP expression NSCLC with progression after 1 to 2 prior lines of systemic therapy.

3. Able to swallow and retain PO administered study treatment and willing to record adherence to investigational product

4. Disease measurable as defined by RECIST v1.1

5. Adequate organ function as defined in the protocol.

6. Archived tumor tissue. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before cycle 1 day 1 dosing.

Exclusion Criteria

1. Prior treatment with an MAT2A inhibitor or a PRMT5 inhibitor.
2. Radiologic or clinical evidence of spinal cord compression, untreated or symptomatic brain metastases or leptomeningeal disease.
3. Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
4. 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)
5. History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study entry.
6. Prior irradiation to > 25% of the bone marrow
7. Use of prescription medications that are known strong CYP3A4/5 inducers or strong CYP3A4/5 inhibitors within 7 days for CYP3A4/5 inhibitors, 14 days for CYP3A4/5 inducers or 5 half-lives, whichever is longer, prior to any dose of investigational medical product.