Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors

Inclusion Criteria:

1. Age: ≥18 years-of-age at the time of signature of the main study ICF

2. Performance status: ECOG Performance Score of 0 to 1

3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic,and/or unresectable solid tumor

4. Prior standard therapy, as available

5. Documented bi-allelic (homozygous) deletion of MTAP in a tumor detected by next-generation sequencing or absence of MTAP protein in a tumor detected by IHC.

6. Adequate organ function/reserve per local labs

7. Adequate liver function per local labs

8. Adequate renal function per local labs

9. Negative serum pregnancy test result at screening

10. Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

1. Known allergies, hypersensitivity, or intolerance to TNG462, or its excipients or topembrolizumab in the combination treatment arms

2. Uncontrolled intercurrent illness that will limit compliance with the studyrequirements

3. Active infection requiring systemic therapy

4. Currently participating in or has planned participation in a study of anotherinvestigational agent or device

5. Impairment of GI function or disease that may significantly alter the absorption oforal TNG462

6. Active prior or concurrent malignancy.

7. Central nervous system metastases associated with progressive neurological symptoms

8. Current active liver disease from any cause

9. Known to be HIV positive, unless all of the following criteria are met:

10. CD4+ count ≥300/μL

11. Undetectable viral load

12. Receiving highly active antiretroviral therapy

13. Clinically relevant cardiovascular disease

14. A female patient who is pregnant or lactating

15. Patient is unwilling or unable to comply with the scheduled visits, drugadministration plan, laboratory tests, biopsy, or other study procedures and studyrestrictions

16. Patient has a prior or ongoing clinically significant illness, medical condition,surgical history, physical finding, or laboratory abnormality that, in theinvestigator's opinion, may affect the safety of the patient or impair theassessment of study results