Clinical Trial Finder

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 or Karnofsky performance status score ≥70. 3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor or for GBM, have R/R disease. 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 TNG908 or its excipients. 2. Uncontrolled intercurrent illness that will limit compliance with the study requirements. 3. Active infection requiring systemic therapy. 4. Currently participating in or has planned participation in a study of another investigational agent or device. 5. Impairment of GI function or disease that may significantly alter the absorption of oral TNG908. 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: 1. CD4+ count ≥300/μL. 2. Undetectable viral load. 3. Receiving highly active antiretroviral therapy. 10. Clinically relevant cardiovascular disease. 11. A female patient who is pregnant or lactating. 12. Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions. 13. Patient has a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, may affect the safety of the patient or impair the assessment of study results

This is a Phase 1/2 multi-center, open label study in solid tumor patients (including glioblastoma) who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG908 in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 6 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D of TNG908. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

Arms

Experimental: Dose Escalation

Participants with MTAP-deleted solid tumors will receive escalating doses of TNG908 to estimate the MTD

Experimental: Dose Expansion in NSCLC

Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG908 at the identified RP2D

Experimental: Dose Expansion in Mesothelioma

Participants with MTAP-deleted mesothelioma will receive TNG908 at the identified RP2D

Experimental: Dose Expansion in Pancreatic Ductal Adenocarcinoma

Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG908 at the identified RP2D

Experimental: Dose Expansion in Sarcoma

Participants with MTAP-deleted sarcoma (soft tissue and bone) will receive TNG908 at the identified RP2D

Experimental: Dose Expansion in solid tumors

Participants with other MTAP-deleted solid tumors will receive TNG908 at the identified RP2D

Experimental: Dose Expansion in Glioblastoma

Participants with MTAP-deleted relapsed/refractory glioblastoma will receive TNG908 at the identified RP2D

Interventions

Drug: - TNG908

TNG908, a selective PRMT5 inhibitor, will be administered orally