Safety and Tolerability of TNG908 in Patients With MTAP-deleted Solid Tumors

Primary Outcome Measures

1. Phase 1: [ Time Frame: 28 days ]
   To determine the MTD and dosing schedule of TNG908
2. Phase 2: [ Time Frame: 16 weeks ]
   To assess anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1

Secondary outcome Measures

1. Phase 1: [ Time Frame: 16 weeks ]
   To assess preliminary evidence of anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1
2. Phase 1 and 2: [ Time Frame: 28 days ]
   To describe the safety and tolerability profile of TNG908 by frequency and severity of AEs
3. Phase 1 and 2: [ Time Frame: 16 days ]
   Area under the plasma concentration versus time curve (AUC)
4. Phase 1 and 2: [ Time Frame: 16 days ]
   Time to achieve maximal plasma concentration (Tmax)
5. Phase 1 and 2: [ Time Frame: 16 days ]
   Maximum observed plasma concentration (Cmax)
6. Phase 1 and 2: [ Time Frame: 16 days ]
   Terminal elimination half-life (t1/2)
7. Phase 1 and 2: [ Time Frame: 16 days ]
   Apparent total plasma clearance when dosed orally (CL/F)
8. Phase 1 and 2: [ Time Frame: 16 days ]
   Apparent volume of distribution when dosed orally (Vz/F)
9. Phase 1 and 2: [ Time Frame: 28 days ]
   Assess changes in biomarker levels after dosing with TNG908

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.
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. Patient must be able to swallow tablets
11. 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. Diagnosis of malignant glioma
5. Currently participating in or has planned participation in a study of another investigational agent or device
6. Impairment of GI function or disease that may significantly alter the absorption of oral TNG908
7. Active prior or concurrent malignancy.
8. Central nervous system metastases associated with progressive neurological symptoms
9. Current active liver disease from any cause
10. 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
11. Clinically relevant cardiovascular disease
12. A female patient who is pregnant or lactating
13. Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions
14. 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