Mass General - Division of Clinical Research

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

Purpose

This is a first in human study in patients with advanced or metastatic solid tumors known to have an MTAP deletion. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific MTAP-deleted tumor types. The study drug, TNG908, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 192 participants.

Condition

Locally Advanced Solid Tumor

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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

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

Study Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 6 arms (parallel)
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Dose Escalation	Participants with MTAP-deleted solid tumors will receive escalating doses of TNG908 to estimate the MTD	Drug: TNG908 TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental Dose Expansion in NSCLC	Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG908 at the identified RP2D	Drug: TNG908 TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental Dose Expansion in Mesothelioma	Participants with MTAP-deleted mesothelioma will receive TNG908 at the identified RP2D	Drug: TNG908 TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental Dose Expansion in Pancreatic Ductal Adenocarcinoma	Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG908 at the identified RP2D	Drug: TNG908 TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental Dose Expansion in Sarcoma	Participants with MTAP-deleted sarcoma (soft tissue and bone) will receive TNG908 at the identified RP2D	Drug: TNG908 TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental Dose Expansion in solid tumors	Participants with other MTAP-deleted solid tumors will receive TNG908 at the identified RP2D	Drug: TNG908 TNG908, a selective PRMT5 inhibitor, will be administered orally
Experimental Dose Expansion in Glioblastoma	Participants with MTAP-deleted relapsed/refractory glioblastoma will receive TNG908 at the identified RP2D	Drug: TNG908 TNG908, a selective PRMT5 inhibitor, will be administered orally

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status: Recruiting
Sponsor: Tango Therapeutics, Inc.

Study Contact

Tango Clinical Trials
(857) 320-4899
clinicaltrials@tangotx.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.