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

NCT ID: NCT05275478

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

192 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-23

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Locally Advanced Solid Tumor

Keywords

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MTAP deletion PRMT5 cholangiocarcinoma NSCLC mesothelioma MPNST Tango Glioblastoma multiforme pancreatic GBM sarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 6 arms (parallel)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation

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

Group Type EXPERIMENTAL

TNG908

Intervention Type DRUG

TNG908, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in NSCLC

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

Group Type EXPERIMENTAL

TNG908

Intervention Type DRUG

TNG908, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Mesothelioma

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

Group Type EXPERIMENTAL

TNG908

Intervention Type DRUG

TNG908, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Pancreatic Ductal Adenocarcinoma

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

Group Type EXPERIMENTAL

TNG908

Intervention Type DRUG

TNG908, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Sarcoma

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

Group Type EXPERIMENTAL

TNG908

Intervention Type DRUG

TNG908, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in solid tumors

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

Group Type EXPERIMENTAL

TNG908

Intervention Type DRUG

TNG908, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Glioblastoma

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

Group Type EXPERIMENTAL

TNG908

Intervention Type DRUG

TNG908, a selective PRMT5 inhibitor, will be administered orally

Interventions

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TNG908

TNG908, a selective PRMT5 inhibitor, will be administered orally

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tango Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maxim Pimkin, MD, PhD

Role: STUDY_DIRECTOR

Tango Therapeutics, Inc.

Locations

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University of California Los Angeles

Los Angeles, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Site Status

Grand Valley Oncology

Grand Junction, Colorado, United States

Site Status

Florida Cancer Specialists & Research Institute

Lake Mary, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

NYU Langone Health

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Sarah Cannon Tennessee Oncology

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

NEXT Oncology

Fairfax, Virginia, United States

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

EDOG Institut de Cancerologie de l'Ouest

Saint-Herblain, , France

Site Status

Institut Oncopole Claudius Regaud

Toulouse, , France

Site Status

Institute Gustav Roussy

Villejuif, , France

Site Status

Countries

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United States France

References

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Briggs KJ, Cottrell KM, Tonini MR, Tsai A, Zhang M, Whittington DA, Zhang W, Lombardo SA, Yoda S, Wilker EW, Meier SR, Yu Y, Teng T, Huang A, Maxwell JP. TNG908 is a brain-penetrant, MTA-cooperative PRMT5 inhibitor developed for the treatment of MTAP-deleted cancers. Transl Oncol. 2025 Feb;52:102264. doi: 10.1016/j.tranon.2024.102264. Epub 2025 Jan 4.

Reference Type DERIVED
PMID: 39756156 (View on PubMed)

Other Identifiers

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TNG908-C101

Identifier Type: -

Identifier Source: org_study_id