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

NCT ID: NCT05732831

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

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-26

Study Completion Date

2026-09-30

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, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 225 participants.

Detailed Description

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This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG462 administered as a single agent and in combination with pembrolizumab 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(s) of TNG462 and in combination. 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 pancreatic sarcoma urothelial gallbladder liver renal breast

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 5 arms (parallel)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation

Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 single agent and in combination with pembrolizumab to estimate the MTD

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

TNG462, a selective PRMT5 inhibitor, will be administered orally

Pembrolizumab

Intervention Type DRUG

An anti PD-1 antibody, will be administered intravenously

Dose Expansion in NSCLC

Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s)

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

TNG462, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Mesothelioma

Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s)

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

TNG462, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Pancreatic Ductal Adenocarcinoma

Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s)

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

TNG462, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Sarcoma

Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s)

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

TNG462, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in Solid Tumors

Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

TNG462, a selective PRMT5 inhibitor, will be administered orally

Dose Expansion in NSCLC in Combination with Pembrolizumab

Participants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)

Group Type EXPERIMENTAL

TNG462

Intervention Type DRUG

TNG462, a selective PRMT5 inhibitor, will be administered orally

Pembrolizumab

Intervention Type DRUG

An anti PD-1 antibody, will be administered intravenously

Interventions

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TNG462

TNG462, a selective PRMT5 inhibitor, will be administered orally

Intervention Type DRUG

Pembrolizumab

An anti PD-1 antibody, will be administered intravenously

Intervention Type DRUG

Other Intervention Names

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Keytruda

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
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 to pembrolizumab in the combination treatment arms
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 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:

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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Maeve Waldron-Lynch, MD

Role: STUDY_DIRECTOR

Tango Therapeutics, Inc.

Locations

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Stanford University

Palo Alto, California, United States

Site Status RECRUITING

Grand Valley Oncology

Grand Junction, Colorado, United States

Site Status RECRUITING

Florida Cancer Specialists & Research Institute

Lake Mary, Florida, United States

Site Status RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status RECRUITING

University Chicago Medicine

Chicago, Illinois, United States

Site Status RECRUITING

Carle Cancer Center

Urbana, Illinois, United States

Site Status RECRUITING

Midwestern Regional Medical Center, City of Hope Chicago

Zion, Illinois, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Henry Ford Cancer Center

Detroit, Michigan, United States

Site Status RECRUITING

New York University Langone Health

New York, New York, United States

Site Status RECRUITING

Sarah Cannon Tennessee Oncology

Nashville, Tennessee, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Next Oncology Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

CHU de Brest

Brest, , France

Site Status RECRUITING

Centre Berard Leon

Lyon, , France

Site Status RECRUITING

Institut de Cancerologie de l'Ouest - Hôpital Saint Herblain - PPDS

Saint-Herblain, , France

Site Status RECRUITING

Institute Gustav Roussy

Villejuif, , France

Site Status RECRUITING

Vall d'Hebron Barcelona Hospital

Barcelona, Catalonia, Spain

Site Status RECRUITING

Hospital HM Nou Delfos

Barcelona, , Spain

Site Status RECRUITING

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status RECRUITING

Hospital de Sanchinarro

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status RECRUITING

Countries

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United States France Spain

Central Contacts

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Tango Clinical Trials

Role: CONTACT

Phone: (857) 320-4899

Email: [email protected]

Other Identifiers

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TNG462-C101

Identifier Type: -

Identifier Source: org_study_id