Safety And Tolerability Of TNG462 In Patients With MTAP-deleted Solid Tumors

Study Overview

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

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.

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.

Locally Advanced Solid Tumor

DRUG: TNG462
DRUG: Pembrolizumab

TNG462-C101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2023-01-30	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-05-05
First Submitted that Met QC Criteria 2023-02-07	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-05-06
First Posted (ACTUAL) 2023-02-17	Results First Posted N/A	Last Verified 2025-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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	DRUG: TNG462 TNG462, a selective PRMT5 inhibitor, will be administered orally DRUG: Pembrolizumab An anti PD-1 antibody, will be administered intravenously
EXPERIMENTAL: Dose Expansion in NSCLC Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s)	DRUG: TNG462 TNG462, a selective PRMT5 inhibitor, will be administered orally DRUG: Pembrolizumab An anti PD-1 antibody, will be administered intravenously
EXPERIMENTAL: Dose Expansion in Mesothelioma Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s)	DRUG: TNG462 TNG462, a selective PRMT5 inhibitor, will be administered orally
EXPERIMENTAL: Dose Expansion in Pancreatic Ductal Adenocarcinoma Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s)	DRUG: TNG462 TNG462, a selective PRMT5 inhibitor, will be administered orally
EXPERIMENTAL: Dose Expansion in Sarcoma Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s)	DRUG: TNG462 TNG462, a selective PRMT5 inhibitor, will be administered orally
EXPERIMENTAL: Dose Expansion in Solid Tumors Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)	DRUG: TNG462 TNG462, a selective PRMT5 inhibitor, will be administered orally
EXPERIMENTAL: 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)	DRUG: TNG462 TNG462, a selective PRMT5 inhibitor, will be administered orally DRUG: Pembrolizumab An anti PD-1 antibody, will be administered intravenously

Primary Outcome Measures	Measure Description	Time Frame
Phase 1 Maximum Tolerated Dose	To determine the maximum tolerated dose (MTD) of TNG462 when administered as a single agent and in combination with pembrolizumab	28 days and 21 days
Phase 1 Dosing Schedule	To determine the dosing schedule of TNG462	28 days
Phase 2 Anti-neoplastic Activity	To assess anti-neoplastic activity of TNG462 administered single agent and in combination with pembrolizumab in patients with MTAP-deleted advanced solid tumors by RECIST v1.1, iRECIST or mRECIST v1.1	16 weeks and 18 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Phase 1 Anti-neoplastic Activity	To assess preliminary evidence of anti-neoplastic activity of TNG462 as a single agent and when administered in combination with pembrolizumab in patients with MTAP-deleted advanced solid tumors by RECIST v1.1, iRECIST or mRECIST v1.1	16 weeks
Phase 1 and 2 Adverse Event Profile	To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs	28 days and 21 days
Phase 1 and 2 Concentration versus Time Curve	Measure the area under the plasma concentration versus time curve (AUC)	16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration	Measure the time to achieve maximal plasma concentration (Tmax)	16 days
Phase 1 and 2 Maximum Observed Plasma Concentration	Measure the maximum observed plasma concentration (Cmax)	16 days
Phase 1 and 2 Terminal Elimination Half-life	Determine the terminal elimination half-life (t1/2)	16 days
Phase 1 and 2 Total Plasma Clearance	Determine the apparent total plasma clearance when dosed orally (CL/F)	16 days
Phase 1 and 2 Volume of Distribution	Determine the apparent volume of distribution when dosed orally (Vz/F)	16 days
Phase 1 and 2 SDMA Levels	SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462	28 days

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Tango Clinical Trials

Phone Number: (857) 320-4899

Email: clinicaltrials@tangotx.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Maeve Waldron-Lynch, MD, Tango Therapeutics, Inc.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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