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

September 4, 2026 updated by: Tango Therapeutics, Inc.

A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG462 as a Single Agent and in Combination in Patients With MTAP-deleted Advanced or Metastatic 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
225

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Brest, France, 29200
        • Recruiting
        • CHU de Brest
        • Principal Investigator:
          • Jean-Philippe Metges, MD
      • Lyon, France, 69373
        • Recruiting
        • Centre Berard Leon
        • Principal Investigator:
          • Philippe Cassier, MD
      • Saint-Herblain, France, 44805
        • Recruiting
        • Institut de Cancerologie de l'Ouest - Hôpital Saint Herblain - PPDS
        • Principal Investigator:
          • Ludovic Doucet, MD, MSc
      • Villejuif, France, 94805
        • Recruiting
        • Institute Gustav Roussy
        • Principal Investigator:
          • Kaissa Ouali, MD
  • Spain
      • Barcelona, Spain, 08908
        • Recruiting
        • ICO L'Hospitalet - Hospital Duran i Reynals
        • Principal Investigator:
          • Mariona Calvo Campos, MD
      • Barcelona, Spain, 08023
        • Recruiting
        • Hospital HM Nou Delfos
        • Principal Investigator:
          • Tatiana Hernandez Guerrero, MD
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundación Jiménez Díaz
        • Principal Investigator:
          • Victor Moreno Garcia, MD
      • Madrid, Spain, 28050
        • Recruiting
        • Hospital de Sanchinarro
        • Principal Investigator:
          • Emiliano Calvo Aller, MD
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Universitario Virgen de la Victoria
        • Principal Investigator:
          • Javier Garcia-Corbacho, MD
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocío
        • Principal Investigator:
          • Alejandro Falcon, MD
    • Catalonia
      • Barcelona, Catalonia, Spain
        • Recruiting
        • Vall d'Hebron Barcelona Hospital
        • Principal Investigator:
          • Irene Brana, MD
  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University
        • Principal Investigator:
          • Christopher Chen
    • Colorado
      • Grand Junction, Colorado, United States, 81505
        • Recruiting
        • Grand Valley Oncology
        • Principal Investigator:
          • Jonathan King, MD
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Completed
        • Florida Cancer Specialists & Research Institute
      • Miami, Florida, United States, 33136
        • Recruiting
        • Sylvester Comprehensive Cancer Center
        • Principal Investigator:
          • Jose Lutzky, MD
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University Chicago Medicine
        • Principal Investigator:
          • Hedy Kindler, MD
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Principal Investigator:
          • Tammay Sahai, MD
      • Zion, Illinois, United States, 60099
        • Recruiting
        • Midwestern Regional Medical Center, City of Hope Chicago
        • Principal Investigator:
          • Evan Pisick, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
        • Principal Investigator:
          • Candace Haddox, MD
      • Boston, Massachusetts, United States, 02214
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Ibiayi Dagogo-Jack, MD
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Cancer Center
        • Principal Investigator:
          • Amy Weise, DO
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • New York University Langone Health
        • Principal Investigator:
          • Salman Punekar, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Tennessee Oncology
        • Principal Investigator:
          • David Spigel, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Principal Investigator:
          • Jordi Rodon Ahnert, MD
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute, University of Utah
        • Principal Investigator:
          • Vaia Florou, MD, MS
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • NEXT Oncology Virginia
        • Principal Investigator:
          • Alexander Spira, MD, PhD

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Other Names:
  • Keytruda
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
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
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1 Dosing Schedule
Time Frame: 28 days
To determine the dosing schedule of TNG462
28 days
Phase 1 Maximum Tolerated Dose
Time Frame: 28 days and 21 days
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 2 Anti-neoplastic Activity
Time Frame: 16 weeks and 18 weeks
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1 and 2 Concentration versus Time Curve
Time Frame: 16 days
Measure the area under the plasma concentration versus time curve (AUC)
16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
Time Frame: 16 days
Measure the time to achieve maximal plasma concentration (Tmax)
16 days
Phase 1 and 2 Maximum Observed Plasma Concentration
Time Frame: 16 days
Measure the maximum observed plasma concentration (Cmax)
16 days
Phase 1 and 2 Terminal Elimination Half-life
Time Frame: 16 days
Determine the terminal elimination half-life (t1/2)
16 days
Phase 1 and 2 Total Plasma Clearance
Time Frame: 16 days
Determine the apparent total plasma clearance when dosed orally (CL/F)
16 days
Phase 1 and 2 Volume of Distribution
Time Frame: 16 days
Determine the apparent volume of distribution when dosed orally (Vz/F)
16 days
Phase 1 and 2 SDMA Levels
Time Frame: 28 days
SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462
28 days
Phase 1 Anti-neoplastic Activity
Time Frame: 16 weeks
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
Time Frame: 28 days and 21 days
To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs
28 days and 21 days

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tango Therapeutics, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Maxim Pimpkin, MD, Tango Therapeutics, Inc.

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 26, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 30, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 17, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 8, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TNG462-C101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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