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Locally Advanced Solid TumorPhase 1/2NCT05732831

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

A Phase 1/2 study testing TNG462 and Pembrolizumab in people with Locally Advanced Solid Tumor, run by Tango Therapeutics, Inc. at 26 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Locally Advanced Solid Tumor
What is being tested?
TNG462 and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
225 participants
Where
26 sitesin 3 countries
Study dates
26 May 2023to Jun 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: ≥18 years-of-age at the time of signature of the main study ICF
  • Performance status: ECOG Performance Score of 0 to 1
  • Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor
  • Prior standard therapy, as available
  • 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.
  • Adequate organ function/reserve per local labs
Show all 10Show fewer
  • Adequate liver function per local labs
  • Adequate renal function per local labs
  • Negative serum pregnancy test result at screening
  • Written informed consent must be obtained according to local guidelines

Who cannot join

  • Known allergies, hypersensitivity, or intolerance to TNG462, or its excipients or to pembrolizumab in the combination treatment arms
  • Uncontrolled intercurrent illness that will limit compliance with the study requirements
  • Active infection requiring systemic therapy
  • Currently participating in or has planned participation in a study of another investigational agent or device
  • Impairment of GI function or disease that may significantly alter the absorption of oral TNG462
  • Active prior or concurrent malignancy.
Show all 16Show fewer
  • Central nervous system metastases associated with progressive neurological symptoms
  • Current active liver disease from any cause
  • Known to be HIV positive, unless all of the following criteria are met:
  • CD4+ count ≥300/μL
  • Undetectable viral load
  • Receiving highly active antiretroviral therapy
  • Clinically relevant cardiovascular disease
  • A female patient who is pregnant or lactating
  • Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions
  • 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

Trial locations and contacts

26 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Maxim Pimpkin, MD contact

(857) 320-4899

clinicaltrials@tangotx.com

26 sites in 3 countries

United States15 sites, 14 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

    Ibiayi Dagogo-Jack, MD

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Candace Haddox, MD

    Recruiting

  • University Chicago Medicine

    Chicago, Illinois, 60637

    Hedy Kindler, MD

    Recruiting

  • Henry Ford Cancer Center

    Detroit, Michigan, 48202

    Amy Weise, DO

    Recruiting

  • Next Oncology Virginia

    Fairfax, Virginia, 22031

    Alexander Spira, MD, PhD

    Recruiting

  • Grand Valley Oncology

    Grand Junction, Colorado, 81505

    Jonathan King, MD

    Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Jordi Rodon Ahnert, MD

    Recruiting

  • Florida Cancer Specialists & Research Institute

    Lake Mary, Florida, 32746

    Completed

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

    Jose Lutzky, MD

    Recruiting

  • Sarah Cannon Tennessee Oncology

    Nashville, Tennessee, 37203

    David Spigel, MD

    Recruiting

  • New York University Langone Health

    New York, New York, 10016

    Salman Punekar, MD

    Recruiting

  • Stanford University

    Palo Alto, California, 94304

    Christopher Chen

    Recruiting

  • Huntsman Cancer Institute, University of Utah

    Salt Lake City, Utah, 84112

    Vaia Florou, MD, MS

    Recruiting

  • Carle Cancer Center

    Urbana, Illinois, 61801

    Tammay Sahai, MD

    Recruiting

  • Midwestern Regional Medical Center, City of Hope Chicago

    Zion, Illinois, 60099

    Evan Pisick, MD

    Recruiting

Other trials in United States

Spain7 sites, 7 recruiting

  • Vall d'Hebron Barcelona Hospital

    Barcelona, Catalonia

    Irene Brana, MD

    Recruiting

  • Hospital HM Nou Delfos

    Barcelona, 08023

    Tatiana Hernandez Guerrero, MD

    Recruiting

  • ICO l'Hospitalet - Hospital Duran i Reynals

    Barcelona, 08908

    Mariona Calvo Campos, MD

    Recruiting

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040

    Victor Moreno Garcia, MD

    Recruiting

  • Hospital de Sanchinarro

    Madrid, 28050

    Emiliano Calvo Aller, MD

    Recruiting

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

    Javier Garcia-Corbacho, MD

    Recruiting

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

    Alejandro Falcon, MD

    Recruiting

Other trials in Spain

France4 sites, 4 recruiting

  • CHU de Brest

    Brest, 29200

    Jean-Philippe Metges, MD

    Recruiting

  • Centre Berard Leon

    Lyon, 69373

    Philippe Cassier, MD

    Recruiting

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

    Saint-Herblain, 44805

    Ludovic Doucet, MD, MSc

    Recruiting

  • Institute Gustav Roussy

    Villejuif, 94805

    Kaissa Ouali, MD

    Recruiting

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
TNG462, Pembrolizumab
Keywords
MTAP deletion, PRMT5, cholangiocarcinoma, NSCLC, mesothelioma, MPNST, Tango, pancreatic, sarcoma, urothelial, gallbladder, liver, renal, breast
Medical subject headings
Cholangiocarcinoma, Mesothelioma, Neurofibrosarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TNG462Drug

    TNG462, a selective PRMT5 inhibitor, will be administered orally

  • PembrolizumabDrug

    Also called Keytruda

    An anti PD-1 antibody, will be administered intravenously

Study groups in NCT05732831
Study groupRoleWhat they receive
Dose EscalationExperimentalParticipants 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
Receives: Drug: TNG462; Drug: Pembrolizumab
Dose Expansion in NSCLCExperimentalParticipants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s)
Receives: Drug: TNG462
Dose Expansion in MesotheliomaExperimentalParticipants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s)
Receives: Drug: TNG462
Dose Expansion in Pancreatic Ductal AdenocarcinomaExperimentalParticipants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s)
Receives: Drug: TNG462
Dose Expansion in SarcomaExperimentalParticipants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s)
Receives: Drug: TNG462
Dose Expansion in Solid TumorsExperimentalParticipants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)
Receives: Drug: TNG462
Dose Expansion in NSCLC in Combination with PembrolizumabExperimentalParticipants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)
Receives: Drug: TNG462; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 28 days and 21 days

  2. Phase 1 Dosing Schedule

    To determine the dosing schedule of TNG462

    Measured: 28 days

  3. 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

    Measured: 16 weeks and 18 weeks

Secondary outcomes (9)

  1. 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

    Measured: 16 weeks

  2. Phase 1 and 2 Adverse Event Profile

    To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs

    Measured: 28 days and 21 days

  3. Phase 1 and 2 Concentration versus Time Curve

    Measure the area under the plasma concentration versus time curve (AUC)

    Measured: 16 days

  4. Phase 1 and 2 Time to Achieve Maximal Plasma Concentration

    Measure the time to achieve maximal plasma concentration (Tmax)

    Measured: 16 days

  5. Phase 1 and 2 Maximum Observed Plasma Concentration

    Measure the maximum observed plasma concentration (Cmax)

    Measured: 16 days

  6. Phase 1 and 2 Terminal Elimination Half-life

    Determine the terminal elimination half-life (t1/2)

    Measured: 16 days

  7. Phase 1 and 2 Total Plasma Clearance

    Determine the apparent total plasma clearance when dosed orally (CL/F)

    Measured: 16 days

  8. Phase 1 and 2 Volume of Distribution

    Determine the apparent volume of distribution when dosed orally (Vz/F)

    Measured: 16 days

  9. Phase 1 and 2 SDMA Levels

    SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2023
  2. Study start26 May 2023
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 5 arms (parallel)
Masking
None (open label)
Enrolment
225 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05732831
Sponsor's protocol ID
TNG462-C101
Status last verified
Sep 2026
First submitted
30 Jan 2023
Last updated
8 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TNG462 and Pembrolizumab in people with Locally Advanced Solid Tumor, run by Tango Therapeutics, Inc. at 26 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Spain, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Maxim Pimpkin, MD ((857) 320-4899, clinicaltrials@tangotx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1 Maximum Tolerated Dose (time frame: 28 days and 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05732831.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.

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