ClinicalTrials.gg
RecruitingNCT05732831Updated Sep 8, 2026

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

A Phase 1/2 interventional study of TNG462 and Pembrolizumab in Locally Advanced Solid Tumor, sponsored by Tango Therapeutics, Inc.. Recruiting at 26 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.

Sponsored by Tango Therapeutics, Inc. · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Started May 2023; still recruiting 3 years 5 months later.
Phase
Phase 1/2
Study type
Interventional
Enrollment
225
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Locally Advanced Solid Tumor

Keywords

  • MTAP deletion
  • PRMT5
  • cholangiocarcinoma
  • NSCLC
  • mesothelioma
  • MPNST
  • Tango
  • pancreatic
  • sarcoma
  • urothelial
  • gallbladder
  • liver
  • renal
  • breast
03

In context

Cholangiocarcinoma

824 studies on the registry are indexed under Cholangiocarcinoma; 287 are open to participants now.

This study's planned enrollment of 225 is above the median of 50 across 623 interventional studies indexed under Cholangiocarcinoma.

Browse Cholangiocarcinoma studies →

Lead sponsor

Tango Therapeutics, Inc. is the lead sponsor of 7 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Age: ≥18 years-of-age at the time of signature of the main study ICF
  2. Performance status: Performance Score of 0 to 1
  3. Confirmed histologic or cytologic diagnosis of a locally advanced, , 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 must be obtained according to local guidelines

Exclusion criteria

Exclusion Criteria:

  1. Known allergies, , or intolerance to TNG462, or its 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 agent or device
  5. Impairment of GI function or disease that may significantly alter the absorption of oral TNG462
  6. Active prior or concurrent .
  7. Central nervous system associated with progressive neurological symptoms
  8. Current active liver disease from any cause
  9. Known to be positive, unless all of the following criteria are met:

    1. ≥300/μL
    2. Undetectable viral load
    3. Receiving highly active antiretroviral therapy
  10. 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, , 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
Terms in these criteria, in plain language(11)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Excipients

The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
225 participants (estimated)

Study arms

  • 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 · Drug: Pembrolizumab

  • Experimental
    Dose Expansion in NSCLC

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

    Drug: TNG462

  • Experimental
    Dose Expansion in Mesothelioma

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

    Drug: TNG462

  • Experimental
    Dose Expansion in Pancreatic Ductal Adenocarcinoma

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

    Drug: TNG462

  • Experimental
    Dose Expansion in Sarcoma

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

    Drug: TNG462

  • Experimental
    Dose Expansion in Solid Tumors

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

    Drug: TNG462

  • 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 · Drug: Pembrolizumab

Interventions

  • DrugTNG462

    TNG462, a selective PRMT5 inhibitor, will be administered orally

  • An anti PD-1 antibody, will be administered intravenously

    Also known as: Keytruda

06

What researchers measure

Primary outcomes

  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

    Time frame: 28 days and 21 days

  2. Phase 1 Dosing Schedule

    To determine the dosing schedule of TNG462

    Time frame: 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

    Time frame: 16 weeks and 18 weeks

Secondary outcomes

  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

    Time frame: 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

    Time frame: 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)

    Time frame: 16 days

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

    Measure the time to achieve maximal plasma concentration (Tmax)

    Time frame: 16 days

  5. Phase 1 and 2 Maximum Observed Plasma Concentration

    Measure the maximum observed plasma concentration (Cmax)

    Time frame: 16 days

  6. Phase 1 and 2 Terminal Elimination Half-life

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

    Time frame: 16 days

  7. Phase 1 and 2 Total Plasma Clearance

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

    Time frame: 16 days

  8. Phase 1 and 2 Volume of Distribution

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

    Time frame: 16 days

  9. Phase 1 and 2 SDMA Levels

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

    Time frame: 28 days

07

Study locations

25 of 26 sites recruiting
  • Stanford University
    Palo Alto, California 94304, United States
    Recruiting
    • Christopher Chen · Principal investigator
  • Grand Valley Oncology
    Grand Junction, Colorado 81505, United States
    Recruiting
    • Jonathan King, MD · Principal investigator
  • Florida Cancer Specialists & Research Institute
    Lake Mary, Florida 32746, United States
    Completed

    Not enrolling at this site — choose another above.

  • Sylvester Comprehensive Cancer Center
    Miami, Florida 33136, United States
    Recruiting
    • Jose Lutzky, MD · Principal investigator
  • University Chicago Medicine
    Chicago, Illinois 60637, United States
    Recruiting
    • Hedy Kindler, MD · Principal investigator
  • Carle Cancer Center
    Urbana, Illinois 61801, United States
    Recruiting
    • Tammay Sahai, MD · Principal investigator
  • Midwestern Regional Medical Center, City of Hope Chicago
    Zion, Illinois 60099, United States
    Recruiting
    • Evan Pisick, MD · Principal investigator
  • Massachusetts General Hospital
    Boston, Massachusetts 02214, United States
    Recruiting
    • Ibiayi Dagogo-Jack, MD · Principal investigator
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
    Recruiting
    • Candace Haddox, MD · Principal investigator
  • Henry Ford Cancer Center
    Detroit, Michigan 48202, United States
    Recruiting
    • Amy Weise, DO · Principal investigator
  • New York University Langone Health
    New York, New York 10016, United States
    Recruiting
    • Salman Punekar, MD · Principal investigator
  • Sarah Cannon Tennessee Oncology
    Nashville, Tennessee 37203, United States
    Recruiting
    • David Spigel, MD · Principal investigator
  • The University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
    Recruiting
    • Jordi Rodon Ahnert, MD · Principal investigator
  • Huntsman Cancer Institute, University of Utah
    Salt Lake City, Utah 84112, United States
    Recruiting
    • Vaia Florou, MD, MS · Principal investigator
  • Next Oncology Virginia
    Fairfax, Virginia 22031, United States
    Recruiting
    • Alexander Spira, MD, PhD · Principal investigator
  • CHU de Brest
    Brest, 29200, France
    Recruiting
    • Jean-Philippe Metges, MD · Principal investigator
  • Centre Berard Leon
    Lyon, 69373, France
    Recruiting
    • Philippe Cassier, MD · Principal investigator
  • Institut de Cancerologie de l'Ouest - Hôpital Saint Herblain - PPDS
    Saint-Herblain, 44805, France
    Recruiting
    • Ludovic Doucet, MD, MSc · Principal investigator
  • Institute Gustav Roussy
    Villejuif, 94805, France
    Recruiting
    • Kaissa Ouali, MD · Principal investigator
  • Vall d'Hebron Barcelona Hospital
    Barcelona, Catalonia, Spain
    Recruiting
    • Irene Brana, MD · Principal investigator
  • Hospital HM Nou Delfos
    Barcelona, 08023, Spain
    Recruiting
    • Tatiana Hernandez Guerrero, MD · Principal investigator
  • ICO l'Hospitalet - Hospital Duran i Reynals
    Barcelona, 08908, Spain
    Recruiting
    • Mariona Calvo Campos, MD · Principal investigator
  • Hospital Universitario Fundacion Jimenez Diaz
    Madrid, 28040, Spain
    Recruiting
    • Victor Moreno Garcia, MD · Principal investigator
  • Hospital de Sanchinarro
    Madrid, 28050, Spain
    Recruiting
    • Emiliano Calvo Aller, MD · Principal investigator
  • Hospital Universitario Virgen de la Victoria
    Málaga, 29010, Spain
    Recruiting
    • Javier Garcia-Corbacho, MD · Principal investigator
  • Hospital Universitario Virgen del Rocio
    Seville, 41013, Spain
    Recruiting
    • Alejandro Falcon, MD · Principal investigator
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 8, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05732831
Lead sponsor
Tango Therapeutics, Inc.
Responsible party
Sponsor
First posted
Feb 17, 2023
Start date
May 26, 2023
Primary completion
Jun 2027 (estimated)
Completion
Jun 2028 (estimated)
Last update
Sep 8, 2026

Study contacts

Maxim Pimpkin, MD
Contact
clinicaltrials@tangotx.com
(857) 320-4899
Maxim Pimpkin, MD
study director · Tango Therapeutics, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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