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.
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
- Type of treatment
- Pill or oral medicine, Injection or infusion
- 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
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.
26 sites in 3 countries
United States15 sites, 14 recruiting
- 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
- Completed
Florida Cancer Specialists & Research Institute
Lake Mary, Florida, 32746
- Recruiting
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
Spain7 sites, 7 recruiting
- 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
France4 sites, 4 recruiting
- 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
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.
- Conditions
- Locally Advanced Solid Tumor
- 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 group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | 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 Receives: Drug: TNG462; Drug: Pembrolizumab |
| Dose Expansion in NSCLC | Experimental | Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s) Receives: Drug: TNG462 |
| Dose Expansion in Mesothelioma | Experimental | Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s) Receives: Drug: TNG462 |
| Dose Expansion in Pancreatic Ductal Adenocarcinoma | Experimental | Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s) Receives: Drug: TNG462 |
| Dose Expansion in Sarcoma | Experimental | Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s) Receives: Drug: TNG462 |
| Dose Expansion in Solid Tumors | Experimental | Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s) Receives: Drug: TNG462 |
| Dose Expansion in NSCLC in Combination with Pembrolizumab | Experimental | Participants 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.
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
Phase 1 Dosing Schedule
To determine the dosing schedule of TNG462
Measured: 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
Measured: 16 weeks and 18 weeks
Secondary outcomes (9)
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
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
Phase 1 and 2 Concentration versus Time Curve
Measure the area under the plasma concentration versus time curve (AUC)
Measured: 16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
Measure the time to achieve maximal plasma concentration (Tmax)
Measured: 16 days
Phase 1 and 2 Maximum Observed Plasma Concentration
Measure the maximum observed plasma concentration (Cmax)
Measured: 16 days
Phase 1 and 2 Terminal Elimination Half-life
Determine the terminal elimination half-life (t1/2)
Measured: 16 days
Phase 1 and 2 Total Plasma Clearance
Determine the apparent total plasma clearance when dosed orally (CL/F)
Measured: 16 days
Phase 1 and 2 Volume of Distribution
Determine the apparent volume of distribution when dosed orally (Vz/F)
Measured: 16 days
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.
- First posted17 Feb 2023
- Study start26 May 2023
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Tango Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Maxim Pimpkin, MD, Study director, Tango Therapeutics, Inc.
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