Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors
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
1 other identifier
interventional
225
3 countries
26
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2023
Typical duration for phase_1
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 30, 2023
CompletedFirst Posted
Study publicly available on registry
February 17, 2023
CompletedStudy Start
First participant enrolled
May 26, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2026
ExpectedApril 21, 2026
April 1, 2026
2.9 years
January 30, 2023
April 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 Outcomes (9)
Phase 1 Anti-neoplastic Activity
16 weeks
Phase 1 and 2 Adverse Event Profile
28 days and 21 days
Phase 1 and 2 Concentration versus Time Curve
16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
16 days
Phase 1 and 2 Maximum Observed Plasma Concentration
16 days
- +4 more secondary outcomes
Study Arms (7)
Dose Escalation
EXPERIMENTALParticipants 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
Dose Expansion in NSCLC
EXPERIMENTALParticipants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s)
Dose Expansion in Mesothelioma
EXPERIMENTALParticipants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s)
Dose Expansion in Pancreatic Ductal Adenocarcinoma
EXPERIMENTALParticipants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s)
Dose Expansion in Sarcoma
EXPERIMENTALParticipants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s)
Dose Expansion in Solid Tumors
EXPERIMENTALParticipants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)
Dose Expansion in NSCLC in Combination with Pembrolizumab
EXPERIMENTALParticipants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)
Interventions
TNG462, a selective PRMT5 inhibitor, will be administered orally
An anti PD-1 antibody, will be administered intravenously
Eligibility Criteria
You may qualify if:
- 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
- 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
You may not qualify if:
- 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.
- 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
Stanford University
Palo Alto, California, 94304, United States
Grand Valley Oncology
Grand Junction, Colorado, 81505, United States
Florida Cancer Specialists & Research Institute
Lake Mary, Florida, 32746, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
University Chicago Medicine
Chicago, Illinois, 60637, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Midwestern Regional Medical Center, City of Hope Chicago
Zion, Illinois, 60099, United States
Massachusetts General Hospital
Boston, Massachusetts, 02214, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Henry Ford Cancer Center
Detroit, Michigan, 48202, United States
New York University Langone Health
New York, New York, 10016, United States
Sarah Cannon Tennessee Oncology
Nashville, Tennessee, 37203, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112, United States
Next Oncology Virginia
Fairfax, Virginia, 22031, United States
CHU de Brest
Brest, 29200, France
Centre Berard Leon
Lyon, 69373, France
Institut de Cancerologie de l'Ouest - Hôpital Saint Herblain - PPDS
Saint-Herblain, 44805, France
Institute Gustav Roussy
Villejuif, 94805, France
Vall d'Hebron Barcelona Hospital
Barcelona, Catalonia, Spain
Hospital HM Nou Delfos
Barcelona, 08023, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona, 08908, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040, Spain
Hospital de Sanchinarro
Madrid, 28050, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Universitario Virgen del Rocio
Seville, 41013, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Maxim Pimpkin, MD
Tango Therapeutics, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 30, 2023
First Posted
February 17, 2023
Study Start
May 26, 2023
Primary Completion
May 1, 2026
Study Completion (Estimated)
September 1, 2026
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share