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

ClinicalTrials.gov Identifier

NCT05732831

Institution Name

The University of Texas MD Anderson Cancer Center

Full Institution Address

1515 Holcombe Blvd Houston Texas 77030 United States

Additional Institutions

Sarah Cannon Research Institute 335 24th Avenue North, Suite 200, Nashville, TN, United States, 37203 Study Contacts: PI Name: David Spigel PI Email Address: David.Spigel@SCRI.com SC Name: Brook Petrasovits SC Email Address: Brooke.Petrasovits@SCRI.com Dana Farber Cancer Institute 450 Brookline Avenue, Yakwey Building, Boston, MA, 02215 Study Contacts: PI Name: Candace Haddox PI Email Address: Candace_Haddox@DFCI.HARVARD.EDU SC Name: Kyle Beaupre SC Email Address: kyle_beaupre@dfci.harvard.edu University of Utah- Huntsman Cancer Institute 2000 Circle of Hope Drive, Salt Lake City, UT 84112 Study Contacts: PI Name: Ignacio Garrido-Laguna PI Email Address: ignacio.garrido-laguna@hci.utah.edu SC Name: Heather Bratton SC Email Address: heather.bratton@hci.utah.edu NYU Langone Health- Perlmutter Cancer Center 160 East 34th Street. New York, NY 10016 Study Contacts: PI Name: Salman Punekar PI Email Address: salman.punekar@nyulangone.org SC Name: Nicholas Hatter SC Email Address: nicholas.hatter@nyulangone.org University of Miami- Sylvester Comprehensive Cancer Center 1120 NW 14th Street, Miami, FL 33136 Study Contacts: PI Name: Jose Lutzky PI Email Address: jose.lutzky@med.miami.edu SC Name: Claudia Ramirez SC Email Address: cramirez@med.miami.edu Hospital Universitario Fundacion Jimenez Diaz Avenida Reyes Catolicos 2, Madrid, Madrid, Spain 28040 Study Contacts: PI Name: Victor Moreno Garcia PI Email Address: victor.moreno@startmadrid.com SC Name: Olga Ferrero SC Email Address: olga.ferrero@startmadrid.com Hospital Universitatio HM Sanchinarro Calle Ona 10, Madrid, Madrid, Spain, 28050 Study Contacts: PI Name: Emiliano Calvo Aller PI Email Address: emiliano.calvo@startmadrid.com SC Name: Maria Garrido SC Email Address: maria.garrido@startmadrid.com Vall d’Hebron Barcelona Hospital Passeig Vall d’Hebron, 119-129, Barcelona, Barcelona, Spain, 08035 Study Contacts: PI Name: Irene Braña Garcia PI Email Address: ibrana@vhio.net SC Name: Montse Pequera Juvany SC Email Address: montsepequera@vhio.net Centre Leon Berard 28 rue Laennec, Lyon, Cedex 08, France, 69373 Study Contacts: PI Name: Philippe Cassier PI Email Address: philippe.cassier@lyon.unicancer.fr SC Name: Anais Nuez SC Email Address: Anais.NUEZ@lyon.unicancer.fr Institute Gustav Roussy, 114, rue Edouard-Vaillant, 94805 Villejuif Cedex-France Study Contacts: PI Name: Capucine Baldini PI Email Address: capucine.baldini@gustaveroussy.fr SC Name: Ngoc Anh Le SC Email Address: ngocanh.le@gustaveroussy.fr

Principal Investigator

Jordi Rodon Ahnert

Principal Investigator Phone

(713) 792-5603

Principal Investigator Email

jrodon@mdanderson.org

Study Coordinator

Patricia Phillips

Study Coordinator Phone

(713) 745-9143

Study Coordinator Email

PEPhillips@mdanderson.org

Additional Study Coordinators

Uyen Vu umvu@mdanderson.org 713-794-1254

Study Overview

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.

Enrollment Information

Up to 159 patients

Study Start Date

20230526

Study End Date

20260531

Study Purpose

Phase 1: To determine the maximum tolerated dose and dosing schedule of TNG462 Phase 2: To assess anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1

Inclusion Criteria

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

Exclusion Criteria

Known allergies, hypersensitivity, or intolerance to TNG462 or its excipients 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: (a) CD4+ count ≥300/μL, (b) Undetectable viral load, (c) 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 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

Financial Assistance Available

Yes

---