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

Study Name
	Safety and Tolerability of TNG462 in Patients with MTAP-deleted Solid Tumors
ClinicalTrials.gov Identifier (if applicable)
	NCT05732831
Clinical Trial Category (check all that apply)
	Beyond First Line Therapy Targeted Therapy
Study Center
Institution Name
	The University of Texas MD Anderson Cancer Center
Institution Address
	1515 Holcombe Blvd
City
	Houston
State
	Texas
Zip Code
	77030
Country
	United States
Study Contacts
Principal Investigator
	Jordi Rodon Ahnert
P.I. Phone
	(713) 792-5603
P.I. Email
	jrodon@mdanderson.org
Study Coordinator
	Patricia Phillips
Study Coordinator Phone
	(713) 745-9143
Study Coordinator Email
	PEPhillips@mdanderson.org
List additional Study Coordinators (include phone number and email)
	Uyen Vu umvu@mdanderson.org 713-794-1254
Additional Locations
	Sarah Cannon Research Institute 250 25th Avenue, Suite 307, Nashville, TN, United States, 37203 Study Contacts: PI Name: David Spigel PI Email Address: David.Spigel@sarahcannon.com SC Name: Brook Petrasovits SC Email Address: Brooke.Petrasovits@sarahcannon.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
OVERVIEW – in layman’s terms (150 words max)
	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
	Up to 159 patients
Study Start Date
	05/26/2023
Estimated Completion Date
	05/31/2026
Purpose of the Study – in Layman’s Terms (use the “+” to add more list items)
	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 – Patients Must:
	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 – Patients Must NOT:
	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 is available to participants for travel, lodging, etc.
	Yes