Safety and Tolerability of TNG908 in Patients with MTAP-deleted Solid Tumors

Study Name
	Safety and Tolerability of TNG908 in Patients with MTAP-deleted Solid Tumors
ClinicalTrials.gov Identifier (if applicable)
	NCT05275478
Clinical Trial Category (check all that apply)
	Beyond First Line Therapy Targeted Therapy
Study Center
Institution Name
	NEXT Oncology
Institution Address
	2829 Babcock Road
City
	San Antonio
State
	Texas
Zip Code
	78229
Country
	United States
List additional Principal Investigators (include phone number and email)
	Alex Spira aspira@nextoncology.com
Study Coordinator
	Cynthia De Leon
Study Coordinator Email
	cdeleon@nextoncology.com
List additional Study Coordinators (include phone number and email)
	Carrie Friedman carrie.friedman@usoncology.com
Location #1
	The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, United States 77030
Location #1 Study Contacts
	Principal Investigator Name: Jordi Rodon Ahnert Principal Investigator Email Address: jrodon@mdanderson.org Principal Investigator Phone: 713-792-5603 Study Coordinator Name: Uyen Vu Study Coordinator Phone: 713-794-1254 Study Coordinator Email Address: umvu@mdanderson.org
Location #2
	Sarah Cannon Research Institute – Tennessee Oncology, Institution Address: 250 25th Avenue, Suite 307, Nashville, TN, United States, 37203
Location #2 Study Contacts
	Principal Investigator Name: David Spigel Principal Investigator Email Address: David.Spigel@sarahcannon.com Study Coordinator Name: Brook Petrasovits Study Coordinator Email Address: Brooke.Petrasovits@sarahcannon.com
Location #3
	Institution Name: Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02144
Location #3 Study Contacts
	Principal Investigator Name: Ibiayi Dagogo-Jack Principal Investigator Email Address: idagogo-jack@partners.org Study Coordinator Name: Shawna Wolfson Study Coordinator Email Address: swolfson@mgh.harvard.edu
Location #4
	Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8076, St. Louis, MO 63110
Location #4 Study Contacts
	PI Name: Angela Hirbe PI Email Address: hirbea@wustl.edu SC Name: Ena Zukanovic SC Email Address: ena@wustl.edu
Location #5
	Centre Leon Berard, 28 rue Laennec, Lyon, Cedex 08, France, 69373
Location #5 Study Contacts
	PI Name: Philippe Cassier PI Email Address: philippe.cassier@lyon.unicancer.fr SC Name: Marie Warren Lepercq SC Email Address: Mariewarren.lepercq@lyon.unicancer.fr
Location #6
	Institute Gustav Roussy, 114, rue Edouard-Vaillant, 94805 Villejuif Cedex-France
Location #6 Study Contacts
	PI Name: Capucine Baldini PI Email Address: capucine.baldini@gustaveroussy.fr SC Name: Naima Dziri-Chikdene SC Email Address: naima.dziri-chikdene@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, TNG908, is a selective PRMT5 inhibitor administered orally.
Enrollment
	Up to 192 patients.
Study Start Date
	03/23/2022
Estimated Completion Date
	04/30/2025
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 TNG908 Phase 2: To assess anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1 or modified RANO.
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 live 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 TNG908 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 stud of another investigational agent or device Impairment of GI function or disease that may significantly alter the absorption of oral TNG908 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 investigators opinion, may affect the safety of the patient or impair the assessment of study results