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. The study is planned to treat up to 192 participants.
This is a Phase 1/2 multi-center, open label study in solid tumor patients (including glioblastoma) who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG908 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 of TNG908. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
192
TNG908, a selective PRMT5 inhibitor, will be administered orally
University of California Los Angeles
Los Angeles, California, United States
University of California San Francisco
Phase 1:
To determine the MTD and dosing schedule of TNG908
Time frame: 28 days
Phase 2:
To assess anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST or mRECIST v1.1 or modified RANO criteria
Time frame: 16 weeks
Phase 1:
To assess preliminary evidence of anti-neoplastic activity of TNG908 in patients with MTAP-deleted advanced solid tumors by RECIST or mRECIST v1.1or modified RANO criteria
Time frame: 16 weeks
Phase 1 and 2:
To describe the safety and tolerability profile of TNG908 by frequency and severity of AEs
Time frame: 28 days
Phase 1 and 2:
Area under the plasma concentration versus time curve (AUC)
Time frame: 16 days
Phase 1 and 2:
Time to achieve maximal plasma concentration (Tmax)
Time frame: 16 days
Phase 1 and 2:
Maximum observed plasma concentration (Cmax)
Time frame: 16 days
Phase 1 and 2:
Terminal elimination half-life (t1/2)
Time frame: 16 days
Phase 1 and 2:
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San Francisco, California, United States
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
Grand Valley Oncology
Grand Junction, Colorado, United States
Florida Cancer Specialists & Research Institute
Lake Mary, Florida, United States
Northwestern University
Chicago, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
...and 10 more locations
Apparent total plasma clearance when dosed orally (CL/F)
Time frame: 16 days
Phase 1 and 2:
Apparent volume of distribution when dosed orally (Vz/F)
Time frame: 16 days
Phase 1 and 2:
SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG908
Time frame: 28 days