This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors known to have an MTAP loss. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific solid tumor types with a confirmed MTAP loss. The study drug, TNG456, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 191 participants.
This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed MTAP loss in their tumor. The Phase 1 portion is a dose escalation study of oral TNG456 administered as a single agent and in combination with oral abemaciclib in solid tumor patients with confirmed MTAP loss. In the Phase 2 expansion part of the study, 6 arms defined by confirmed tumor types will enroll in parallel at the RP2D(s) of TNG456 and in combination. 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
191
A selective PRMT5 inhibitor
A kinase inhibitor
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
RECRUITINGUniversity of California, Irvine
Irvine, California, United States
RECRUITINGSibley Memorial Hospital
Washington D.C., District of Columbia, United States
RECRUITINGMayo Clinic Jacksonville
Jacksonville, Florida, United States
RECRUITINGNorthwestern Memorial Hospital
Chicago, Illinois, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGMayo Clinic Cancer Center
Rochester, Minnesota, United States
RECRUITINGNYU Langone Health
New York, New York, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGOhio State University Comprehensive Cancer Center
Columbus, Ohio, United States
RECRUITING...and 3 more locations
Phase 1 Maximum Tolerated Dose
To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib
Time frame: 21 days
Phase 2 Anti-neoplastic Activity Single Agent
To assess the antitumor activity of TNG456 in patients with advanced or metastatic solid tumors with MTAP loss by RECIST or modified RANO criteria
Time frame: 18 weeks
Phase 2 Anti-neoplastic Activity Combination Treatment
To assess the antitumor activity of TNG456 in combination with abemaciclib in patients with advanced or metastatic tumors with MTAP loss by RECIST or modified RANO criteria
Time frame: 18 weeks
Phase 1 Anti-neoplastic Activity Single Agent
To assess preliminary evidence of antitumor activity of TNG456 in patients with advanced solid tumors with MTAP loss by RECIST or modified RANO criteria
Time frame: 18 weeks
Phase 1 and 2 Adverse Event Profile
To describe the safety and tolerability profile of TNG456 as a monotherapy and in combination with abemaciclib
Time frame: 21 days
Phase 1 and 2 Concentration versus Time Curve
Measure the area under the plasma concentration versus time curve (AUC)
Time frame: 16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
Measure the time to achieve maximal plasma concentration (Tmax)
Time frame: 16 days
Phase 1 and 2 Maximum Observed Plasma Concentration
Measure the maximum observed plasma concentration (Cmax)
Time frame: 16 days
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