A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG456 Monotherapy and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss
Summary
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.
Detailed description
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.
Arms & interventions
- DrugTNG456
A selective PRMT5 inhibitor
- Drugabemaciclib
A kinase inhibitor
Outcome measures
Primary
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
Secondary
Phase 1 Anti-neoplastic Activity Single Agent
Time frame: 18 weeks
Phase 1 and 2 Adverse Event Profile
Time frame: 21 days
Phase 1 and 2 Concentration versus Time Curve
Time frame: 16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
Time frame: 16 days
Phase 1 and 2 Maximum Observed Plasma Concentration
Time frame: 16 days
Eligibility criteria
Study locations (15)
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5452
University of California, Irvine
Irvine, California, 92686
University of California Los Angeles
Los Angeles, California, 90995
University of California at San Francisco
San Francisco, California, 94143-2202
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Northwestern Memorial Hospital
Chicago, Illinois, 60611-2908
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905-0001
NYU Langone Health
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 11065
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
MD Anderson Cancer Center
Houston, Texas, 77030
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112-5500
NEXT Virginia
Fairfax, Virginia, 22031