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.
Has a tumor with a confirmed MTAP loss
Is ≥18 years of age at the time of signature of the main study ICF
Has had progression or an inadequate response to or is intolerant of the approved standard of care therapy, no standard of care therapy exists, or the investigator has determined that treatment with the standard of care therapy is not appropriate.
Is able to swallow tablets
A female patient is who is pregnant or breastfeeding
Has impaired GI function or disease that may significantly alter the absorption of oral study treatment(s)
Has an active infection requiring systemic therapy
Has received prior treatment with a PRMT5 inhibitor or a MAT2A inhibitor
Sequential
TNG456
DrugA selective PRMT5 inhibitor
abemaciclib
DrugA kinase inhibitor
7
Treatment groupsSee each treatment group below.
Phase 1 Maximum Tolerated Dose
To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib
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
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
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
Phase 1 and 2 Adverse Event Profile
To describe the safety and tolerability profile of TNG456 as a monotherapy and in combination with abemaciclib
Phase 1 and 2 Concentration versus Time Curve
Measure the area under the plasma concentration versus time curve (AUC)
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
Measure the time to achieve maximal plasma concentration (Tmax)
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Tango Therapeutics, Inc.
Lead sponsor
Eli Lilly and Company
Collaborator
