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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Safety and Tolerability of TNG456 Alone and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 - your organs (liver, kidneys, etc.) are working well enough based on blood tests/reserve per local labs - Negative serum pregnancy test result at screening - Has an ECOG performance status score of 0 to 1 - Has measurable disease based on RECIST v1.1 or a confirmed glioblastoma (IDH-wildtype) with radiographic evidence of disease progression or recurrence defined by RANO 2.0. - Has an ECOG performance score of 0 to 1 or for GBM has a Karnofsky performance status score ≥70. Who Should NOT Join This Trial: - 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 - Patients in the expansion receiving the combination therapy that have received prior treatment with a CDK4/6 inhibitor - Clinically relevant cardiovascular disease - Has a prior or ongoing clinically significant illness may affect the safety of the patient, impair the assessment of study results or compliance with the protocol Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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 * Adequate Organ function/reserve per local labs * Negative serum pregnancy test result at screening * Has an ECOG performance status score of 0 to 1 * Has measurable disease based on RECIST v1.1 or a confirmed glioblastoma (IDH-wildtype) with radiographic evidence of disease progression or recurrence defined by RANO 2.0. * Has an ECOG performance score of 0 to 1 or for GBM has a Karnofsky performance status score ≥70. Exclusion Criteria: * 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 * Patients in the expansion receiving the combination therapy that have received prior treatment with a CDK4/6 inhibitor * Clinically relevant cardiovascular disease * Has a prior or ongoing clinically significant illness may affect the safety of the patient, impair the assessment of study results or compliance with the protocol

Treatments Being Tested

DRUG

TNG456

A selective PRMT5 inhibitor

DRUG

abemaciclib

A kinase inhibitor

Locations (13)

Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
University of California, Irvine
Irvine, California, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
NYU Langone Health
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
MD Anderson Cancer Center
Houston, Texas, United States
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, United States
NEXT Virginia
Fairfax, Virginia, United States