Safety and Tolerability of TNG456 Alone 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.

Interventions

• TNG456 · DRUG

  A selective PRMT5 inhibitor

• abemaciclib · DRUG

  A kinase inhibitor

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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

Sites (15)

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