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

RecruitingPhase 1/2

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

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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

About the study

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.

What is being tested

Sponsor: Tango Therapeutics, Inc. · Participants: 191 · Started: Mar 24, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06810544

Locations in the U.S.

ArizonaMayo Clinic Scottsdale, Scottsdale
CaliforniaUniversity of California, Irvine, Irvine
University of California Los Angeles, Los Angeles
University of California at San Francisco, San Francisco
District of ColumbiaSibley Memorial Hospital, Washington D.C.
FloridaMayo Clinic Jacksonville, Jacksonville
IllinoisNorthwestern Memorial Hospital, Chicago
MassachusettsDana Farber Cancer Institute, Boston
MinnesotaMayo Clinic Cancer Center, Rochester
New YorkMemorial Sloan Kettering Cancer Center, New York
NYU Langone Health, New York
OhioOhio State University Comprehensive Cancer Center, Columbus
TexasMD Anderson Cancer Center, Houston
UtahUniversity of Utah, Huntsman Cancer Institute, Salt Lake City
VirginiaNEXT Virginia, Fairfax

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.