Recruiting
Phase 1
Phase 2

TNG456 & Abemaciclib

Sponsor:

Tango Therapeutics, Inc.

Code:

NCT06810544

Conditions

Non Small Cell Lung Cancer

Glioma Glioblastoma Multiforme

Glioma, Malignant

Solid Tumor

Non-Small Cell Adenocarcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

TNG456

abemaciclib

Study Details

Brief 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.

Conditions

Non Small Cell Lung Cancer

Glioma Glioblastoma Multiforme

Glioma, Malignant

Solid Tumor

Non-Small Cell Adenocarcinoma

Study ID

NCT06810544

Start date

Mar 24, 2025

Status verified date

Apr, 2026

Completion date

Sep 30, 2027

Anticipated

Primary completion date

Mar 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

191 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Single Agent and Combination Dose Escalation

Solid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD

experimental: NSCLC Single Agent Dose Expansion

NSCLC (squamous and non squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)

experimental: GBM Single Agent Dose Expansion

GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)

experimental: Tumor Agnostic Single Agent Dose Expansion

Patients with specific solid tumor types that have a confirmed MTAP loss will receive TNG456 at the identified RP2D(s)

experimental: NSCLC Combination Expansion

NSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib

experimental: GBM Combination Expansion

GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib

experimental: Tumor Agnostic Combination Expansion

Participants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib

Interventions

TNG456

A selective PRMT5 inhibitor

abemaciclib

A kinase inhibitor

Primary outcome measure

  • Phase 1 Maximum Tolerated Dose [ Time Frame: 21 days ]
  • Phase 2 Anti-neoplastic Activity Single Agent [ Time Frame: 18 weeks ]
  • Phase 2 Anti-neoplastic Activity Combination Treatment [ Time Frame: 18 weeks ]

Central Contacts and Locations

Central contacts

Tab Cooney, MD

(857) 320-4899clinicaltrials@tangotx.com

Locations

Mayo Clinic Scottsdale

Recruiting

Scottsdale, Arizona, United States, 85259-5452

Principal Investigator:

Mitesh Borad, MD

University of California, Irvine

Recruiting

Irvine, California, United States, 92686

Principal Investigator:

Cathleen Park, MD

University of California Los Angeles

Recruiting

Los Angeles, California, United States, 90995

Principal Investigator:

Timothy Cloughesy, MD

University of California at San Francisco

Recruiting

San Francisco, California, United States, 94143-2202

Principal Investigator:

Nicolas Butowski, MD

Sibley Memorial Hospital

Recruiting

Washington D.C., District of Columbia, United States, 20016

Principal Investigator:

Solmaz Sahebjam, MD

Mayo Clinic Jacksonville

Recruiting

Jacksonville, Florida, United States, 32224

Principal Investigator:

Hani Babiker, MD

Northwestern Memorial Hospital

Recruiting

Chicago, Illinois, United States, 60611-2908

Principal Investigator:

Ditte Primdahl, MD

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Jia Luo, MD

Mayo Clinic Cancer Center

Recruiting

Rochester, Minnesota, United States, 55905-0001

Principal Investigator:

Kaushal Parikh, MD

NYU Langone Health

Recruiting

New York, New York, United States, 10016

Principal Investigator:

Salman Punekar, MD

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 11065

Principal Investigator:

Lauren Schaff, MD

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator:

Dwight Owen, MD

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Principal Investigator:

Jordi Rodon, MD

University of Utah, Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112-5500

Principal Investigator:

Howard Coleman, MD

NEXT Virginia

Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator:

Alexander Spira, MD, PhD

More Information

Sponsor

Tango Therapeutics, Inc.

Last update posted

Apr 13, 2026

Last verified

Apr, 2026

Keywords

  • MTAP
  • PRMT5 inhibitor
  • CDK 4/6
  • abemaciclib
  • Tango

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Tango Therapeutics, Inc. on 2026-04-13.