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RecruitingInterventionalPhase 1/Phase 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

NCT ID: NCT06810544Sponsor: Tango Therapeutics, Inc.Last updated: 2026-04-13

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.

Detailed description

This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed MTAP loss in their tumor. The Phase 1 portion is a dose escalation study of oral TNG456 administered as a single agent and in combination with oral abemaciclib in solid tumor patients with confirmed MTAP loss. In the Phase 2 expansion part of the study, 6 arms defined by confirmed tumor types will enroll in parallel at the RP2D(s) of TNG456 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

Arms & interventions

  • DrugTNG456

    A selective PRMT5 inhibitor

  • Drugabemaciclib

    A kinase inhibitor

Outcome measures

Primary

  • Phase 1 Maximum Tolerated Dose

    To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib

    Time frame: 21 days

  • 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

    Time frame: 18 weeks

  • 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

    Time frame: 18 weeks

Secondary

  • Phase 1 Anti-neoplastic Activity Single Agent

    Time frame: 18 weeks

  • Phase 1 and 2 Adverse Event Profile

    Time frame: 21 days

  • Phase 1 and 2 Concentration versus Time Curve

    Time frame: 16 days

  • Phase 1 and 2 Time to Achieve Maximal Plasma Concentration

    Time frame: 16 days

  • Phase 1 and 2 Maximum Observed Plasma Concentration

    Time frame: 16 days

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (15)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5452

Recruiting
Mitesh Borad, MD · Principal Investigator

University of California, Irvine

Irvine, California, 92686

Recruiting
Cathleen Park, MD · Principal Investigator

University of California Los Angeles

Los Angeles, California, 90995

Recruiting
Timothy Cloughesy, MD · Principal Investigator

University of California at San Francisco

San Francisco, California, 94143-2202

Recruiting
Nicolas Butowski, MD · Principal Investigator

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016

Recruiting
Solmaz Sahebjam, MD · Principal Investigator

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224

Recruiting
Hani Babiker, MD · Principal Investigator

Northwestern Memorial Hospital

Chicago, Illinois, 60611-2908

Recruiting
Ditte Primdahl, MD · Principal Investigator

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
Jia Luo, MD · Principal Investigator

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905-0001

Recruiting
Kaushal Parikh, MD · Principal Investigator

NYU Langone Health

New York, New York, 10016

Recruiting
Salman Punekar, MD · Principal Investigator

Memorial Sloan Kettering Cancer Center

New York, New York, 11065

Recruiting
Lauren Schaff, MD · Principal Investigator

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

Recruiting
Dwight Owen, MD · Principal Investigator

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Jordi Rodon, MD · Principal Investigator

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112-5500

Recruiting
Howard Coleman, MD · Principal Investigator

NEXT Virginia

Fairfax, Virginia, 22031

Recruiting
Alexander Spira, MD, PhD · Principal Investigator