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

NCT ID: NCT06810544

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

191 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-24

Study Completion Date

2027-09-30

Brief Summary

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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

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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.

Conditions

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Non Small Cell Lung Cancer Glioma Glioblastoma Multiforme Glioma, Malignant Solid Tumor Non-Small Cell Adenocarcinoma Lung Cancer Brain Tumor

Keywords

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MTAP PRMT5 inhibitor CDK 4/6 abemaciclib Tango

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Phase 1 dose escalation (sequential) followed by phase 2 dose expansion (parallel)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

TNG456

Intervention Type DRUG

A selective PRMT5 inhibitor

abemaciclib

Intervention Type DRUG

A kinase inhibitor

NSCLC Single Agent Dose Expansion

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

Group Type EXPERIMENTAL

TNG456

Intervention Type DRUG

A selective PRMT5 inhibitor

GBM Single Agent Dose Expansion

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

Group Type EXPERIMENTAL

TNG456

Intervention Type DRUG

A selective PRMT5 inhibitor

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)

Group Type EXPERIMENTAL

TNG456

Intervention Type DRUG

A selective PRMT5 inhibitor

NSCLC Combination Expansion

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

Group Type EXPERIMENTAL

TNG456

Intervention Type DRUG

A selective PRMT5 inhibitor

abemaciclib

Intervention Type DRUG

A kinase inhibitor

GBM Combination Expansion

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

Group Type EXPERIMENTAL

TNG456

Intervention Type DRUG

A selective PRMT5 inhibitor

abemaciclib

Intervention Type DRUG

A kinase inhibitor

Tumor Agnostic Combination Expansion

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

Group Type EXPERIMENTAL

TNG456

Intervention Type DRUG

A selective PRMT5 inhibitor

abemaciclib

Intervention Type DRUG

A kinase inhibitor

Interventions

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TNG456

A selective PRMT5 inhibitor

Intervention Type DRUG

abemaciclib

A kinase inhibitor

Intervention Type DRUG

Other Intervention Names

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Verzenio

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Tango Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maeve Waldron-Lynch, MD

Role: STUDY_DIRECTOR

Tango Therapeutics, Inc.

Locations

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Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status RECRUITING

Sibley Memorial Hospital

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

Site Status RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maeve Waldron-Lynch, MD

Role: CONTACT

Phone: (857) 320-4899

Email: [email protected]

Other Identifiers

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TNG456-C101

Identifier Type: -

Identifier Source: org_study_id