Safety and Tolerability of TNG456 Alone and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss
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
1 other identifier
interventional
191
1 country
15
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2025
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 24, 2025
CompletedFirst Posted
Study publicly available on registry
February 5, 2025
CompletedStudy Start
First participant enrolled
March 24, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2027
April 13, 2026
April 1, 2026
2 years
January 24, 2025
April 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase 1 Maximum Tolerated Dose
To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib
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
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
18 weeks
Secondary Outcomes (5)
Phase 1 Anti-neoplastic Activity Single Agent
18 weeks
Phase 1 and 2 Adverse Event Profile
21 days
Phase 1 and 2 Concentration versus Time Curve
16 days
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
16 days
Phase 1 and 2 Maximum Observed Plasma Concentration
16 days
Study Arms (7)
Single Agent and Combination Dose Escalation
EXPERIMENTALSolid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD
NSCLC Single Agent Dose Expansion
EXPERIMENTALNSCLC (squamous and non squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
GBM Single Agent Dose Expansion
EXPERIMENTALGBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
Tumor Agnostic Single Agent Dose Expansion
EXPERIMENTALPatients with specific solid tumor types that have a confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
NSCLC Combination Expansion
EXPERIMENTALNSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
GBM Combination Expansion
EXPERIMENTALGBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
Tumor Agnostic Combination Expansion
EXPERIMENTALParticipants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
Interventions
A kinase inhibitor
A selective PRMT5 inhibitor
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tango Therapeutics, Inc.lead
- Eli Lilly and Companycollaborator
Study Sites (15)
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5452, United States
University of California, Irvine
Irvine, California, 92686, United States
University of California Los Angeles
Los Angeles, California, 90995, United States
University of California at San Francisco
San Francisco, California, 94143-2202, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611-2908, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905-0001, United States
NYU Langone Health
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 11065, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112-5500, United States
NEXT Virginia
Fairfax, Virginia, 22031, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Tab Cooney, MD
Tango Therapeutics, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2025
First Posted
February 5, 2025
Study Start
March 24, 2025
Primary Completion (Estimated)
March 31, 2027
Study Completion (Estimated)
September 30, 2027
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share