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Recruiting NCT06810544

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

Phase I / Phase II Interventional Non Small Cell Lung Cancer Glioma Glioblastoma Multiforme Glioma, Malignant Solid Tumor

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: TNG456, abemaciclib.
Who it may be relevant to
Registry conditions: Non Small Cell Lung Cancer, Glioma Glioblastoma Multiforme, Glioma, Malignant, Solid Tumor. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

  • Drug TNG456
    A selective PRMT5 inhibitor
  • Drug abemaciclib
    A kinase inhibitor

Primary outcome measures

  • 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]
Secondary outcome measures (5)
  • 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 15 centers
  • Mayo Clinic Scottsdale — Scottsdale
  • University of California, Irvine — Irvine
  • University of California Los Angeles — Los Angeles
  • University of California at San Francisco — San Francisco
  • Sibley Memorial Hospital — Washington D.C.
  • Mayo Clinic Jacksonville — Jacksonville
  • Northwestern Memorial Hospital — Chicago
  • Dana Farber Cancer Institute — Boston
  • … and 7 more centers

Identifiers

NCT: NCT06810544 · TNG456-C101

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗