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Safety and Feasibility of First-line Avutometinib and Defactinib in Patients With Newly Diagnosed High-grade Gliomas

NCT07778602 · Status: NOT_YET_RECRUITING · Phase: EARLY_PHASE1 · Type: INTERVENTIONAL · Enrollment: 22

Last updated 2026-08-26

No results posted yet for this study

Summary

This clinical trial is designed with two treatment stages: Stage 1: one cycle of study drug treatment prior to initiation of first-line standard radiation in all study participants. Stage 2: two additional cycles of study drug treatment (8 weeks total) concomitantly with standard of care radiation (\~6 weeks) for participants with pathology-confirmed MGMT (enzyme O-6-methylguanine-DNA methyltransferase) unmethylated GBM only.

The co-primary endpoints of the study are 1) feasibility of completing Stage 1 of treatment prior to radiation in all study participants and starting radiation within 6 weeks, and 2) safety of study drug across both treatment parts. The investigators will additionally evaluate the radiographic response rate after the first cycle of drug in all patients based upon RANO 2.0 (Response Assessment in Neuro-Oncology) criteria as well as safety of study drug in all patients (secondary endpoints). Exploratory endpoints will include characterization of ERK (extracellular signal-regulated kinase) and FAK (Focal adhesion kinase) dependence in pre-treatment tissue (by immunohistochemistry and/or 'omics) and correlation of expression and co-mutations with response and survival.

A total of up to 22 evaluable patients can be enrolled in this study. Evaluable patients are those who have received at least one dose of study drug treatment. Patients who do not start drug will be replaced, up to a total of 28 patients.

Conditions

  • MGMT-unmethylated Glioblastoma (GBM)
  • IDH Wildtype Glioblastoma

Interventions

DRUG

avutometinib and defactinib for 3 weeks on/1 week off

avutometinib 3.2 mg orally twice weekly and defactinib 200 mg orally twice a day for 3 weeks on/1 week off (one cycle = 4 weeks total)

DRUG

MGMT-unmethylated GBM with Radiation

Patients whose final pathology is MGMT promoter unmethylated GBM will receive an additional 2 cycles of avutometinib/defactinib concurrently with radiation (without temozolomide).

Sponsors & Collaborators

  • Keep Punching Foundation

    collaborator UNKNOWN

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    lead OTHER

Principal Investigators

  • Karisa C Schreck, MD, PhD · Johns Hopkins University

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SEQUENTIAL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-11-10
Primary Completion
2028-11-10
Completion
2029-12-23
FDA Drug
Yes

Countries

  • United States
  • Puerto Rico

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07778602 on ClinicalTrials.gov