Novel Indenoisoquinolone CMYC/TOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma

NCT07416188 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002185002185-N
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Glioblastoma is a common brain cancer in adults. Treatment includes surgery, radiation, and chemotherapy. But this cancer can return after treatment and is often fatal. Researchers want to know if a study drug (LMP744) can kill glioblastoma tumor cells. Objective: To test LMP744 in people with glioblastoma. Eligibility: People aged 18 years or older with glioblastoma that returned after treatment. Design: Participants will be screened. They will have a surgery to remove a small sample of tumor tissue (biopsy) from the brain. This will be done under protocol 03-N-0164. They will stay in the clinic for 1 night. They will also have imaging scans and tests of their heart function. Participants will have a central line installed: A flexible tube will be inserted into a vein in the chest. It will be attached to a port under the skin. This port will be used to draw blood and give medicines without having to insert new needles into a vein. LMP744 will be given through the central line for 5 days in a row. Participants will remain in the clinic for this time. Participants will then have a second surgery to remove as much of their tumor as possible. They will remain in the clinic until they recover from the surgery. Then they will recover at home after surgery. Participants will return to the clinic to receive the study drug for 5 days in a row through the central line, once a month for up to 12 months. Blood tests, heart function tests, and periodic imaging scans will be repeated during these visits. Participants will continue to have telehealth visits every 3 months after they stop taking the drug.

Conditions

Brain and Central Nervous System Tumors; Glioma; Glioblastomas; Brain Cancer; Recurrent Glioblastoma; Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype; Relapsed Cancer; Recurrent Tumor; Glioblastoma Multiforme; Recurring Glioblastoma; GBM; Grade IV Astrocytoma; Recurrent Glioma (Glioblastoma Multiforme); High Grade Glioma; Glioma, Malignant

Keywords

Recurrent Glioblastoma; Glioma; Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histological Type; Glioblastoma Multiforme (GBM); Phase I; Phase II; Brain Cancer

Outcome Measures

Primary Outcomes (1)

• Partial response (>=50% disease reduction) or complete response (100% disease reduction) based on RANO 2.0 criteria

  As ORR is associated with survival experience, this endpoint allows for objective evaluation of efficacy of LMP744 in this proof-of-concept phase 2 trial

  5 years

Secondary Outcomes (4)

• Progression-Free Survival (PFS): Time from the start of treatment with LMP744 until disease progression based on RANO 2.0 criteria

  5 years

• Overall Survival (OS): Time from the start of treatment with LMP744 until death from any cause

  5 years

• Changes in transcriptomic and proteomic profiles before and after LMP744 treatment

  5 years

• Change in self-reported quality of life (QOL) as measured by the SF-36 survey at baseline, after each treatment cycle, and at study completion.

  5 years

Study Arms (1)

Arm A

EXPERIMENTAL

All patients will receive LMP744 as the interventional drug along with surgery for a biopsy and a second surgery for either resection or an additional biopsy to compare the tissue pre vs. post-drug treatment.

Drug: LMP744; Procedure: Conventional Surgery or Biopsy

Interventions

LMP744 DRUG

Indenoisoquinolone C-MYC/TOPOISOMERASE 1 Inhibitor

Arm A

Conventional Surgery or Biopsy PROCEDURE

Conventional Surgery or Biopsy

Arm A

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants \>= 18 years of age
• Tissue-based diagnosis of recurrent glioblastoma, IDH-wildtype by a neuropathologist
• Karnofsky Performance Status (KPS) \>60
• Willing to use effective birth control method
• The effects of LMP744 on developing human fetuses are unknown. Therefore, females of childbearing potential and their male partners must be willing to use an effective method of contraception during the clinical study (hormonal, barrier, surgical, or abstinence) before study enrollment and for 6 months after the last dose of the study drug. If the female becomes pregnant or suspects she is pregnant while participating in this study, she must inform her treating physician immediately.
• Agreeable to undergo craniotomy for brain biopsy and/or resection
• Initial diagnostic biopsy under 03-N-0164 to confirm recurrent disease and obtain pre-treatment tissue. Only participants who were not expected to able to achieve a gross total resection of tumor will be included in the study.
• Willing and able to appoint a durable power of attorney
• Able to provide informed consent or have a legally authorized representative (LAR) to provide consent, if incapacitated.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnant and/or nursing females
• As LMP744 is a novel agent with the potential for teratogenic or abortifacient effects, pregnant and/or nursing females will be excluded from receiving drug
• Significant medical co-morbidities that would compromise the participant s ability to tolerate LMP744 and which cannot reasonably be controlled (per the investigator s judgment, such as poorly controlled chronic kidney disease and/or poorly controlled congestive heart failure)
• Social situations that would limit compliance with study requirements, such as chronic homelessness
• Prior chemotherapy or biologic therapy completed within 4 weeks (6 weeks for nitrosoureas and mitomycin C) or a duration of 5 half-lives (whichever is shorter)
• Additional malignancy diagnosed or requiring active treatment within 1 year of screening
• Unable to undergo an MRI scan of the brain
• Active autoimmune disease that requires systemic treatment within 2 years of screening
• Cardiac disease
• \>=2 MIs
• \>=2 coronary revascularization procedures
• Cardiac Troponin T or I \>= 2x the institutional upper limit of normal at screening
• Ejection fraction \<45% on screening echocardiogram
• Chronic hypokalemia (K\<2.5 mmol/L)

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioblastoma; Recurrence; Central Nervous System Neoplasms; Glioma; Brain Neoplasms; Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Sadhana Jackson, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sadhana Jackson, M.D.

CONTACT

(301) 594-7037; sadhana.jackson@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2026
• First Posted: February 18, 2026
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2032
• Last Updated: April 16, 2026

Record last verified: 2026-03-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Study protocol will be shared as requested. CSR will be shared at the time the CSR is due.
• Access Criteria: De-identified IPD will be shared with the CRADA partner through the EDC.

Locations

US (1)