Retifanlimab With or Without Difluoromethylornithine for the Treatment of Progressive High Grade Gliomas

NCT07468136 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MC230718NCI-2026-0139224-000432
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial tests the safety, side effects best dose and effect of retifanlimab with or without difluoromethylornithine (DFMO) for the treatment of high grade gliomas that are growing, spreading, or getting worse (progressive). Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. DFMO is in a class of medications called ornithine decarboxylase (ODC) inhibitors. It works by blocking the action of a substance that signals tumor cells to multiply. This helps stop or slow the spread of tumor cells. Giving retifanlimab with or without DFMO mat be safe, tolerable and/or effective in treating patients with progressive high grade glioma.

Conditions

Astrocytoma, IDH-Mutant, Grade 3; Malignant Glioma; Anaplastic Oligodendroglioma; Astrocytoma, IDH-Mutant, Grade 4; Diffuse Astrocytoma; Glioblastoma, IDH-Wildtype

Outcome Measures

Primary Outcomes (2)

• Best tolerable dose level of Difluoromethylornithine (DFMO, or eflornithine) (phase I)

  Will use a modified Bayesian Optimal Interval phase I/II (BOIN12) trial design to identify a dose level that is tolerable and has sufficient/optimal pharmacodynamic effects \[e.g., maximum tolerated dose (MTD)\]. Will evaluate toxicity up front to determine dose levels that have acceptable tolerability. Both dose limiting toxicity and pharmacodynamic activity will be used to identify the best dose to bring forward for the phase IIa portion.

  Up to 5 years

• Change in T cell/myeloid cell ratio (phase IIa)

  Will use a log2 transformation of this percentage measure. Will summarize this within each of the treatment arms, and will compare these measures between arms using a two-sample t-test or a nonparametric Wilcoxon rank sum test if not sufficiently normally distributed.

  From baseline up to 5 years

Secondary Outcomes (5)

• T cell/myeloid cell ratio

  From baseline up to 5 years

• Myeloid cell abundance

  Up to 5 years

• Extracellular cytokines/ chemokines

  Up to 5 years

• Incidence of adverse events (AE)

  Up to 5 years

• Progression free survival (PFS)

  Up to 5 years

Study Arms (3)

Group A (retifanlimab and DFMO then surgery)

EXPERIMENTAL

Patients receive retifanlimab IV, over 30 minutes on day 1 of cycle 1 and DFMO PO Q8H on days 1-14 of cycle 1 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care resection surgery. Patients then receive retifanlimab IV, over 30 minutes, on day 1 of each cycle and DFMO PO Q8H on days 1-14 of each cycle. Cycles repeat every 28 days for 16 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI and blood sample collection throughout the study and may optionally undergo CSF fluid collection with or without lumbar puncture.

Procedure: Biospecimen Collection; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Biological: Retifanlimab; Procedure: Tumor Resection

Group B1 (retifanlimab only then surgery)

EXPERIMENTAL

Patients receive retifanlimab IV, over 30 minutes, on day 1 of cycle 1. Patients then undergo standard of care resection surgery. Patients then receive retifanlimab IV, over 30 minutes, on day 1 of each cycle and DFMO PO Q8H on days 1-14 of each cycle. Cycles repeat every 28 days for 16 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI and blood sample collection throughout the study and may optionally undergo cerebrospinal fluid collection with or without lumbar puncture.

Procedure: Biospecimen Collection; Drug: Eflornithine; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Tumor Resection

Group B2 (retifanlimab and DFMO then surgery)

EXPERIMENTAL

Patients receive retifanlimab IV, over 30 minutes on day 1 of cycle 1 and DFMO PO Q8H on days 1-14 of cycle 1, in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care resection surgery. Patients then receive retifanlimab IV, over 30 minutes, on day 1 of each cycle and DFMO PO Q8H on days 1-14 of each cycle. Cycles repeat every 28 days for 16 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI and blood sample collection throughout the study and may optionally undergo cerebrospinal fluid collection with or without lumbar puncture.

Procedure: Biospecimen Collection; Drug: Eflornithine; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Biological: Retifanlimab; Procedure: Tumor Resection

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and CSF collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Group A (retifanlimab and DFMO then surgery); Group B1 (retifanlimab only then surgery); Group B2 (retifanlimab and DFMO then surgery)

Eflornithine DRUG

Given PO

Also known as: Alpha-Difluoromethylornithine, DFMO, Difluoromethylornithine, Difluromethylornithine

Group B1 (retifanlimab only then surgery); Group B2 (retifanlimab and DFMO then surgery)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Group A (retifanlimab and DFMO then surgery); Group B1 (retifanlimab only then surgery); Group B2 (retifanlimab and DFMO then surgery)

Retifanlimab BIOLOGICAL

Given IV

Also known as: INCMGA 0012, INCMGA-0012, INCMGA00012, INCMGA0012, MGA 012, MGA-012, MGA012, Retifanlimab-dlwr, Zynyz

Group A (retifanlimab and DFMO then surgery); Group B2 (retifanlimab and DFMO then surgery)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Group A (retifanlimab and DFMO then surgery); Group B1 (retifanlimab only then surgery); Group B2 (retifanlimab and DFMO then surgery)

Tumor Resection PROCEDURE

Undergo resection surgery

Group A (retifanlimab and DFMO then surgery); Group B1 (retifanlimab only then surgery); Group B2 (retifanlimab and DFMO then surgery)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Diagnosis of high-grade glioma, including any of the following:
• Glioblastoma, IDH-wild type (WT)
• Grade 3 or 4 IDH1/2 mutant astrocytoma or
• Grade 3 oligodendroglioma
• Any prior grade 2 astrocytoma or oligodendroglioma that is suspected to have recurred at a higher grade
• Other high-grade glioma
• Plan for surgical resection as part of routine clinical care
• Radiographic disease progression, with or without tissue confirmation
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2 and Karnofsky Performance Status (KPS) ≥ 60
• NOTE: PS must be assessed (again) within 7 days prior to first dose of study drug
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 15 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 15 days prior to registration)
• Platelet count ≥ 100,000/mm\^3 (obtained ≤ 15 days prior to registration)

You may not qualify if:

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception
• Uncontrolled intercurrent illness that by the judgement of the investigator would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the regimens including, but not limited to:
• ongoing or active infection (e.g., pneumonia, sepsis, etc.) requiring systemic therapy
• current diagnosis or previous history of immune-related (non-infectious) pneumonitis or interstitial lung disease that requires or required steroids
• active autoimmune disease that required systemic treatment other than replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroids) ≤ 2 years prior to registration
• symptomatic congestive heart failure
• unstable angina pectoris
• psychiatric illness/social situations that would limit compliance with study requirements (e.g., drug addiction)
• concurrent active Hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] positive and/or detectable hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\]) and Hepatitis C virus (defined as anti-hepatitis C virus \[HCV\] antibody \[Ab\] positive and detectable HCV ribonucleic acid \[RNA\]) infection
• EXCEPTIONS:
• Patients with evidence of hepatitis B virus (HBV) infection (HBsAg positive) must have completed at least 4 weeks of HBV antiviral therapy, and the HBV viral load must be undetectable at the time of registration
• Patients with a history of hepatitis C virus (HCV) are eligible if they have an undetectable HCV viral load. Patients must have completed curative anti-viral treatment ≥ 4 weeks prior to registration.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Oligodendroglioma; Astrocytoma; Lymphoma, Follicular; Glioblastoma; Glioma

Interventions

Specimen Handling; Eflornithine; Spinal Puncture; Magnetic Resonance Spectroscopy; Transurethral Resection of Bladder

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Terence C. Burns, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients are assigned to group A or B. Patients in group B are randomized to 1 of 2 arms (group B1 or B2)

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: March 12, 2026
• Study Start: April 24, 2026
• Primary Completion (Estimated): October 25, 2030
• Study Completion (Estimated): October 25, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)