Retifanlimab with Bevacizumab and Hypofractionated Radiotherapy for the Treatment of Recurrent Glioblastoma

NCT06160206 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: ACCRU-NO-2301NCI-2023-09550P30CA015083
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests how well retifanlimab with bevacizumab and hypofractionated radiotherapy, compared to bevacizumab and hypofractionated radiotherapy alone, works in treating patients with glioblastoma that has come back after a period of improvement (recurrent). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). 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. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving retifanlimab with bevacizumab and hypofractionated radiotherapy may work better in treating patients with recurrent glioblastoma than bevacizumab and hypofractionated radiotherapy alone.

Conditions

Recurrent Glioblastoma; Recurrent WHO Grade 4 Glioma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Defined as the proportion of patients who are alive 9 months after randomization based on Kaplan Meier estimate. The proportion of patients alive will be compared between treatment arms using a z-score test statistic. The 9-month OS Kaplan Meier estimate and corresponding 95% confidence interval for each arm will be reported.

  Time until death from any cause, assessed up to 9 months after registration

Secondary Outcomes (5)

• OS

  Up to 4 years after registration

• Progression free survival (PFS)

  Up to 4 years after registration

• Objective response rate (ORR)

  Up to 4 years after registration

• Neurologic function domain scores

  Up to 2 months after registration

• Incidence of adverse events

  Up to 4 years after registration

Study Arms (2)

Arm A (Retifanlimab, bevacizumab and HFRT)

EXPERIMENTAL

ARM I: Patients receive retifanlimab IV over 30 minutes on day 1 and bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Electronic Health Record Review; Radiation: Hypofractionated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Biological: Retifanlimab

Arm B (Bevacizumab and radiation)

EXPERIMENTAL

Patients receive bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Electronic Health Record Review; Radiation: Hypofractionated Radiation Therapy; Procedure: Magnetic Resonance Imaging

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, CT-P16, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, MYL-1402O, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

Arm A (Retifanlimab, bevacizumab and HFRT); Arm B (Bevacizumab and radiation)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Arm A (Retifanlimab, bevacizumab and HFRT); Arm B (Bevacizumab and radiation)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Arm A (Retifanlimab, bevacizumab and HFRT); Arm B (Bevacizumab and radiation)

Electronic Health Record Review OTHER

Ancillary studies

Arm A (Retifanlimab, bevacizumab and HFRT); Arm B (Bevacizumab and radiation)

Hypofractionated Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Hypofractionated, Hypofractionated Radiotherapy, hypofractionation, Radiation, Hypofractionated

Arm A (Retifanlimab, bevacizumab and HFRT); Arm B (Bevacizumab and radiation)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

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

Arm A (Retifanlimab, bevacizumab and HFRT); Arm B (Bevacizumab and radiation)

Retifanlimab BIOLOGICAL

Given IV

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

Arm A (Retifanlimab, bevacizumab and HFRT)

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
• Recurrent World Health Organization (WHO) grade IV glioblastoma. Note: Any number of recurrences are allowable. Glioblastoma (GBM) variants and molecular GBM are allowed
• Candidates for radiotherapy
• Prior use of bevacizumab is allowed as long as the last treatment is \> 4 months prior to randomization
• Dexamethasone dose ≤ 4mg daily at the time of randomization (higher dose of steroid for symptom control is allowed during the study)
• Karnofsky performance status ≥ 60%
• Measurable disease or non-measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 (obtained ≤ 28 days prior to registration)
• NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the Academic and Community Cancer Research Untied (ACCRU) website under "General Forms"
• Platelet count ≥ 100,000/mm\^3 (obtained ≤ 28 days prior to registration)
• NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 28 days prior to registration)
• NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 28 days prior to registration)
• NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception (men and women)
• Co-morbid systemic illness or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Receiving any other investigational agent which would be considered treatment for the primary neoplasm ≤ 2 weeks prior to registration
• Active uncontrolled autoimmune disease or syndrome (i.e. moderate or severe rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, active inflammatory bowel disease) that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) or who are receiving systemic therapy for an autoimmune or inflammatory disease (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Subjects are permitted to enroll if they have vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Has a severe acute or chronic medical condition including immune colitis, inflammatory bowel disease (may be enrolled at the discretion of the principal investigator \[PI\]), immune pneumonitis, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to epacadostat, retifanlimab, bevacizumab, or other agents used in the study
• Has had an allogeneic tissue/solid organ transplant
• Has uncontrolled human immunodeficiency virus (HIV) (HIV ½ antibodies). Well-controlled HIV is defined as CD4+ count \> 300 cells, undetectable viral load, and receiving highly active antiretroviral therapy (HAART)/antiretroviral therapy (ART). Study specific HIV testing is not required for patients who do not have any prior history of HIV
• Has uncontrolled active hepatitis B (HBV) (e.g., hepatitis B serum antigen \[HBsAg\] reactive or HBV dioxyribonucleic acid \[DNA\] detected by quant real time polymerase chain reaction \[RT PCR\]) or hepatitis C (e.g. hepatitis C serum antigen \[HCsAg\] reactive or hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative or quantitative\] is detected)
• Receipt of live attenuated vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

ACTIVE NOT RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

ACTIVE NOT RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Specimen Handling; Radiation Dose Hypofractionation; Radiation; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Physical Phenomena; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jian L Campian

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Inbox Mayo Clinic Cancer Studies

CONTACT

507-538-5424; MAYOCLINICCANCERSTUDIES@mayo.edu

Mayo Clinic Cancer Studies

CONTACT

507-266-5822; MAYOCLINICCANCERSTUDIES@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 7, 2023
• Study Start: October 2, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2030
• Last Updated: November 19, 2024

Record last verified: 2024-11

Locations

US (3)