Retifanlimab and Epacadostat in Combination With Radiation and Bevacizumab in Patients With Recurrent Gliomas

NCT03532295 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: 202003050
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 4

Brief Summary

In this study, the investigators propose to combine retifanlimab with radiation therapy (RT) and bevacizumab with or without epacadostat in the treatment of recurrent glioblastoma (GBM). The investigators hypothesize that this combination provides a powerful synergy between RT and immune modulators to produce more robust anti-tumor immune response, induce tumor regression and improve overall survival.

Conditions

Glioma; Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Kaplan-Meier Estimate of Overall Survival (OS) at 9 Months

  Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.

  At 9 months

• Kaplan-Meier Estimate of Overall Survival (OS) at 12 Months

  Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.

  At 12 months

• Median Overall Survival (OS)

  Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.

  Through 2 years after completion of treatment (estimated to be 4 years)

Secondary Outcomes (5)

• Change in Neurologic Functions as Measured by the Neurologic Function in Neuro-Oncology (NANO) Scale

  Screening (mean 9 days, range 1-21 days prior to treatment) & at last assessment (31/49 patients measured at end of treatment, 18 patients' last measurement was on Cycle 2-23 with a mean of 5.8 cycles)

• Safety and Toxicity of Regimen as Measured by Immune Related Grade 3 or Higher Adverse Events Experienced by Participant

  90 days after completion of treatment (estimated to be 2 years and 90 days)

• Kaplan-Meier Estimate of Progression-Free Survival (PFS) at 9 Months

  At 9 months

• Kaplan-Meier Estimate of Progression-Free Survival (PFS) at 12 Months

  At 12 months

• Median Progression-Free Survival (PFS)

  Through 2 years after completion of treatment (estimated to be 4 years)

Study Arms (2)

Regimen A: Retifanlimab+RT+bevacizumab

EXPERIMENTAL

* Retifanlimab will be given intravenously over the course of 30 to 60 minutes at a dose of 500 mg on Day 1 of each 28-day cycle. * Bevacizumab will be given intravenously at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle. * Ten fractions of radiation therapy will be given at a dose of 3.5 Gy per fraction * Retifanlimab and bevacizumab will be started approximately two weeks before the first day of radiation therapy * Treatment may continue for up to two years.

Drug: Bevacizumab; Radiation: Radiation therapy; Drug: Retifanlimab

Regimen B: Retifanlimab+RT+bevacizumab+epacadostat

EXPERIMENTAL

* Retifanlimab will be given intravenously over the course of 30 to 60 minutes at a dose of 500 mg on Day 1 of each 28-day cycle. * Bevacizumab will be given intravenously at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle. * Ten fractions of radiation therapy will be given at a dose of 3.5 Gy per fraction * Retifanlimab and bevacizumab will be started approximately two weeks before the first day of radiation therapy * Epacadostat will be administered orally at 400 mg BID. * Treatment may continue for up to two years.

Drug: Epacadostat; Drug: Bevacizumab; Radiation: Radiation therapy; Drug: Retifanlimab

Interventions

Epacadostat DRUG

-All BID doses will be taken in the morning and evening, approximately 12 hours apart

Regimen B: Retifanlimab+RT+bevacizumab+epacadostat

Bevacizumab DRUG

-The first infusion will be over the course of 90 minutes; if tolerated, the second infusion will be over the course of 60 minutes; if tolerated, all subsequent infusions will be over 30 minutes

Also known as: Avastin

Regimen A: Retifanlimab+RT+bevacizumab; Regimen B: Retifanlimab+RT+bevacizumab+epacadostat

Radiation therapy RADIATION

-The gross tumor maximum diameter (to be irradiated) to be \</= 6 cm in the first 6 patients. If more than 1 target is irradiated, then the sum of all the target maximum diameters should be \</= 6 cm. No more than 3 separate targets for RT is allowed.

Regimen A: Retifanlimab+RT+bevacizumab; Regimen B: Retifanlimab+RT+bevacizumab+epacadostat

Retifanlimab DRUG

-Will be supplied by Incyte

Also known as: INCMGA00012

Regimen A: Retifanlimab+RT+bevacizumab; Regimen B: Retifanlimab+RT+bevacizumab+epacadostat

Eligibility Criteria

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

You may qualify if:

• Recurrent WHO grade 4 glioblastoma or gliosarcoma, including molecular features of glioblastoma and WHO grade 4 astrocytoma or WHO grade high grade glioma.
• Other GBM variants and "secondary GBM" are allowed. All grade 4 gliomas that have relapsed more than once may be included, as the prognosis of multiply recurrent grade 4 glioma patients may not differ based on IDH mutation status.
• Disease must have recurred, and patient must be a candidate for re-irradiation and bevacizumab. Any number of recurrences are allowed.
• Patients must have measurable disease per RANO criteria. Lesions will be considered measurable when they are bi-dimensional with clearly defined margins of ≥5 mm in two perpendicular diameters.
• Prior transient use of bevacizumab for cerebral edema or radiation necrosis is allowed without a washout period. Prior bevacizumab use is permitted if used for treatment of disease if administered more than 4 months prior to registration.
• At least 18 years of age.
• Karnofsky performance status ≥ 60%
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,000/mcL
• Platelets ≥ 75,000/mcL
• Hemoglobin ≥ 9.0 g/dL or \> 5.6 mmol/L (transfusion is acceptable to meet this criterion)
• Serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault for patients
• Serum total bilirubin ≤ 1.5 ULN
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
• INR or PT ≤ 1.5 x IULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

You may not qualify if:

• Currently receiving any other investigational agents.
• 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.
• Dexamethasone dose \> 4 mg daily at the time of registration (higher dose of steroid for symptom control is allowed during the study).
• History of intracranial abscess within 6 months prior to start of study therapy.
• Has active 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, immune pneumonitis, pulmonary fibrosis, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, 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.
• Has had an allogeneic tissue/solid organ transplant.
• Has an active infection requiring intravenous antibiotic therapy. Has a known history of active tuberculosis (TB; bacillus tuberculosis).
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or IDO inhibitor.
• If a patient is enrolled to regimen B, they are prohibited from receiving monoamine oxidase inhibitors (MAOIs) or drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening.
• If a patient is enrolled to regimen B, the use of any UGT1A9 inhibitor from screening through follow-up period, including acitretin, amitriptyline, androsterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide, gefitinib, gemfibrozil, glycyrrhetinic acid, glycyrrhizin, imatinib, imipramine, ketoconazole, linoleic acid supplements, mefenamic acid, mycophenolic acid, niflumic acid, nilotinib, phenobarbital, phenylbutazone, phenytoin, probenecid, propofol, quinidine, ritonavir, sorafenib, sulfinpyrazone, valproic acid, and verapamil is prohibited.
• If a patient is enrolled to regimen B, the use of probiotics from screening through end of treatment is prohibited.
• If a patient is enrolled to regimen B, the use of warfarin is prohibited. If anti-coagulation is needed during the conduct of the study and non-warfarin regimens are not feasible, the participant must discontinue study therapy.
• Chronic use of systemic antibiotics (\> 14 days) unless medical monitor review and approval.
• Any history of serotonin syndrome (SS) after receiving serotonergic drugs.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Incyte Corporation: collaborator

Study Sites (4)

Mayo Clinic

Phoenix, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

epacadostat; Bevacizumab; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Results Point of Contact

• Title: Dr. Milan Chheda
• Organization: Washington University School of Medicine

mchheda@wustl.edu

314-747-7222

Study Officials

• Milan Chheda, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: May 22, 2018
• Study Start: April 20, 2020
• Primary Completion: July 26, 2024
• Study Completion: October 31, 2025
• Last Updated: November 21, 2025
• Results First Posted: August 7, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)