Carmustine Wafer in Combination With Retifanlimab and Radiation With/Without Temozolomide in Subjects With Glioblastoma

NCT05083754 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: J21103IRB00291102
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the safety and survival of carmustine wafers and radiation and retifanlimab with or without temozolomide (TMZ) in newly-diagnosed adult subjects with glioblastoma multiform after carmustine wafer placement.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (3)

• Safety of combination retifanlimab and radiation with and without temozolomide as assessed by number of participants who experience adverse events

  Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

  Up to 2 years

• Feasibility of combination retifanlimab and radiation with and without temozolomide as assessed by number of participants who experience adverse events

  Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

  Up to 2 years

• Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT)

  Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE).

  Up to 2 years

Secondary Outcomes (4)

• Safety as assessed by number of treatment-emergent adverse events in patients on combination refitanlimab and standard of care (SOC) with newly diagnosed glioblastoma after treatment with carmustine wafers

  Up to 2 years

• Progression Free Survival

  Up to 2 years

• Overall Response Rate

  Upt to 2 years

• Overall Survival

  Up to 2 years

Other Outcomes (12)

• Tumor Response as assessed by immune markers in tumor and blood samples

  Up to 2 years

• Biomarker assessment in tumor and blood samples

  Up to 2 years

• Microsatellite instability (MSI) assessment

  Up to 2 years

Study Arms (3)

Arm A- Retifanlimab and Radiation Therapy

EXPERIMENTAL

Participants will receive Retifanlimab and Radiation Therapy.

Drug: Retifanlimab; Radiation: Radiation Therapy

Arm B- Retifanlimab, Radiation Therapy and Temozolomide

EXPERIMENTAL

Participants will receive Retifanlimab, Radiation Therapy and Temozolomide.

Drug: Retifanlimab; Drug: Temozolomide; Radiation: Radiation Therapy

Arm C- Radiation Therapy and Temozolomide

OTHER

Participants will receive Radiation Therapy and Temozolomide which is the Standard of Care.

Drug: Temozolomide; Radiation: Radiation Therapy

Interventions

Radiation Therapy RADIATION

Standard of Care

Arm A- Retifanlimab and Radiation Therapy; Arm B- Retifanlimab, Radiation Therapy and Temozolomide; Arm C- Radiation Therapy and Temozolomide

Retifanlimab DRUG

Anti-PD-1 Therapy

Also known as: INCMGA00012

Arm A- Retifanlimab and Radiation Therapy; Arm B- Retifanlimab, Radiation Therapy and Temozolomide

Temozolomide DRUG

Anti-PD-1 Therapy

Arm B- Retifanlimab, Radiation Therapy and Temozolomide; Arm C- Radiation Therapy and Temozolomide

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly-diagnosed adults with WHO (World Health Organization) Grade IV Glioblastoma or gliosarcoma based on histopathological or molecular criteria who had carmustine wafers placed at resection
• No prior treatment for GBM other than surgical resection and carmustine wafer placement (Patients who had a biopsy prior to resection are allowed)
• Post-operative MRI or CT scan within 72 hours (preferably 24 hours) of surgical resection
• Substantial recovery from surgical resection
• On a stable or decreasing dose of steroids
• Karnofsky Performance Status of ≥ 60
• Clinically appropriate for concomitant temozolomide plus radiation therapy (RT) based on institutional guidelines
• Age ≥18 years
• Ensure that pregnant or lactating females are not enrolled and that contraceptive requirements are in accordance with applicable and recent requirements.
• Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 180 days after the last dose of retifanlimab
• Must have normal organ and marrow function on routine laboratory tests
• Ability to understand and the willingness to sign a written informed consent document
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, study procedures, and other requirements of the study

You may not qualify if:

• Recurrent glioblastoma (GBM) or progression of lower grade tumor
• Central nervous system (CNS) hemorrhage of Grade \> 1 on baseline MRI scan, unless subsequently documented to have resolved
• Any known metastatic extracranial or leptomeningeal disease
• Intent to use other anti-neoplastic medications/treatments including the Optune® device
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Active, known or suspected autoimmune disease, with the following exceptions: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment (subjects with a history of flares requiring systemic treatment are excluded), or other autoimmune conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Subjects with history of life-threatening toxicity, including hypersensitivity reaction, related to prior immunoglobulin treatment for another condition (except those considered unlikely to re-occur, with written approval of study PI) or any other study drug component
• History or evidence upon physical/neurological examination of other central nervous system condition (e.g., seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment
• Surgical procedure \< 7 days prior to study treatment (No restriction for insertion of a central venous access device)
• Unable to swallow oral medication or any gastrointestinal disease or surgical procedure that may seriously impact the absorption of temozolomide
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, totally excised melanoma of stage IIA or lower, low or intermediate-grade localized prostate cancer (Gleason score ≤ 7), and curatively-treated carcinoma in situ of the cervix, breast, or bladder.
• Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Incyte Corporation: collaborator

Study Sites (1)

Johns Hopkins Medical Institution

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Radiotherapy

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Lawrence Kleinberg, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lawrence Kleinberg, MD

CONTACT

410-614-2597; kleinla@jhmi.edu

Ipshita Faldu

CONTACT

667-306-8336; ifaldu1@jhu.edu

Study Design

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

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 19, 2021
• Study Start: August 31, 2022
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)