A Multicenter Trial to Identify Optimal Atezolizumab Biomarkers in the Setting of Recurrent Glioblastoma. The MOAB Trial

NCT06069726 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Pro00113395
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

Brief Summary

This is to study if neoadjuvant atezolizumab therapy is beneficial for patients with recurrent glioblastoma and a low mutational burden.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Median survival within the low and high TMB groups

  Survival of the prospectively treated patient is defined as the time between initiation of atezolizumab and death. If the patient is alive at the time of analysis, survival will be censored at the time of last follow-up.

  Day 1 of atezolizumab treatment until death or off study due to any other reason whichever comes first, assessed for up to 24 months. If the patient is alive at the time of analysis, survival will be censored at the time of last follow-up.

• Median survival within the low and high TMB groups and their respective matched historical control group

  For comparisons between prospectively treated patients and their matched historical control groups, OS for prospectively treated patients will be measured from the date of atezolizumab until death or last contact. Survival for the matched group is defined as the time between the date of 1st recurrence and death or last contact.

  Day 1 of atezolizumab treatment until death or off study due to any other reason whichever comes first, assessed for up to 24 months. If the patient is alive at the time of analysis, survival will be censored at the time of last follow-up.

Secondary Outcomes (2)

• Proportion of patients that experience grade 3, 4, or 5 adverse events that are possibly, probably, or definitely related to atezolizumab.

  Day 1 of treatment until 30 days post last dose

• Compare Progression Free Survival (PFS) using mRANO criteria between low vs high TMB arms and between TMB-matched historical control arms (low and high TMB)

  Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed for up to 24 months. If patient is alive at the time of analysis, survival will be censored at the time of last follow-up.

Study Arms (1)

Pre-Surgery Atezolizumab

EXPERIMENTAL

80 patients with rGBM who are eligible for surgical debulking will be treated with one dose of atezolizumab prior to resection. Resected tissue will be used to pathologically confirm recurrence, and tumor tissue will be analyzed by whole exome sequencing (WES). Anticipating that40 patients with low TMB and 40 with high TMB will be treated. All treated subjects will receive post-operative atezolizumab until progression, unacceptable toxicity, death or withdrawal of consent. Post-atezolizumab survival will be compared between low vs high TMB arms to determine if low TMB associates with longer survival after atezolizumab

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

One dose of atezolizumab will be given prior to resection.

Pre-Surgery Atezolizumab

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 old
• Pathologically confirmed GBM, IDHwt
• Clinical or radiologic evidence of first or second recurrence following radiation and TMZ. Note: A diagnostic biopsy is required prior to the commencement of the study drug if there is uncertainty about the MRI findings being true progression versus pseudoprogression.
• Tissue available from initial diagnosis of primary GBM
• Adequate organ function:
• Hemoglobin ≥ 9 g/dl
• Platelet count ≥ 75,000/µl
• Neutrophil count ≥ 1000 cells/mm3
• Creatinine ≤ 1.5 x ULN (calculated using the Cockcroft-Gault formula)
• Total bilirubin ≤ 1.5 x ULN (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
• Alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN)
• AST and ALT ≤ 2.5 x ULN
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• Prothrombin and Partial Thromboplastin Times ≤ 1.2 x ULN
• Karnofsky Performance Status (KPS) ≥ 70%

You may not qualify if:

• Pregnancy or breastfeeding or intention of becoming pregnant during study treatment or within 5 months of final dose of atezolizumab therapy
• a) For women of childbearing potential: Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods as defined below: i) Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final dose of atezolizumab. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• ii) A woman is of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
• b) For men with pregnant female partners and/or with female partners of childbearing potential: Agree to remain abstinent (refrain from heterosexual intercourse) or use a condom and refrain from donating sperm.
• i) With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period for 5 months after the final dose of atezolizumab to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.
• Prior treatment with immunotherapy
• Prior treatment with bevacizumab within 4 weeks before biopsy. Note: Bevacizumab will be permitted if necessary to control inflammatory side effects 5-7mg/kg Q 3/52 for up to 3 cycles
• Treatment with systemic immunosuppressive medication (including, but not limited to, more than 2 mg of dexamethasone or equivalent corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
• Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
• Active autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix E in Section 16.5 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.

Sponsors & Collaborators

• Duke University: lead

Study Sites (4)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

ACTIVE NOT RECRUITING

Duke University

Durham, North Carolina, 27705, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

atezolizumab

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

Study Officials

• Mustafa Khasraw, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mustafa Khasraw, MD

CONTACT

919 684 5301; mustafa.khasraw@duke.edu

Monika Anand, PhD

CONTACT

919 661 8838; monika.anand@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurosurgery

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: October 6, 2023
• Study Start: March 21, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)