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Glioblastoma MultiformePhase 1NCT03961971

Trial of Anti-Tim-3 in Combination With Anti-PD-1 and SRS in Recurrent GBM

A Phase 1 study testing MBG453 in people with Glioblastoma Multiforme, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects of stereotactic radiosurgery with MBG453 and spartalizumab in treating patients with recurrent glioblastoma multiforme (GBM). Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor to more precisely… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma Multiforme
What is being tested?
MBG453
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
2 sitesUnited States
Study dates
18 Feb 2020to 30 Jul 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must provide written informed consent prior to any screening procedures.
  • Age 18 years or older.
  • Willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • Must have WHO Grade IV Glioblastoma or gliosarcoma based on histopathological OR molecular criteria
  • Patients tumor target (GTV) should be ≤ 5 cm.
  • a) Must have received first-line multimodal therapy with surgery (resection or biopsy) followed by radiation and Temozolomide (unless known MGMT promoter unmethylated) AND b) Must have completed at least 21 days of combination and Temozolomide therapy (unless known MGMT promoter unmethylated. . An interval of at least 12 weeks after the end of combination radiation therapy + Temozolomide is required unless there is: i.) Histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field. (*NOTE: Patients treated with Optune device or who received Gliadel wafers placed during the first surgery are eligible.
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  • Must have no more than 2 recurrences of either GBM or gliosarcoma. Recurrence must be confirmed by diagnostic biopsy/surgery with local pathology review OR contrast-enhanced MRI measurable by RANO criteria. (*NOTE: Patients diagnosed with WHO Grade III that undergo surgical resection and are found to have WHO Grade IV or gliosarcoma are considered eligible).
  • Prior gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is allowed but the subject must have either histopathologic confirmation of recurrent tumor, or new enhancement on MRI outside of the radiotherapy treatment field
  • Karnofsky Performance Status ≥ 70
  • Must have ability to undergo MRI scans
  • Must be > 30 days since last chemotherapy
  • Must have recovered from severe toxicity of prior therapy. (NOTE: Patients who undergo surgical resection must have recovered from surgery (at least 2 weeks) before starting study treatment).
  • Subjects must have normal organ and marrow function as defined below:
  • WBC ≥ 2,000/mcL absolute neutrophil count ≥ 1,500/mcL platelets ≥ 100,000/mcL hemoglobin ≥ 9.0 g/dL lymphocytes ≥ 500/mcL total bilirubin ≤ 1.5X institutional upper limit of normal AST/ALT ≤ 3.0 X institutional upper limit of normal creatinine ≤ 1.5X institutional upper limit of normal OR Creatinine clearance (CrCl) ≥ 50 mL/min (using the Cockcroft-Gault formula)
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within -7 days prior to the start of therapy. Women must not be breastfeeding.
  • Women of child bearing potential (WOCBP) and men must use a reliable form of contraception during the study treatment period and for 150 days following the last dose of study drug. In order for a woman to be determined not of child-bearing potential, she must have ≥ 12 months of non-therapy-induced amenorrhea or be surgically sterile.

Who cannot join

  • History of other malignancy, unless the patient has been disease-free for at ≥5 years. Curatively treated basal or squamous cell carcinoma of the skin, totally excised melanoma of stage IIA or lower, low or intermediate-grade localized prostate cancer (Gleason sum ≤7), and curatively-treated carcinoma in situ of the cervix, breast, or bladder are allowed regardless.
  • Any known metastatic extracranial or leptomeningeal disease.
  • Evidence of acute intracranial / intra-tumoral hemorrhage
  • History of organ or hematopoietic stem cell (HSC) transplant
  • Receiving greater than 4 mg dexamethasone/day (or equivalent amount of an alternative corticosteroid) for a minimum of 5 days prior to screening visit. Subjects with an autoimmune condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study entry *NOTE: Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone or equivalent, are permitted in the absence of active autoimmune disease
  • Prior treatment with immune-modulating therapy, other than steroids.
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  • Pregnant or nursing (lactating) women
  • Known positive history of HIV, active Hepatitis B, and/or active Hepatitis C infection.
  • Subjects with active, or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Major surgery, outside of a craniotomy/resection, within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
  • Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment
  • 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.
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • History of evidence upon physical/neurological examination of other central nervous system condition (i.e. seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment.
  • History of allergy or hypersensitivity to study drug components.
  • Prisoners or subjects who are involuntarily incarcerated.
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infections disease) illness.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Stanford University

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase I Trial of Anti-Tim-3 in Combination With Anti-PD-1 and SRS in Recurrent GBM

This phase I trial studies the side effects of stereotactic radiosurgery with MBG453 and spartalizumab in treating patients with recurrent glioblastoma multiforme (GBM). Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor to more precisely target the cancer. Monoclonal antibodies, such as MBG453 and spartalizumab may interfere with the ability of tumor cells to grow and spread. Giving stereotactic radiosurgery together with immunotherapy may be a better treatment for GBM.

Read the detailed description

Primary Objectives To determine safety of MBG453 given in combination with spartalizumab and SRS in patients with recurrent GBM.

Secondary Objectives

To assess the preliminary anti-tumor activity using the following measures:

  1. To estimate overall survival
  2. To estimate progression-free survival
  3. To estimate Radiographic Response (RANO and iRANO)
  4. To evaluate pain for patients undergoing the treatment of anti-TIM3 and anti-PD1 in combination with SRS

Exploratory Objectives

  1. To assess the effects of MGB453, spartalizumab and their combination with SRS on immune cells in peripheral blood, including but not limited to the T cell compartments, myeloid cells, and serum proteins (cytokines and other immune modulators).
  2. To assess the pharmacodynamic activity in tumor tissue and peripheral blood in treated subjects who undergo tumor biopsies as clinically indicated.
  3. To explore potential associations between biomarker measures and anti-tumor activity by analyzing markers of inflammation, immune activation, host tumor growth factors, and tumor-derived proteins in the pre-treatment and on-treatment setting.
  4. To explore characteristics of tumor immune microenvironment change after the treatment.

OUTLINE:

Patients receive MBG453 and spartalizumab intravenously (IV) over 30 minutes each on Day 1. Patients then undergo stereotactic radiosurgery on Day 8 per standard of care. Courses with MBG453 and spartalizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months thereafter.

Being tested
MBG453
Keywords
Immunotherapy
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MBG453Drug

    Also called spartalizumab, stereotactic radiosurgery

    Patients receive MBG453 and spartalizumab IV over 30 minutes on Day 1. Patients then undergo stereotactic radiosurgery on Day 8. Courses with MBG453 and spartalizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Study groups in NCT03961971
Study groupRoleWhat they receive
Treatment (MBG453, spartalizumab, stereotactic radiosurgery)ExperimentalPatients receive MBG453 and spartalizumab IV over 30 minutes on Day 1. Patients then undergo stereotactic radiosurgery on Day 8. Courses with MBG453 and spartalizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: MBG453

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with serious adverse events (SAE) graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 5.0

    Number of participants experiencing SAEs, as defined by NCI CTC v5.0

    Measured: Up to 12 weeks after first dose of study treatment

Secondary outcomes (4)

  1. Proportion of participants who experience grade 3 or higher toxicity, graded according to the NCI CTC v5.0

    Proportion of participants who experience grade 3 or higher toxicity, graded according to the NCI CTC v5.0

    Measured: Up to 100 days after completion of study treatment

  2. Progression-free survival

    Progression-free survival estimated using the Kaplan-Meier method. Progression as defined by Response Assessment in Neuro-oncology (RANO) criteria: Complete Response (CR)= no change in size of T1-gadolinium-enhancing (T1-Gd+) disease, stable or reduced T2/FLAIR signal, no new lesion, no corticosteroid use, and stable or improved clinical status; Partial Response (PR)= ≥50% change in size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Stable Disease (SD)= <50% reduction to <25% increase size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Progressive Disease (PD)= ≥25% increase size of T1-Gd+ disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status.

    Measured: From the date of initial diagnosis (at surgery) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

  3. Overall survival

    Overall survival as estimated using the Kaplan-Meier method.

    Measured: From the date of initial diagnosis until the date of death from any cause assessed up to 24 months

  4. Objective Response

    Proportion of participants who have objective PR or CR during the course of treatment and a measurable disease indicated in baseline scan. Progression is defined by Response Assessment in Neuro-oncology (RANO) criteria: Complete Response (CR)= no change in size of T1-gadolinium-enhancing (T1-Gd+) disease, stable or reduced T2/FLAIR signal, no new lesion, no corticosteroid use, and stable or improved clinical status; Partial Response (PR)= ≥50% change in size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Stable Disease (SD)= <50% reduction to <25% increase size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status; Progressive Disease (PD)= ≥25% increase size of T1-Gd+ disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status.

    Measured: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2019
  2. Study start18 Feb 2020
  3. Primary completion16 Nov 2022
  4. Study completion30 Jul 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03961971
Sponsor's protocol ID
J18150
Other IDs
IRB00104226
Status last verified
Oct 2026
First submitted
15 May 2019
Last updated
7 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MBG453 in people with Glioblastoma Multiforme, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with serious adverse events (SAE) graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 5.0 (time frame: Up to 12 weeks after first dose of study treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03961971.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.

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