What side effects are associated with this type of intervention?

Common treatments for glioblastoma, such as stereotactic radiosurgery (SRS) and monoclonal antibodies like MBG453 and spartalizumab, have specific side effects. SRS can lead to radiation necrosis, cerebral edema, and potential neurocognitive effects. Monoclonal antibodies may cause immune-mediated side effects including colitis, hepatitis, endocrinopathies, and skin reactions. Combining these treatments may increase the risk of these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for glioblastoma that involve radiation therapy and monoclonal antibodies. Bevacizumab, an anti-VEGF monoclonal antibody, is approved for recurrent glioblastoma and works by inhibiting blood vessel growth in tumors. Temozolomide, an oral chemotherapy drug, is often used in conjunction with radiation therapy for newly diagnosed glioblastoma. While specific combinations like stereotactic radiosurgery with MBG453 and spartalizumab are still under investigation, these existing treatments highlight the ongoing efforts to combine radiation with targeted therapies to improve outcomes in glioblastoma patients.

What other types of research exist?

Promising novel alternatives for Glioblastoma treatment in 2024 include: 1) PD-1 blockade with nivolumab, which has shown activity in recurrent atypical/anaplastic meningioma; 2) mTORC1 inhibitors like everolimus, which have been used in combination with octreotide; 3) Bevacizumab, an anti-VEGF antibody, combined with everolimus; and 4) Investigational approaches such as multitargeted kinase inhibitors (e.g., regorafenib, cabozantinib) and neurotrophic factor-secreting mesenchymal stromal cells (MSC-NTF cells).

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Monoclonal Antibodies

Anti-Tim-3 + Anti-PD-1 + SRS for Glioblastoma

Phase 1

Waitlist Available

Led By Lawrence Kleinberg, MD

Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Patients tumor target (GTV) should be ≤ 5 cm

Must not have

Prior treatment with immune-modulating therapy, other than steroids

Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the date of initial diagnosis until the date of death from any cause assessed up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial studies a combination of precise radiation therapy and immune-boosting drugs to treat patients with recurring brain cancer. The goal is to directly target the tumor and enhance the body's immune response against cancer cells.

Who is the study for?

This trial is for adults over 18 with recurrent GBM who've had first-line therapy including surgery, radiation, and Temozolomide. They must have a Karnofsky Performance Status ≥ 70, no more than two recurrences of GBM or gliosarcoma confirmed by biopsy or MRI, normal organ/marrow function, and be able to undergo MRIs. Women must not be pregnant/breastfeeding and use contraception.

What is being tested?

The trial tests the safety of stereotactic radiosurgery combined with MBG453 and spartalizumab in treating recurrent GBM. It aims to see if this combination can better target cancer cells while sparing healthy tissue compared to current treatments.

What are the potential side effects?

Potential side effects may include typical reactions from immunotherapy such as fatigue, allergic reactions to the monoclonal antibodies (MBG453 and spartalizumab), inflammation in organs due to immune response, as well as localized effects from the high-dose radiation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am not pregnant or breastfeeding and have a recent negative pregnancy test.

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My tumor is 5 cm or smaller.

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I am able to care for myself but may not be able to do active work.

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I've had surgery, radiation, and Temozolomide for my cancer, unless my tumor is MGMT unmethylated.

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I am 18 years old or older.

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I have been diagnosed with Grade IV brain cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with immune therapy, not including steroids.

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I have lung disease that causes symptoms or could affect lung-related side effect management.

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I have a known positive history of HIV or active Hepatitis B/C.

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I have had an organ or stem cell transplant.

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My cancer has spread outside of my brain.

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I've been taking more than 4 mg of dexamethasone or similar medication daily for at least 5 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the date of initial diagnosis until the date of death from any cause assessed up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the date of initial diagnosis until the date of death from any cause assessed up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the date of initial diagnosis until the date of death from any cause assessed up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

Objective Response

Overall survival

Progression-free survival

+1 more

Side effects data

From 2024 Phase 2 trial • 127 Patients • NCT03946670

47%

Constipation

42%

Diarrhoea

37%

Neutropenia

32%

Anaemia

29%

Thrombocytopenia

24%

Nausea

24%

Pyrexia

24%

Febrile neutropenia

23%

Fatigue

21%

White blood cell count decreased

21%

Decreased appetite

19%

Neutrophil count decreased

19%

Platelet count decreased

19%

Rash

18%

Pain in extremity

18%

Hypokalaemia

18%

Dyspnoea

16%

Back pain

16%

Pruritus

15%

Asthenia

15%

Weight decreased

13%

Dizziness

13%

Insomnia

13%

Headache

13%

Oedema peripheral

13%

Urinary tract infection

13%

Pneumonia

13%

Cough

13%

Epistaxis

11%

Arthralgia

11%

Hypertension

10%

Haemorrhoids

10%

COVID-19

10%

Myalgia

10%

Contusion

10%

Vomiting

10%

Aspartate aminotransferase increased

10%

Hypoalbuminaemia

10%

Erythema

10%

Night sweats

Acute kidney injury

Atrial fibrillation

Abdominal pain

SARS-CoV-2 test negative

Oropharyngeal pain

Paraesthesia

Hyponatraemia

Dysuria

Stomatitis

Procedural pain

Herpes zoster

Alanine aminotransferase increased

Injection site reaction

Blood alkaline phosphatase increased

Hyperglycaemia

Hyperuricaemia

Haematuria

Haematoma

Pain

Sepsis

Blood lactate dehydrogenase increased

Lymphocyte count decreased

Respiratory tract infection

Oedema

Cellulitis

Transfusion reaction

Oral herpes

Septic shock

Injection site erythema

Blood creatinine increased

Gamma-glutamyltransferase increased

Hyperkalaemia

Hypernatraemia

Purpura

Hypotension

General physical condition abnormal

Haemoglobin decreased

Pseudomonal bacteraemia

Pneumonitis

Hypomagnesaemia

Peripheral sensory neuropathy

Lung disorder

Pleural effusion

Squamous cell carcinoma of the hypopharynx

Escherichia bacteraemia

Gastrointestinal bacterial infection

Anal haemorrhage

Bronchopulmonary aspergillosis

Cardiac arrest

Abdominal pain upper

Dermo-hypodermitis

Pancreatitis acute

Pathological fracture

Lip squamous cell carcinoma

Metastases to bone

Cerebral haemorrhage

Conjunctival haemorrhage

Peripheral artery stenosis

Chest pain

Blood bilirubin increased

Hyperleukocytosis

Staphylococcal infection

Urosepsis

Fall

Febrile nonhaemolytic transfusion reaction

Infusion related reaction

100%

80%

60%

40%

20%

Study treatment Arm

MBG453 + Hypomethylating Agents

Placebo + Hypomethylating Agents

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (MBG453, spartalizumab, stereotactic radiosurgery)Experimental Treatment1 Intervention

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MBG453

2017

Completed Phase 2

~410

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Glioblastoma treatments often involve stereotactic radiosurgery (SRS) and monoclonal antibodies. SRS delivers high doses of radiation directly to the tumor, minimizing damage to surrounding healthy tissue, which is crucial for controlling tumor growth. Monoclonal antibodies like MBG453 and spartalizumab target immune checkpoint proteins TIM-3 and PD-1, respectively, enhancing the body's immune response against the tumor. This combination aims to maximize tumor control and improve patient outcomes by leveraging both direct tumor targeting and immune system activation.

Advances in the biology of astrocytomas.