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Checkpoint Inhibitor

Nivolumab + Ipilimumab with Surgery for Glioblastoma

Phase 1

Waitlist Available

Led By Patrick Y Wen, MD

Research Sponsored by Patrick Wen, MD

Eligibility Criteria Checklist

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

Must have

Age ≥ 18 years on day of signing informed consent

Unequivocal evidence for tumor progression by MRI per RANO criteria

Must not have

Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody

Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of registration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Summary

This trial is studying the safety and effectiveness of nivolumab in combination with ipilimumab and surgery when used in the treatment of recurrent glioblastoma.

Who is the study for?

Adults (18+) with Grade IV IDH wildtype glioblastoma at first or second relapse, who are undergoing clinically indicated surgery. Participants must have a Karnofsky performance status ≥ 70, sufficient tissue from prior surgery for analysis, and no active infections or additional malignancies. They should not have received certain treatments like bevacizumab or systemic immunosuppressives recently and must agree to use effective contraception.

What is being tested?

The trial is testing the safety and effectiveness of nivolumab combined with ipilimumab alongside surgery in treating recurrent glioblastoma. A placebo group is included for comparison. An optional sub-study involves Zr-89 Crefmirlimab berdoxam.

What are the potential side effects?

Potential side effects include immune-related reactions that can affect organs, infusion reactions similar to allergic responses, fatigue, increased risk of infections due to weakened immunity, and possibly other unforeseen complications related to the drugs' actions on the immune system.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My MRI shows my tumor is growing.

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I have received radiotherapy as my first treatment.

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My MRI shows my tumor is growing.

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My cancer has returned once or twice after initial treatment.

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My brain tumor is a Grade IV glioblastoma without IDH mutation.

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I can provide a tissue sample from my tumor for testing.

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I have waited the required time after my last cancer treatment before joining this trial.

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My brain tumor is a type of aggressive cancer known as glioblastoma.

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I have recovered from major side effects of my previous treatments.

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I have enough tissue from a previous surgery for testing.

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

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My condition has worsened for the first or second time after improving.

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I have received radiotherapy as my first treatment.

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 specific immune therapy drugs before.

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I haven't had severe bleeding in the last 6 months.

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I have another cancer that is getting worse or needs treatment.

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I have had specific local treatments like brachytherapy or stereotactic surgery.

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I am currently being treated for an infection.

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I have not received a live vaccine in the last 30 days.

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My cancer has an IDH mutation.

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I have an active tuberculosis infection.

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I have been diagnosed with an immune system disorder.

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I need high dose steroids (more than 2 mg/day of dexamethasone or equivalent) for at least 3 days.

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My cancer has spread to the lining of my brain or other parts of my body.

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I have not taken immunosuppressive drugs, except steroids, in the last 6 months.

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I have been treated for an autoimmune disease in the last 2 years.

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My tumor is mainly in my brainstem or spinal cord.

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I have received treatments like bevacizumab or aflibercept.

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I have a history of or currently have non-infectious lung inflammation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

Pharmacotherapy

Tumor Infiltrating T Lymphocyte (TIL) Density

Secondary study objectives

Cell Cycle-Related Genetic Signature within the Tumor Microenvironment

Percentage of Progression Free Survival (PFS-6)

Side effects data

From 2023 Phase 3 trial • 521 Patients • NCT04109066

65%

Alopecia

48%

Nausea

36%

Anaemia

26%

Fatigue

25%

Aspartate aminotransferase increased

24%

Diarrhoea

21%

Alanine aminotransferase increased

20%

Asthenia

20%

Vomiting

19%

Neutropenia

19%

Headache

19%

Neuropathy peripheral

17%

Constipation

16%

Neutrophil count decreased

16%

COVID-19

15%

Arthralgia

14%

Rash

13%

Decreased appetite

13%

Hypothyroidism

12%

White blood cell count decreased

12%

Hyperglycaemia

12%

Radiation skin injury

11%

Myalgia

11%

Lymphopenia

Epistaxis

Urinary tract infection

Hypertension

Cough

Infusion related reaction

Pyrexia

Pruritus

Blood alkaline phosphatase increased

Dysgeusia

Dizziness

Dyspepsia

Hot flush

Hypersensitivity

Paraesthesia

Abdominal pain upper

Mucosal inflammation

Illness

Peripheral sensory neuropathy

Back pain

Insomnia

Hyperthyroidism

Pain in extremity

Leukopenia

Blood lactate dehydrogenase increased

Anxiety

Weight decreased

Folliculitis

Oedema peripheral

Blood thyroid stimulating hormone increased

Pain

Dry mouth

Adrenal insufficiency

Abdominal pain

Hyponatraemia

Dyspnoea

Nasopharyngitis

Hypokalaemia

Dry eye

Lacrimation increased

Gastrooesophageal reflux disease

Blood thyroid stimulating hormone decreased

Stomatitis

Lymphocyte count decreased

Palpitations

Depression

Onycholysis

Pulmonary embolism

Breast pain

COVID-19 pneumonia

Dry skin

Procedural pain

Tachycardia

Oropharyngeal pain

Febrile neutropenia

Bone pain

Postoperative wound infection

Thrombocytopenia

Malignant neoplasm progression

Rash maculo-papular

Nail disorder

Cervix carcinoma

Vertigo

Cardio-respiratory arrest

Thyroiditis subacute

Arterial thrombosis

Embolism

Interstitial lung disease

Myelosuppression

Diabetic ketoacidosis

Cardiac failure

Immune-mediated adrenal insufficiency

Myocardial infarction

Chills

Colitis

Upper respiratory tract infection

Infection

Glomerulonephritis

Cardiac perfusion defect

Hypotension

Hepatitis cholestatic

Myocarditis

Pneumonia bacterial

Left ventricular failure

Anaphylactic reaction

Pneumonia

Intracranial pressure increased

Pemphigoid

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Nivo + Chemo (PTX QW + AC Q3W) / Nivo + ET

Arm A: Nivo + Chemo (PTX QW + AC Q2W) / Nivo + ET

Arm B: Nivo Placebo + Chemo (PTX QW + AC Q3W) / ET

Arm B: Nivo Placebo + Chemo (PTX QW + AC Q2W) / ET

Trial Design

3Treatment groups

Experimental Treatment

Group I: Placebo-Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab and Ipilimumab After SurgeryExperimental Treatment5 Interventions

One dose of placebo-nivolumab plus placebo-ipilimumab will be administered 14(±5) days before surgery. After surgery, participants receive nivolumab in combination with ipilimumab every 3 weeks for 9 weeks and then nivolumab alone every 4 weeks

Group II: Nivolumab and Placebo-Ipilimumab Before Surgery, Nivolumab After SurgeryExperimental Treatment3 Interventions

One dose of nivolumab plus placebo-ipilimumab will be administered 14(±5) days before surgery. After surgery, participants receive nivolumab in combination with ipilimumab every 3 weeks for 9 weeks and then nivolumab alone every 4 weeks.

Group III: Nivolumab and Ipilimumab Before and After SurgeryExperimental Treatment3 Interventions

One dose of nivolumab plus ipilimumab will be administered 14(±5) days before surgery. After surgery, participants receive nivolumab in combination with ipilimumab every 3 weeks for 9 weeks and then nivolumab alone every 4 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2015

Completed Phase 3

~4010

Ipilimumab

2015

Completed Phase 3

~3070