What side effects are associated with this type of intervention?

Common side effects of PD-1 inhibitors like pembrolizumab include fatigue, rash, diarrhea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Immune system stimulation therapies, such as the ATL-DC vaccine, may cause injection site reactions, flu-like symptoms, and other immune-related effects. Combining these treatments may increase the risk of immune-related adverse events, requiring careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, including temozolomide, an oral chemotherapy drug, and bevacizumab, an anti-angiogenic therapy. Immunotherapy approaches, such as the use of PD-1 inhibitors like Pembrolizumab, are being actively studied, but as of now, there are no FDA-approved PD-1 inhibitors specifically for Glioblastoma. Vaccine-based therapies, like the ATL-DC vaccine, are also under investigation, aiming to stimulate the immune system to target tumor cells more effectively. These innovative approaches are part of ongoing clinical trials to improve outcomes for patients with recurrent Glioblastoma.

What other types of research exist?

Promising novel alternatives for Glioblastoma treatment in 2024 include: 1) Combination therapies involving immune checkpoint inhibitors like nivolumab and ipilimumab, which have shown activity in other cancers and are being explored for GBM. 2) Experimental approaches such as chimeric antigen receptor (CAR)-T cell therapies, which are being tested in various cancers including prostate cancer and may have potential in GBM. 3) Investigational drugs targeting specific pathways or mutations in GBM, which are under clinical evaluation. Further research and clinical trials are needed to validate the efficacy of these alternatives.

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Cancer Vaccine

Pembrolizumab + Vaccine for Glioblastoma

Phase 1

Recruiting

Led By Timothy F Cloughesy

Research Sponsored by Jonsson Comprehensive Cancer Center

Eligibility Criteria Checklist

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

Must have

Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (collected within 14 days prior to the start of study treatment) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])

Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks

Must not have

Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug

Has known tumor primarily localized to the brainstem or spinal cord

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years

Summary

This trial is testing a combination of an immunotherapy drug, pembrolizumab, and a vaccine, ATL-DC, in patients with recurrent glioblastoma that can be surgically removed. The goal is to see if this combination can help the immune system better attack the cancer and improve patient outcomes.

Who is the study for?

This trial is for adults with recurrent glioblastoma that can be surgically removed. They must have a tumor of a certain size, not be on immunosuppressive therapy, and agree to use contraception. Excluded are pregnant or breastfeeding women, those with recent other cancer treatments or live vaccines, severe allergies to pembrolizumab, active infections like HIV or hepatitis B/C, and autoimmune diseases treated within the last 2 years.

What is being tested?

The trial tests how well pembrolizumab (an antibody) works alongside an ATL-DC vaccine in treating recurrent glioblastoma compared to the vaccine alone. The study aims to see if this combination helps the immune system better attack cancer cells and prevent their growth.

What are the potential side effects?

Possible side effects include reactions at the injection site from the vaccine and typical immune-related adverse effects from pembrolizumab such as fatigue, skin issues, inflammation of organs like lungs or intestines (pneumonitis/colitis), hormonal imbalances due to thyroid gland problems.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function, measured by creatinine or GFR, is within the required range.

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I haven't had a blood transfusion or taken erythropoietin in the last 2 weeks.

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It has been at least 28 days since my last surgery.

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I can provide a tissue sample from my brain tumor 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 glioblastoma has returned or worsened and can be operated on.

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My tumor is at least 2cm by 2cm in size, confirmed by MRI.

Exclusion Criteria

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

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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My tumor is mainly in my brainstem or spinal cord.

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I have an active tuberculosis infection.

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

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I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

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I have another cancer that is getting worse or was treated in the last 3 years.

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I have a history of hepatitis B or active hepatitis C.

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I have had or currently have lung inflammation treated with steroids.

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I have been treated with specific immune therapy targeting cancer.

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I am currently being treated for an infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Expansion of T cell receptor (TCR) clones

Incidence of adverse events (AEs)

Secondary study objectives

6 month progression-free survival (PFS6)

Overall survival (OS)

Other study objectives

Biomarker analysis

T cell subset and activation markers within peripheral blood measured by flow cytometry

TIL (tumor infiltrating lymphocyte) density and TCR (T cell receptor) Clonality in the tumor quantitatively measured by next generation TCR sequencing

+4 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Group A (pembrolizumab, ATL-DC, poly ICLC)Experimental Treatment3 Interventions

Beginning 14 days prior to scheduled surgery, patients receive pembrolizumab IV over 30 minutes. After surgery, patients receive pembrolizumab IV over 30 minutes on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

Group II: Group B (placebo, ATL-DC, poly ICLC)Active Control3 Interventions

Beginning 14 days prior to scheduled surgery, patients receive placebo IV. After surgery, patients receive placebo IV on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3130

Poly ICLC

2014

Completed Phase 2

~270

0 / 17Eligibility 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

Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway that tumors use to evade the immune system, thereby enhancing the immune system's ability to recognize and attack cancer cells. The ATL-DC vaccine stimulates the immune system by presenting tumor antigens to immune cells, boosting the body's ability to target and destroy glioblastoma cells. These treatments are significant for Glioblastoma patients as they leverage the body's immune system for a more targeted and potentially effective approach to combating the cancer.