Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Jonsson Comprehensive Cancer Center
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Is the treatment Pembrolizumab + Vaccine a promising treatment for Glioblastoma?Yes, Pembrolizumab combined with a vaccine is promising for treating Glioblastoma. Pembrolizumab, an immunotherapy drug, has shown antitumor activity in glioblastoma patients. Vaccines like ATL-DC can potentially improve survival rates by boosting the immune system to fight the cancer.467810
What safety data exists for the treatment of Pembrolizumab and ATL-DC Vaccine in glioblastoma?The safety of pembrolizumab (also known as KEYTRUDA or MK-3475) has been evaluated in the KEYNOTE-028 trial, which reported on its use in PD-L1-positive recurrent glioblastoma. The trial focused on the antitumor activity and safety of pembrolizumab. Additionally, dendritic cell (DC) vaccines, similar to the ATL-DC Vaccine, have been shown to be safe and non-toxic in phase I or I-II trials for glioblastoma. These studies demonstrated that DC vaccination is safe and may increase overall survival. The AV-GBM-1 vaccine, another DC-based approach, was assessed for safety in a phase II trial, which included monitoring for adverse events. Overall, both pembrolizumab and DC vaccines have been evaluated for safety in clinical trials, showing promising results in terms of safety and potential efficacy.158910
What data supports the idea that Pembrolizumab + Vaccine for Glioblastoma is an effective treatment?The available research shows that dendritic cell vaccines, like the ATL-DC vaccine, are promising for treating glioblastoma. They have been shown to increase patient survival and have mild side effects. In one study, patients who received a similar vaccine had improved survival rates compared to those who did not. Additionally, the ATL-DC vaccine allows for wider patient eligibility compared to other similar treatments, which means more patients can potentially benefit from it. These findings suggest that the Pembrolizumab + Vaccine combination could be an effective treatment for glioblastoma.234510
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you must not be on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study drug. It's best to discuss your current medications with the trial team.
Eligibility Criteria
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.Inclusion Criteria
My kidney function, measured by creatinine or GFR, is within the required range.
I haven't had a blood transfusion or taken erythropoietin in the last 2 weeks.
It has been at least 28 days since my last surgery.
I can provide a tissue sample from my brain tumor for testing.
I am able to care for myself but may not be able to do active work.
My glioblastoma has returned or worsened and can be operated on.
My tumor is at least 2cm by 2cm in size, confirmed by MRI.
Exclusion Criteria
I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.
My tumor is mainly in my brainstem or spinal cord.
I have an active tuberculosis infection.
I have not received a live vaccine in the last 30 days.
I haven't needed systemic treatment for an autoimmune disease in the last 2 years.
I have another cancer that is getting worse or was treated in the last 3 years.
I have a history of hepatitis B or active hepatitis C.
I have had or currently have lung inflammation treated with steroids.
I have been treated with specific immune therapy targeting cancer.
I am currently being treated for an infection.
Treatment Details
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.
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.
Find a clinic near you
Research locations nearbySelect from list below to view details:
QuanLos Angeles, CA
UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, CA
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Who is running the clinical trial?
Jonsson Comprehensive Cancer CenterLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
Phase One FoundationCollaborator
National Cancer Institute (NCI)Collaborator
Oncovir, Inc.Industry Sponsor
References
Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice. [2006]In recent years, the use of dendritic cells (DC), the most powerful antigen presenting cells, has been proposed for the creation of vaccines against gliomas. This approach has been demonstrated to be safe and non-toxic in phase I or I-II trials (2, 3). Immunotherapy plays a central role in the search for new treatments for glioblastoma multiforme (GBM). In particular, several phase I studies have been performed using DC pulsed by GBM proteins as a vaccine for patients with relapsing GBM. The studies demonstrated that DC vaccination is safe and may produce a significant increase in overall survival. As the first step in the preparation of appropriate conditions for a clinical evaluation in Italy, we have performed pre-clinical experiments on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally with DC loaded with a GL261 homogenate. These results show that vaccination with DC pulsed with a tumor lysate increases considerably survival in mice bearing intracranial glioblastomas and supports the development of DC-based clinical trials for patients with glioblastomas that do not respond to standard therapies.
Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients. [2021]Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA.
Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. [2021]Dendritic cell (DC) vaccination is emerging as a promising therapeutic option for malignant glioma patients. However, the optimal antigen formulation for loading these cells has yet to be established. The objective of this study was to compare the safety, feasibility, and immune responses of malignant glioma patients on 2 different DC vaccination protocols. Twenty-eight patients were treated with autologous tumor lysate (ATL)-pulsed DC vaccination, whereas 6 patients were treated with glioma-associated antigen (GAA) peptide-pulsed DCs. Safety, toxicity, feasibility, and correlative immune monitoring assay results were compared between patients on each trial. Because of HLA subtype restrictions on the GAA-DC trial, 6/15 screened patients were eligible for treatment, whereas 28/32 patients passed eligibility screening for the ATL-DC trial. Elevated frequencies of activated natural killer cells were observed in the peripheral blood from GAA-DC patients compared with the ATL-DC patients. In addition, a significant correlation was observed between decreased regulatory T lymphocyte (Treg) ratios (postvaccination/prevaccination) and overall survival (P = 0.004) in patients on both trials. In fact, Treg ratios were independently prognostic for overall survival in these patients, whereas tumor pathology was not in multivariate analyses. In conclusion, these results suggest that ATL-DC vaccination is associated with wider patient eligibility compared with GAA-DC vaccination. Decreased postvaccination/prevaccination Treg ratios and decreased frequencies of activated natural killer cells were associated with prolonged survival in patients from both trials, suggesting that these lymphocyte subsets may be relevant immune monitoring endpoints for immunotherapy protocols in malignant glioma patients.
DCVax®-L--developed by Northwest Biotherapeutics. [2018]Dendritic cell (DC) immunotherapy is emerging as a potential addition to the standard of care in the treatment of glioblastoma multiforme (GBM). In the last decade or so various research groups have conducted phase I and II trials of DC-immunotherapy on patients with newly diagnosed (ND) and recurrent GBM and other high-grade gliomas in an attempt to improve the poor prognosis. Results show an increase in overall survival (OS), while vaccination-related side effects are invariably mild. Northwest Biotherapeutics, Inc., Bethesda, Maryland, U.S.A. (NWBT) developed the DCVax®-L vaccine as an adjunct to the treatment of GBM. It is currently under evaluation in a phase III trial in patients with ND-GBM, which is the only ongoing trial of its kind. In this review current data and perspectives of this product are examined.
Advances and challenges: dendritic cell vaccination strategies for glioblastoma. [2021]Glioblastoma is the most common primary brain tumor in adults and prognosis remains poor with a median survival of approximately 15-17 months. This review provides an overview of recent advances in the field of glioblastoma immunotherapy. Areas covered: Recent advances in dendritic cell vaccination immunotherapy are showing encouraging results in clinical trials and promise to extend patient survival. In this report we discuss current scientific knowledge regarding dendritic cell (DC) vaccines, including approaches to differentiating, priming, and injecting dendritic cells to achieve maximal anti-tumor efficacy in glioblastoma. These findings are compared to recently completed and currently ongoing glioblastoma clinical trials. Novel methods such as 'fastDCs' and vaccines targeting DCs in-vivo may offer more effective treatment when compared to traditional DC vaccines and have already entered the clinic. Expert commentary: Finally, we discuss the challenges of T-cell dysfunctions caused by glioblastoma immunosuppression and how they affect dendritic cell vaccinations approaches.
Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. [2021]We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.
Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. [2022]VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma.
Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. [2021]Current treatments for recurrent glioblastoma offer limited benefit. The authors report the antitumor activity and safety of the anti-programmed death 1 (anti-PD-1) immunotherapy, pembrolizumab, in programmed death ligand 1 (PD-L1)-positive, recurrent glioblastoma.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment. [2023]Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) Adverse Events (AE) associated with AV-GBM-1 administration, and (3) survival.