Pembrolizumab + M032 for Glioblastoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: University of Alabama at Birmingham
Must not be taking: Anti-PD-1, Anti-PD-L1, Anti-PDL2, HSV drugs
Disqualifiers: Pregnancy, Immunodeficiency, Active infection, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This Phase I (Cohort I and Cohort II) and Phase II trial is designed to confirm the safety and tolerability of Pembrolizumab when given in conjunction with M032, an Oncolytic Herpes Simplex Virus (oHSV) that expresses IL-12 and perform the Phase II portion using a Recommended Phase 2 Dose (RP2D) of M032 (provided by the Phase I) when given in conjunction with Pembrolizumab for recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or glio-sarcoma).
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain therapies like chronic systemic steroids or drugs active against HSV. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Pembrolizumab + M032 for treating glioblastoma?
Research shows that pembrolizumab, a part of this treatment, has shown antitumor activity in recurrent glioblastoma, especially in cases where the tumor is PD-L1 positive. Additionally, pembrolizumab has been effective in treating melanoma by helping the immune system attack cancer cells.
12345Is the combination of Pembrolizumab and M032 generally safe for humans?
Pembrolizumab, also known as Keytruda, is generally considered safe but can cause immune-related side effects, such as type 1 diabetes in rare cases (0.2% of patients). Safety data specific to the combination with M032 is not available, but Pembrolizumab has been studied in various cancers, showing a manageable safety profile.
12678How is the treatment with Pembrolizumab + M032 for glioblastoma different from other treatments?
This treatment combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with M032, a modified virus designed to deliver a gene that boosts immune response, offering a novel approach by potentially enhancing the immune system's ability to target glioblastoma.
12345Eligibility Criteria
Adults over 18 with specific brain cancers (glioblastoma, astrocytoma, gliosarcoma) who've had prior treatments fail. They must be able to undergo tumor resection, have a life expectancy over 4 weeks, and agree to contraception use. Excluded are those with recent adverse event recovery issues, HSV drug therapy, certain allergies or infections, other active cancers within 3 years, or uncontrolled illnesses.Inclusion Criteria
I have an MRI indicating a likely malignant brain tumor, with no prior glioma diagnosis or surgery except for a diagnostic biopsy.
I have a type of brain tumor that might be operable again.
I have a specific type of brain tumor and am considered a candidate for surgery to remove it.
+14 more
Exclusion Criteria
I have been treated with specific immune therapy targeting cancer.
I have a history of encephalitis, multiple sclerosis, or another CNS infection.
I have not received a live vaccine in the last 30 days.
+28 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Surgical and Initial Treatment
Patients undergo craniotomy and resection, followed by initial administration of M032 directly into the tumor bed.
1 week
1 visit (in-person)
Treatment
Patients receive combined Pembrolizumab and M032 treatments every three weeks for up to three cycles.
9 weeks
3 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with assessments including MRI and neurologic evaluation.
6 months
Extension
Patients who are responding to treatment may be considered for additional dosing after the trial period has been completed.
Up to 1 year
Participant Groups
The trial is testing the safety and effectiveness of Pembrolizumab combined with M032 (an oncolytic virus expressing IL-12) in patients with recurrent malignant gliomas. It's structured in phases to determine the best dose of M032 before assessing its efficacy alongside Pembrolizumab.
2Treatment groups
Experimental Treatment
Group I: Recurrent MGExperimental Treatment2 Interventions
To determine the safety and tolerability of M032 at the doses examined when given in combinations with pembrolizumab in patients with recurrent MG.
Group II: Newly Diagnosed MGExperimental Treatment2 Interventions
To determine Overall Survival at 12 and 24 months, and Progression Free Survival at 6 months (PFS-6) in patients with newly diagnosed glioblastoma multiforme of M032 when given in combinations with pembrolizumab (while maintaining safety).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Alabama at BirminghamBirmingham, AL
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Who Is Running the Clinical Trial?
University of Alabama at BirminghamLead Sponsor
References
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.
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy. [2022]We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy.
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.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
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.