ERC1671 to Treat Malignant Gliomas When Given in Combination With GM-CSF, Cyclophosphamide, Bevacizumab and Pembrolizumab

NCT05366062 | Not Yet Recruiting Phase 2

• 1 other identifier: ERC1671PEM
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a treatment clinical trial to assess the efficacy of ERC1671 in combination with bevacizumab and pembrolizumab in patients with GBM that has progressed following treatment with radiation and temozolomide. Patients will have surgery to collect the maximum amount of GBM tissue that can be reasonably collected. This tissue will be used to manufacturer ERC1671 for the patient. The patients will receive ERC1671 in combination with GM-CSF and cyclophosphamide, in combination with bevacizumab and pembrolizumab.

Conditions

Glioma, Malignant

Keywords

ERC1671; GM-CSF; Cyclophosphamide; Bevacizumab; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Overall Survival at 12 months

  Overall Survival at 12 months as assessed per iRANO Criteria.

  12 months

Secondary Outcomes (3)

• Progression-free survival

  12 Months

• Radiographic Response

  12 Months

• Number of participants with Adverse Events [Safety and Tolerability]

  12 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

This is a Treatment Protocol for patients with severe and immediately life-threatening GBM that had surgical resection and first line treatment with radiation therapy and temozolamide per current standard of care. Patients will be treated with recurring 28-day cycles of ERC1671, GM-CSF, Cyclophosphomide, Bevacizumab, and Pembrolizumab until progression of disease and at the discretion of the treating physician.

Drug: ERC1671; Drug: GM-CSF; Drug: Cyclophosphamide; Drug: Pembrolizumab

Interventions

ERC1671 DRUG

ERC1671 is an autologous and allogeneic cells and lysates suspension generated from human glioblastoma (GBM) tumors harvested from patients undergoing surgery for glioblastoma. For each patient the treatment is composed of three allogeneic cells vaccine and lysates vaccine (ERC1671 A, B, C) plus from one autologous cells and lysate (ERC1671D).

Treatment Arm

GM-CSF DRUG

Sargramostim (Leukomax®, Leukine®); yeast-derived, recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF)

Treatment Arm

Cyclophosphamide DRUG

Cyclophosphamide is an alkylating agent, used for immunopotentiation. This drug is FDA approved and is being used off-label for the condition of hematopoietic stem cell transplant conditioning as an antineoplastic and immunosuppressant agent to modulate immunity.

Treatment Arm

Pembrolizumab DRUG

A therapeutic antibody that binds to and blocks PD-1 located on lymphocytes. The receptor is generally responsible for preventing the immune system from attacking the body's own tissues - it is an immune checkpoint inhibitor.

Also known as: Keytruda

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years of age.
• KPS of ≥ 60%.
• Life expectancy \> 12 weeks.
• First, second, third or fourth relapse of glioblastoma.
• Previous treatment for glioblastoma must include surgery (biopsy, partial resection, or full surgical resection), conventional radiation therapy and temozolomide (TMZ).
• MRI record must be obtained showing the MRI was done at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy, or at least 4 weeks after radiation for a new lesion outside the prior primary radiation field unless relapse is confirmed by tumor biopsy or new lesion outside of radiation field, or if there are two MRIs confirming progressive disease that are 8 weeks apart.
• If prior therapy with gamma knife or other focal high-dose radiation, must have subsequent histologic documentation of local relapse, or relapse with new lesion outside the irradiated field.
• Resolution of all chemotherapy or radiation-related toxicities ≤ CTCAE Grade severity, except for alopecia and hematologic toxicity. Patients taking temozolomide can start study treatment 23 days from the last temozolomide dose. For all other chemotherapy drugs, study treatment can start as long as all adverse events related to their prior treatment are no higher than Grade 1.
• Systemic corticosteroid therapy must be at a dose of ≤ 4 mg of dexamethasone or equivalent per day during the week prior to Day 1.
• Bi-dimensionally measurable disease (as per iRANO criteria).
• Patients must have normal organ and marrow function as defined below:
• Hemoglobin (Hbg) \> 9g/dL,
• Leukocytes \>1,500/mcL
• Absolute neutrophil count\>1,000/mcL
• CD4 count \> 300/mcl

You may not qualify if:

• Subjects unable to undergo an MRI with contrast
• Subjects able and willing to participate in an open and accruing ERC clinical trial
• Presence of diffuse leptomeningeal disease
• History, presence, or suspicion of metastatic disease
• Administration of immunosuppressive drugs less than 2 weeks prior to first dose of ERC1671 except dexamethasone for cerebral edema as detailed above;
• Known contraindication or hypersensitivity to any component of bevacizumab.
• Evidence of recent hemorrhage on screening MRI of the brain with the following exceptions: presence of hemosiderin; resolving hemorrhagic changes related to surgery; presence of punctate hemorrhage in the tumor.
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1.
• Evidence of bleeding diathesis or coagulopathy as documented by an elevated PT, PTT or bleeding time and clinically significant;
• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 1.
• Urine protein: creatinine ratio 1.0 at screening;
• Anticipation of need for major surgical procedure during the course of the study.
• Serious non-healing wound, ulcer, or bone fracture.
• Active infection requiring treatment, known immunosuppressive disease, active systemic autoimmune diseases such as lupus, receipt of systemic immunosuppressive therapy, human immunodeficiency virus (HIV) infection, Hepatitis B or Hepatitis C.
• Uncontrolled hypertension, blood pressure of \> 150 mmHg systolic and \> 100 mmHg diastolic, or history of hypertensive encephalopathy. Subjects with any known uncontrolled inter-current illness including ongoing or active infection, symptomatic congestive heart failure (NYHA Gr.2 or \>), myocardial infarction, unstable angina pectoris within the past 12 months

Sponsors & Collaborators

• Epitopoietic Research Corporation: lead

Study Sites (1)

Bumrungrad International Hospital

Bangkok, Vadhana, 10110, Thailand

Location

Related Publications (14)

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  PMID: 2827051 RESULT

MeSH Terms

Conditions

Glioma

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Cyclophosphamide; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Joseph Elliott, PhD

CONTACT

+1-416-721-5116; jelliot@erc-usa.com

Christopher Beardmore

CONTACT

3104808973; chris@anovaevidence.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 9, 2022
• Study Start: July 1, 2022
• Primary Completion: July 31, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: May 13, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)