Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma

A Phase 3 Randomized Double-blind, Controlled Study of ICT-107 With Maintenance Temozolomide (TMZ) in Newly Diagnosed Glioblastoma Following Resection and Concomitant TMZ Chemoradiotherapy

ICT-107 consists of dendritic cells, prepared from autologous mononuclear cells that are pulsed with six synthetic peptides that were derived from tumor associated antigens (TAA) present on glioblastoma tumor cells. This is a Phase 3 study to evaluate ICT-107 in patients with newly diagnosed glioblastoma. Subjects will be randomized to receive standard of care chemoradiation (temozolomide (TMZ) with either ICT-107 or a blinded control. Reinfusion with the pulsed dendritic cells should stimulate cytotoxic T cells to specifically target glioblastoma tumour cells.

Study Overview

• Status: Suspended
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Biological: ICT-107; Biological: Placebo

Detailed Description

This is a double blind Phase III study where eligible subjects are randomized into two treatment arms following the SOC primary treatment with chemoradiation: Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ), Arm 2 will receive TMZ with a blinded control. A 1:1 randomization will be employed, where ARM 1 will receive ICT-107 and Arm 2 will receive placebo control. All subjects must be HLA-A2+. All subjects must have glioblastoma tissue that has tumor assessment for MGMT methylation status prior to randomization (for stratification). Subjects will have had tumor resection and magnetic resonance imaging (MRI) prior to enrollment into the study. After signing of written informed consent and any required privacy compliance forms and screening, enrolled subjects will undergo large volume apheresis at the study site for collection of PBMCs. Apheresis product will be sent to the manufacturing site where both active therapy (ICT-107) and control will be prepared for each subject prior to randomization The study period consists of 4 time periods; a 6-week Post-Surgery Standard of Care Treatment Phase where subjects receive radiotherapy and TMZ; TMZ and radiation to be initiated no more than 8 weeks after surgical resection of glioblastoma; a Rest Period of no more than 14 days where subjects are reassessed for eligibility, and then randomized; a 4 week Induction Phase where study therapy (ICT-107 or Control) is given weekly; followed by a Maintenance Phase where study therapy is given monthly for 11 months, and then every 6 months until either progression, withdrawal from the study, death, or the supply of autologous study therapy is exhausted. Randomized subjects will receive 4 weekly administrations of subject-specific study therapy (ICT-107 or Control) during the Induction Phase. No TMZ will be given during the 4 week Induction Phase. Each study therapy injection will be delivered intradermally (axilla).

The Maintenance Phase will consist of administration of subject-specific study therapy monthly for 11 months after the Induction Phase (for a total of 15 injections over 12 months during the Induction and Maintenance Phases), and then every 6 mos. thereafter until depletion or confirmation of progressive disease (PD). During the Maintenance Phase (where ICT-107 or control are given monthly), the administration of TMZ and subject specific study therapy or control will be separated in time by approximately 2 weeks (see Section 9.1.4). Pre-treatment, treatment and assessment schedules will be the same for all subjects.

• Study Type: Interventional
• Enrollment (Estimated): 234
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medical University Innsbruck, Dept. of Neurology
  • Linz, Austria, 4020
    • Kepler Universitätsklinikum, Neuromed Campus
  • Salzburg, Austria, 5020
    • University Clinic for Neurology
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A2B4
      • Montreal Neurological Institute & Hospital
    • Sherbrooke, Quebec, Canada, J1K2R1
      • CHUS Service de Neurochirurgie
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Dignity Health - St. Joseph's Hospital and Medical Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope Cancer Center
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90027
      • Southern California Permanente Medical Group
    • Orange, California, United States, 92868
      • University of California Irvine Chao Family Cancer Center
    • Redwood City, California, United States, 94063
      • Kaiser Permanente
    • Sacramento, California, United States, 95825
      • Kaiser Permanente
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
    • Stanford, California, United States, 95124
      • Stanford Cancer Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern Connecticut
    • New Haven, Connecticut, United States, 06519
      • Smilow Cancer Hospital
  • Delaware
    • Newark, Delaware, United States, 19711
      • Christiana Care Health Services
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital Lynn Cancer Institute
    • Boca Raton, Florida, United States, 33484
      • Delray Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Harvard Medical School Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • John Nasseff Neuroscience Institute
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro-Minnesota Community Oncology Research Consortium
  • New Jersey
    • Edison, New Jersey, United States, 08820
      • JFK New Jersey Neuroscience Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • New Mexico Cancer Care Alliance
  • New York
    • Lake Success, New York, United States, 11042
      • North Shore University Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10065
      • Weil Cornell Medical Center
    • New York, New York, United States, 10016
      • Perlmutter Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center Cancer Pavilion
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Cancer Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor Health Charles Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center Memorial Hermann Hospital
    • San Antonio, Texas, United States, 78229
      • CTRC at UTHSCSA
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98122
      • Ivy Center for Advanced Brain Tumor Treatment Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects must understand and sign the study specific informed consent
2. Subjects must be in primary remission
3. Subjects should have < 1 cm3 disease by MRI within the previous 4 weeks (by central read)
4. Subjects must be HLA-A2 positive by central lab

5. Subjects must have adequate renal, hepatic and bone marrow function based on screening laboratory assessments. Baseline hematologic studies and chemistry and coagulation profiles must meet the following criteria:

   1. Hemoglobin (Hgb) > 8 g/dL
   2. Absolute Neutrophil Count (ANC) > 1000/mm3
   3. Platelet count > 100,000/mm3
   4. Blood Urea Nitrogen (BUN) < 30 mg/dL
   5. Creatinine < 2 mg/dL
   6. Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2 x upper limit of normal (ULN)
   7. Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6x unless therapeutically warranted
6. Subjects must use effective contraceptive methods during the study and for three months following the last dose of study product, if of reproductive age and still retain fertility potential.
7. Subjects must have at least one positive DTH skin response (more than 5 mm) to test item challenge prior to randomization.

Exclusion Criteria:

1. Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia).
2. Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)
3. Subjects with concurrent conditions that would jeopardize the safety of the subject or compliance with the protocol.
4. Subjects with a history of chronic or acute hepatitis C or B infection.
5. Subjects require or are likely to require more than a 2-week course of corticosteroids for intercurrent illness. Subjects must have completed the course of corticosteroids at the time of apheresis to meet eligibility.
6. Subjects have any acute infection that requires specific therapy. Acute therapy must have been completed within seven days prior to study enrollment.
7. Subjects with active other malignancy diagnosed in the past 3 years (excepting in situ tumors)
8. Subjects known to be pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ). ICT-107 will be given once a week for 4 weeks in the induction phase. During the maintenance phase, ICT-107 will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.	Biological: ICT-107; Autologous dendritic cells pulsed with peptides associated with tumor antigens
Placebo Comparator: 2; Arm 2 will receive TMZ with a blinded control. Control will be given once a week for 4 weeks in the induction phase. During the maintenance phase, Control will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.	Biological: Placebo; Control, autologous monocytes-enriched PBMC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS) of subjects treated with ICT-107 and standard of care (radiation (RT) and TMZ) vs. placebo control and standard of care (RT and TMZ)	46 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival in patients with unmethylated MGMT tumors	OS of subjects with unmethylated MGMT (O6-methylguanine-DNA methyltransferase) tumors treated with ICT-107 and standard of care vs. control and standard of care	46 months
Overall survival in patients with methylated MGMT (O6-methylguanine-DNA methyltransferase) tumors	OS of subjects with methylated MGMT tumors treated with ICT-107 and standard of care vs. control and standard of care.	46 months
Progression-free survival	Progression-free survival (PFS) of subjects treated with ICT-107 and standard of care vs. control and standard of care	46 months
Type and frequency of treatment emergent adverse events	Compare the type and frequency of treatment emergent adverse events of ICT-107 vs. control treatment groups	46 months

Collaborators and Investigators

• Sponsor: Precision Life Sciences Group
• Collaborators: Medelis Inc.

Publications and helpful links

General Publications

• Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuno MA, Richardson JE, Fan X, Ji J, Chu RM, Bender JG, Hawkins ES, Patil CG, Black KL, Yu JS. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother. 2013 Jan;62(1):125-35. doi: 10.1007/s00262-012-1319-0. Epub 2012 Jul 31.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 7, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimated): September 10, 2015

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: ICT-107-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No