A Phase 2b Clinical Study With a Combination Immunotherapy in Newly Diagnosed Patients With Glioblastoma

Study Overview
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Brief Summary
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The purpose of this study is to assess progression-free survival (PFS) and overall survival (OS) in newly diagnosed Glioblastoma (GBM) participants treated with IGV-001 as compared with placebo.

Official Title
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A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 2b Study to Assess the Safety and Efficacy of IGV-001, an Autologous Cell Immunotherapy With Antisense Oligonucleotide (IMV-001) Targeting IGF-1R, in Newly Diagnosed Patients With Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Combination Product: IGV-001 Cell Immunotherapy
* Combination Product: Placebo
* Procedure: Standard of Care (SOC): Radiation Therapy
* Drug: SOC: Temozolomide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Has a Karnofsky performance scale (KPS) score ≥ 70 at screening Has a new diagnosis of GBM (WHO GRADE III or Grade IV GBM) based on the treating neurosurgeon's best clinical judgement Has a diagnostic contrast-enhanced magnetic resonance imaging (MRI) scan with fluid attenuated inversion-recovery (FLAIR) sequence of the brain at screening. Participants must have a confirmed measurable disease pre-operatively with at least 1 lesion measuring a total bi-perpendicular product of 4 centimeter square (cm^2) in 2 different planes (axial, sagittal, or coronal) The tumor must be located in the supratentorial compartment Has adequate bone marrow and organ function at screening Key Exclusion Criteria: Has bi-hemispheric disease, multicentric disease, or disease burden involving the brain stem or cerebellum based on MRI post-gadolinium enhancement Has received any previous surgical resection or any anticancer intervention for glioma Has any history of glioma, a concurrent malignancy, or malignancy within 3 years of randomization, unless definitive therapy is completed, with the exception of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy Has any severe immunocompromised condition (eg, human immunodeficiency virus (HIV) with a cluster of differentiation [CD] 4+ cell count <200*10^6/liter [L]) or any active uncontrolled autoimmune disease (eg, Crohn's disease) Has an active cardiac disease or a history of cardiac dysfunction Is receiving any other investigational agent(s) or has received an investigational agent within 30 days or 5 half-lives of investigational agent use, whichever is longer, prior to screening Is partaking in another interventional study. Participants who are partaking in an observational study are eligible Has received a live vaccine within 30 days of screening Has active and uncontrolled/untreated hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, or any other active infections that, in the Investigator's opinion, would impair or prohibit a participant's participation in this study. Is receiving treatment with Tumor Treating Fields or Optune®

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IGV-001<br>Participants will be implanted with biodiffusion chambers containing IGV-001 on Day 1 and explanted on Day 3 (at approximately 48 hours following implantation). After 6 weeks, participants will receive radiotherapy (RT) per institutional standards for 5 days per week along with temozolomide 75 mg/m^2 orally, once daily (QD) for up to 12 weeks followed by temozolomide 150 to 200 mg/m^2, orally, on Days 1 to 5 of each 28-day cycle for up to 6 cycles (Week 41). | Combination Product: IGV-001 Cell Immunotherapy<br>* IGV-001, an immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers.<br>Procedure: Standard of Care (SOC): Radiation Therapy<br>* Radiation therapy administered per institutional standards.<br>Drug: SOC: Temozolomide<br>* Temozolomide administered orally.<br>|
| Placebo Comparator: Placebo<br>Participants will be implanted with biodiffusion chambers containing placebo on Day 1 and explanted on Day 3 (at approximately 48 hours following implantation). After 6 weeks, participants will receive RT per institutional standards for 5 days per week along with temozolomide 75 mg/m^2 orally, QD for up to 12 weeks followed by temozolomide 150 to 200 mg/m^2, orally, on Days 1 to 5 of each 28-day cycle for up to 6 cycles (Week 41). | Combination Product: Placebo<br>* Placebo in implantable biodiffusion chambers containing a predetermined inactive solution.<br>Procedure: Standard of Care (SOC): Radiation Therapy<br>* Radiation therapy administered per institutional standards.<br>Drug: SOC: Temozolomide<br>* Temozolomide administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the time from randomization to first progression, as determined by the central radiology review group blinded to the study treatment arm, or death. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to 48 months | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Device Events (ADE), and Unexpected Adverse Device Events (ADR) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a product, which does not have a causal relationship with treatment. AEs will be graded according to Common Terminology Criteria for Adverse Events, version 5.0 from mild(Grade 1) to death(Grade 5). SAE is an AE which is considered serious if it results in any of the following outcomes: death, life-threatening AE, require hospitalizations/prolongation of hospitalizations, results in persistent or significant disability; results in a congenital anomaly and is a medically important event. An ADE is defined as any AE caused by or associated with use of a device and suspected to be resulting from insufficiencies in the instructions for use, the deployment, the implantation, the installation, the operation, or any malfunction of the medical device. An Unexpected ADR is defined as an adverse reaction, nature or severity of which is not consistent with product information. | Up to 36 months | 
| Number of Participants With Clinically Significant Laboratory Assessment Abnormalities |  | Up to 36 months | 
| Number of Participants With Clinically Significant Vital Signs Measurements |  | Up to 36 months | 
| Number of Participants With Clinically Significant Physical Examination Findings |  | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly Diagnosed