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

• ClinicalTrials.gov Identifier: NCT04485949
• Recruitment Status: Recruiting
• First Posted: July 24, 2020
• Last Update Posted: March 5, 2024
• Sponsor: Imvax
• Information provided by (Responsible Party): Imvax

Tracking Information

• First Submitted Date: July 22, 2020
• First Posted Date: July 24, 2020
• Last Update Posted Date: March 5, 2024
• Actual Study Start Date: March 20, 2023
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2023)

Progression-free Survival (PFS) [ Time Frame: Up to 36 months ]

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.

Original Primary Outcome Measures (submitted: July 22, 2020)

Progression-free Survival (PFS) [ Time Frame: Up to 36 months ]

PFS is defined as the time from randomization to event or censoring.

Current Secondary Outcome Measures (submitted: October 17, 2023)

• Overall Survival (OS) [ Time Frame: Up to 48 months ]
  OS is defined as the time from randomization to death due to any cause.
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Device Events (ADE), and Unexpected Adverse Device Events (ADR) [ Time Frame: Up to 36 months ]
  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.
• Number of Participants With Clinically Significant Laboratory Assessment Abnormalities [ Time Frame: Up to 36 months ]
• Number of Participants With Clinically Significant Vital Signs Measurements [ Time Frame: Up to 36 months ]
• Number of Participants With Clinically Significant Physical Examination Findings [ Time Frame: Up to 36 months ]

Original Secondary Outcome Measures (submitted: July 22, 2020)

• Overall Survival (OS) [ Time Frame: Up to 48 months ]
  OS is defined as the time from randomization to death due to any cause.
• PFS in Participants With O6-methylguanine-DNA Methyltransferase (MGMT) With Methylation [MGMT+] and MGMT Without Methylation [MGMT-] [ Time Frame: Up to 36 months ]
  PFS is defined as the time from randomization to event or censoring. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.
• OS in Participants With MGMT+ and MGMT- [ Time Frame: Up to 48 months ]
  OS is defined as the time from randomization to death due to any cause. MGMT status will be determined per epigenetic analysis from tissue obtained during surgery.
• Change From Baseline in Participant-reported Quality of Life (QoL) Questionnaires Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Lif questionnaire (QLQ) -C30 Scores [ Time Frame: Baseline, Month 36 ]
  EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
• Change From Baseline in Participant-reported QoL Questionnaires Based on EORTC QLQ Brain Module (EORTC QLQ-BN20) Scores [ Time Frame: Baseline, Month 36 ]
  The QLQ-BN20 is a questionnaire specifically designed as the QLQ-C30 supplement for the evaluation of quality of life in brain tumor participants. It includes 4 multi-item sub-scales: future uncertainty, visual disorder, motor dysfunction, communication deficits, and 7 single-item scales: headaches, seizures, drowsiness, itchy skin, hair loss, weakness of legs, and bladder control. All items are rated on a 4-point Likert-type scale ('1=not at all', '2=a little', '3=quite a bit' and '4=very much'), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
• Change From Baseline in Mini-Mental Status Examination (MMSE) Scores [ Time Frame: Baseline, Month 36 ]
  The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance.
• Time to Definitive Deterioration Karnofsky Performance Status (KPS) Score [ Time Frame: Baseline until KPS deterioration (up to 36 months) ]
  Time to KPS deterioration was defined as the time from screening to the first date of deterioration of the KPS score. Deterioration of KPS is defined as a stable or increasing steroid dose-dependent stabilization of a KPS score of <70 over 2 consecutive visits no more than 2 months apart. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months or until the last progression visit, whichever comes first ]
  An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 from mild (Grade 1) to death (Grade 5). SAE is an AE or adverse reaction which is considered serious if it results in any of the following outcomes: death, life-threatening AE, require hospitalizations or prolongation of hospitalizations, results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect and is a medically important event.
• Number of Participants With Clinically Significant Laboratory Assessment Abnormalities [ Time Frame: Up to 12 months or until the last progression visit, whichever comes first ]
• Number of Participants With Clinically Significant Vital Signs Measurements [ Time Frame: Up to 12 months or until the last progression visit, whichever comes first ]
• Number of Participants With Clinically Significant Physical Examination Findings [ Time Frame: Up to 12 months or until the last progression visit, whichever comes first ]

Current Other Pre-specified Outcome Measures (submitted: March 17, 2023)

• Time to Deterioration of Karnofsky Performance Status (KPS) Score [ Time Frame: Up to 36 months ]
  Time to KPS deterioration is defined as the time from screening to the first date of deterioration of the KPS score. Deterioration of KPS is defined as a stable or increasing steroid dose-dependent stabilization of a KPS score of <70 over 2 consecutive visits at least 4 weeks apart. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.
• PFS in Participants With O6-methylguanine-DNA Methyltransferase (MGMT) With Methylation [MGMT+] and MGMT Without Methylation [MGMT-] [ Time Frame: Up to 36 months ]
  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. MGMT status will be determined per epigenetic and tumor proliferation analysis from tissue obtained during surgery.
• OS in Participants With MGMT+ and MGMT- [ Time Frame: Up to 48 months ]
  OS is defined as the time from randomization to death due to any cause. MGMT status will be determined per epigenetic and tumor proliferation analysis from tissue obtained during surgery.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2b Clinical Study With a Combination Immunotherapy in Newly Diagnosed Patients With Glioblastoma
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Glioblastoma

Intervention

• Combination Product: IGV-001 Cell Immunotherapy
  IGV-001, an immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers.
• Combination Product: Placebo
  Placebo in implantable biodiffusion chambers containing a predetermined inactive solution.
• Procedure: Standard of Care (SOC): Radiation Therapy
  Radiation therapy administered per institutional standards.
• Drug: SOC: Temozolomide
  Temozolomide administered orally.

Study Arms

• Experimental: IGV-001
  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).
  Interventions:

  • Combination Product: IGV-001 Cell Immunotherapy
  • Procedure: Standard of Care (SOC): Radiation Therapy
  • Drug: SOC: Temozolomide
• Placebo Comparator: Placebo
  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).
  Interventions:

  • Combination Product: Placebo
  • Procedure: Standard of Care (SOC): Radiation Therapy
  • Drug: SOC: Temozolomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 22, 2020): 93
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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®

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Madhavi Diwanji; +1 2679004110; contact@imvax.com; m.diwanji@imvax.com

Contact: Jill Krause; j.krause@imvax.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04485949
• Other Study ID Numbers: 14379-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Imvax
• Original Responsible Party: Same as current
• Current Study Sponsor: Imvax
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Imvax
• Verification Date: March 2024