Clinical Trial 23369

• Overview

  Study Title:

  A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Optune® (TTFields, 200 kHz) Concomitant with Maintenance Temozolomide and Pembrolizumab Versus Optune® Concomitant with Maintenance Temozolomide and Placebo for the Treatment of Newly Diagnosed Glioblastoma (EF-41/KEYNOTE D58)

  Objective:

  Objective: To compare overall survival (OS) for subjects treated with Optune concomitant with maintenance temozolomide (TMZ) plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo Hypothesis: Optune concomitant with maintenance TMZ plus pembrolizumab is superior to Optune concomitant with maintenance TMZ plus placebo with respect to OS Objective: To evaluate progression-free survival (PFS) per modified response assessment in neuro-oncology criteria (mRANO) as assessed locally by the investigator for subjects treated with Optune concomitant with maintenance TMZ plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo Objective: To evaluate PFS per response assessment in neuro-oncology criteria (RANO) as assessed locally by the investigator for subjects treated with Optune concomitant with maintenance TMZ plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo Objective: To evaluate PFS rate at 6 months (PFS6m) and at 12 months (PFS12m) per mRANO as assessed locally by the investigator. Objective: To evaluate next PFS (PFS2) per mRANO as assessed locally by the investigator. Objective: To evaluate 1- and 2-year survival rates Exploratory Objective: To evaluate the pathological changes in resected GBM tumors Objective: To evaluate immunological changes in the blood Objective: To evaluate genomic signatures related to response Objective: To evaluate PFS, PFS6m, PFS12m, PFS2 per mRANO as assessed locally by the investigator, OS, 1-year survival rate and 2-year survival rate in a modified Intention -to-Treat (mITT) population

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy

  Medications:

  Pembrolizumab (Keytruda); Placebo (); Temodal (Temozolomide); Temozolomide ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • The participant (or legally acceptable representative) has provided documented informed consent for the study.
  • Be 18 years of age on day of providing informed consent.
  • Participant with new diagnosis of GBM according to WHO 2021 Classification.
  • Recovered from maximal debulking surgery (gross total resection, partial resection and biopsy-only patients are all acceptable), Gliadel wafers placement at the time of surgical resection is allowed.
  • Have completed standard adjuvant chemoradiotherapy of RT according to local practice (56-64 Gy), and concomitant TMZ chemotherapy.
  • Able to start treatment at least 4 weeks from the later of last dose of concomitant temozolomide or radiotherapy.
  • Amenable to treatment with Optune concomitant with maintenance temozolomide (150-200 mg/m^2 daily x 5, Q28 days).
  • All patients must have had tissue submitted for MGMT Promoter Methylation determination prior to randomization.
  • Have an ECOG Performance Status of 0 to 1 assessed within 7 days before randomization.
  • Stable or decreasing dose of corticosteroids (dexamethasone 2mg or equivalent) for the last 7 days prior to randomization, if applicable.
  • Have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to randomization.
  • Able to have MRI with contrast of the brain.
  • Additional criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
  • Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial mass effect.
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to Participants with endocrine- one replacement may be eligible. Note: If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention.
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to Section 6.5.1 for information on COVID-19 vaccines
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first study treatment.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV), Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has had an allogenic tissue/solid organ transplant.
  • Early progressive disease after the end of TMZ/RT. If pseudoprogression is suspected, additional imaging studies should be performed to rule out true progression.
  • Infratentorial or leptomeningeal disease.
  • Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
  • A skull defect (such as, missing bone with no replacement) or bullet fragments.
  • Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness).
  • Known allergies to medical adhesives or hydrogel and/or compounds of similar chemical or biologic composition to Temozolomide.
  • Admitted to an institution by administrative or court order.
  • Additional criteria may apply.

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