EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma

Purpose

This is a multicenter, two-arm, randomized, double-blind, placebo-controlled study of Optune® (Tumor Treating Fields at 200 kHz) together with maintenance Temozolomide (TMZ) chemotherapy agent and pembrolizumab compared to Optune® together with maintenance TMZ and placebo in newly diagnosed Glioblastoma (GBM) patients. The primary objective of the study is to evaluate the Overall Survival (OS).

Condition

  • Glioblastoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. The participant (or legally acceptable representative) has provided documented informed consent for the study. 2. Be ≥ 18 years of age on day of providing informed consent. 3. Participant with new diagnosis of GBM according to World Health Organization (WHO) 2021 Classification. 4. 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. 5. Have completed standard adjuvant chemoradiotherapy of radiotherapy (RT) according to local practice (56-64 Gy), and concomitant TMZ chemotherapy. 6. Amenable to treatment with Optune concomitant with maintenance TMZ (150-200 mg/m^2 daily x 5, Q28 days). 7. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days before randomization. 8. Stable or decreasing dose of corticosteroids (dexamethasone ≤ 2mg or equivalent) for the last 7 days prior to randomization, if applicable.

Exclusion Criteria

  1. Has received prior therapy with an anti-Programmed Cell Death 1 (PD-1), anti- Programmed Cell Death-Ligand 1(PD-L1), or anti Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4), OX 40, CD137). 2. Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial mass effect. 3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. 4. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. 5. 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. 6. 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. 7. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 8. Early progressive disease after the end of TMZ/RT. If pseudo progression is suspected, additional imaging studies should be performed to rule out true progression. 9. Infratentorial or leptomeningeal disease.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
The participants in the study will be randomized in a ratio of 2:1 in favor of the treatment group to one of the following groups: Treatment Group - Optune concomitant with maintenance TMZ and pembrolizumab. Control Group - Optune concomitant with maintenance TMZ and placebo.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Treatment Group
  • Device: Optune® device
    Optune® device delivering TTFields therapy at 200 kHz.
    Other names:
    • TTFields
  • Drug: Temozolomide
    Temozolomide per approved labeling.
  • Drug: Pembrolizumab
    Pembrolizumab dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles.
Placebo Comparator
Control Group
  • Device: Optune® device
    Optune® device delivering TTFields therapy at 200 kHz.
    Other names:
    • TTFields
  • Drug: Temozolomide
    Temozolomide per approved labeling.
  • Drug: Placebo
    Placebo (saline solution) dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles.

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky Medical Center
Lexington, Kentucky 40536
Contact:
John Villano
312-996-6651
jlvillano@uky.edu

More Details

NCT ID
NCT06556563
Status
Recruiting
Sponsor
NovoCure GmbH

Study Contact

Doron Manzur
1-877-678-8611
clinicaltrials@novocure.com