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

April 27, 2026 updated by: NovoCure GmbH

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).

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

741

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • The Ottawa Hospital Cancer Centre
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H2X 3E4
      • Montreal, Quebec, Canada, H3A 2B4
        • Recruiting
        • Montreal Neurological Institute-Hospital, Clinical Research Unit
        • Contact:
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Recruiting
        • Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie-CHUS)
        • Contact:
  • Czechia
      • Prague, Czechia, 150 30
  • France
      • Bron, France, 69500
        • Recruiting
        • Centre Hospitalier Universitaire de Lyon
        • Principal Investigator:
          • François DUCRAY
        • Contact:
      • Marseille, France, 13385
        • Recruiting
        • Hopital de la Timone
        • Principal Investigator:
          • Emeline TABOURET
        • Contact:
      • Paris, France, 75010
        • Recruiting
        • Hôpital Saint-Louis
        • Principal Investigator:
          • Stefania Cuzzubbo
        • Contact:
      • Paris, France, 75013
        • Recruiting
        • Groupe Hospitalier Pitie - Salpetriere
        • Contact:
        • Principal Investigator:
          • Khe Hoang-Xuan
      • Toulouse, France, 31059
        • Recruiting
        • Institut Claudius Regaud
        • Contact:
        • Principal Investigator:
          • Elizabeth Moyal
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charité Campus Virchow-Klinikum
        • Contact:
      • Essen, Germany, 45147
        • Recruiting
        • Universitatsklinikum Essen
        • Contact:
      • Frankfurt, Germany, 60528
        • Recruiting
        • University Hospital Frankfurt
        • Contact:
  • Israel
      • Haifa, Israel, 3109601
      • Petah Tikva, Israel, 4941492
        • Recruiting
        • Rabin Medical Center- Beilinson Hospital
        • Contact:
        • Principal Investigator:
          • Shlomit Yust-Katz
      • Ramat Gan, Israel, 5265601
      • Tel Aviv, Israel, 64239
        • Recruiting
        • Tel-Aviv Sourasky Medical Center
        • Contact:
        • Principal Investigator:
          • Deborah Blumenthal
  • Italy
      • Bologna, Italy, 40139
        • Recruiting
        • Ospedale Bellaria
        • Contact:
      • Milan, Italy, 20133
      • Naples, Italy, 80147
      • Padova, Italy, 35128
        • Recruiting
        • UOC Oncologia Medica 1 Istituto Oncologico Veneto IOV-IRCCS
        • Contact:
      • Rozzano, Italy, 20089
      • Siena, Italy, 53100
        • Recruiting
        • U.O.C. Immunoterapia Oncologica A.O.U. Senese, Policlinico Santa Maria alle Scotte
        • Contact:
    • Torino
      • Torino, Torino, Italy, 10126
        • Recruiting
        • Neuro-Oncologia Clinica Ospedale Molinette - AOU Città della Salute e della Scienza di Torino
        • Contact:
        • Contact:
          • Phone Number: +39.011-633.4904
  • Japan
      • Fukuoka, Japan, 812-8582
      • Hokkaido, Japan, 060-8648
      • Ishikawa, Japan, 920-8641
      • Kumamoto, Japan, 860-8556
      • Kyoto, Japan, 606-8507
      • Mitaka, Japan, 181-8611
      • Nagoya, Japan, 466-8560
      • Saitama, Japan, 350-1298
        • Recruiting
        • Saitama Medical University International Medical Center
        • Contact:
      • Sendai, Japan, 980-8574
      • Tokyo, Japan, 104-0045
    • Kanagawa
      • Isehara, Kanagawa, Japan, 259-1193
        • Recruiting
        • Tokai University Hospital
        • Contact:
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Recruiting
        • Centrum Onkologii
        • Contact:
      • Gliwice, Poland, 44-102
      • Lodz, Poland, 93-513
        • Recruiting
        • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika-Zakład Teleradioterapii
        • Contact:
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
      • Barcelona, Spain, 08908
        • Recruiting
        • Institut Català d'Oncologia de L'Hospitalet (ICO L'Hospitalet)
        • Contact:
      • Córdoba, Spain, 14004
        • Recruiting
        • Hospital Universitario Reina Sofía
        • Contact:
      • Granada, Spain, 18014
        • Recruiting
        • Hospital Universitario Virgen de las Nieves
        • Contact:
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon y Cajal
        • Contact:
          • María Ángeles Vaz Salgado
          • Phone Number: (+34) 91 336 82 63
          • Email: mavaz4@gmail.com
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
      • Madrid, Spain, 28046
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio
        • Contact:
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari i Politècnic La Fe
        • Contact:
    • Madrid
      • Madrid, Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Clínico San Carlos
        • Contact:
      • Madrid, Madrid, Spain, 28040
        • Enrolling by invitation
        • Hospital Universitario Clínico San Carlos
  • Switzerland
      • Basel, Switzerland, 4031
        • Recruiting
        • University Hospital Basel Medical Oncology
        • Contact:
      • Lausanne, Switzerland, 1005
        • Recruiting
        • Centre Hospitalier Universitaire Vaudois (CHUV)
        • Contact:
      • Zurich, Switzerland, 8091
        • Recruiting
        • University Hospital Zurich
        • Contact:
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrooke's Hospital (Cambridge University Hospitals NHS Foundation Trust)
        • Principal Investigator:
          • Fiona Harris
        • Contact:
      • Cardiff, United Kingdom, CF14 2TL
      • Edinburgh, United Kingdom, EH4 2XU
        • Recruiting
        • Western General Hospital
        • Contact:
      • Liverpool, United Kingdom, L7 8YA
        • Recruiting
        • The Clatterbridge Cancer Centre (Clatterbridge Cancer Centre NHS Foundation Trust)
        • Contact:
      • Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie Hospital
        • Contact:
      • Sheffield, United Kingdom, S10 2SJ
      • Southampton, United Kingdom, SO16 6YD
        • Recruiting
        • Southampton General Hospital
        • Contact:
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden
        • Principal Investigator:
          • Liam Welsh
        • Contact:
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital
        • Contact:
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • University of Southern California
        • Contact:
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Hoag Memorial Hospital Presbyterian
        • Contact:
          • Simon Khagi
        • Contact:
      • Palo Alto, California, United States, 94305
        • Recruiting
        • Stanford Cancer Institute
        • Contact:
        • Principal Investigator:
          • Lawrence Recht
      • San Francisco, California, United States, 94143
    • Florida
      • Gainesville, Florida, United States, 32608
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic - Florida
        • Contact:
      • Miami, Florida, United States, 33176
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Patrick Grogan
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky Medical Center
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Recruiting
        • Tufts Medical Center
        • Principal Investigator:
          • Suriya Jeyapalan
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • Masonic Cancer Center, University of Minnesota
        • Principal Investigator:
          • Elizabeth Neil
        • Contact:
          • Elizabeth Neil
          • Phone Number: (612)-625-5317
          • Email: neile@umn.edu
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic - Rochester
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Contact:
    • Nevada
      • Reno, Nevada, United States, 89502
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • John Theurer Cancer Center/ Hackensack Meridian Health
        • Principal Investigator:
          • Deric Park
        • Contact:
    • New York
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health
        • Principal Investigator:
          • Samuel Singer
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Principal Investigator:
          • Fabio Iwamoto
        • Contact:
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center- Montefiore Medical Park
        • Contact:
        • Principal Investigator:
          • Adilia Hormigo
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Katherine Peters
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
        • Contact:
        • Principal Investigator:
          • Herbert Newton
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • The Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • Mark Malkin
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Clinical Trials Organization
        • Contact:
        • Principal Investigator:
          • Iyad Alnahhas
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
        • Contact:
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Principal Investigator:
          • Eric Wong
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas, MD Anderson Cancer Center
        • Principal Investigator:
          • Chirag Patel
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute, University of Utah
        • Principal Investigator:
          • Howard Colman
        • Contact:
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98122
        • Recruiting
        • Swedish Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 not 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 24 months
Overall survival (OS) is defined as the time from randomization to death due to any cause
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) per RANO 2.0 assessed by investigator
Time Frame: 24 months

PFS is defined as the time interval, in months, between randomization and the first documented disease progression per RANO 2.0 assessed by investigator or death due to any cause, whichever occurs first.

Note: RANO 2.0 = Modified Radiographic Response Assessment in Neuro-Oncology
24 months
Progression-Free Survival (PFS) per RANO 2.0 assessed by investigator
Time Frame: 24 months

PFS is defined as the time interval, in months, between randomization and the first documented disease progression per RANO 2.0 assessed by investigator or death due to any cause, whichever occurs first.

Note: RANO 2.0 = Response Assessment in Neuro-Oncology
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NovoCure GmbH

Collaborators

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 3, 2025

Primary Completion (Estimated)

April 1, 2029

Study Completion (Estimated)

April 1, 2029

Study Registration Dates

First Submitted

August 13, 2024

First Submitted That Met QC Criteria

August 13, 2024

First Posted (Actual)

August 16, 2024

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EF-41
  • 2024-513550-30-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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