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

August 17, 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
    • Alberta
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Recruiting
        • Hamilton Health Sciences-Juravinski Cancer Centre
        • Contact:
          • Ronald Ramos
          • Phone Number: 44657 (905) 521-2100
          • Email: ramosr@hhsc.ca
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • The Ottawa Hospital Cancer Centre
        • Contact:
      • Toronto, Ontario, Canada, M5G 2C1
        • Recruiting
        • University Health Network - Princess Margaret 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
        • Active, not recruiting
        • Nemocnice na Homolce
  • France
      • Bron, France, 69500
        • Active, not recruiting
        • Centre Hospitalier Universitaire de Lyon
      • Marseille, France, 13385
        • Active, not recruiting
        • Hopital de la Timone
      • Paris, France, 75010
        • Active, not recruiting
        • Hôpital Saint-Louis
      • Paris, France, 75013
        • Active, not recruiting
        • Groupe Hospitalier Pitie - Salpetriere
      • Toulouse, France, 31059
        • Active, not recruiting
        • Institut Claudius Regaud
  • Germany
      • Berlin, Germany, 10117
        • Active, not recruiting
        • Charité Campus Virchow-Klinikum
      • Essen, Germany, 45147
        • Active, not recruiting
        • Universitatsklinikum Essen
      • Frankfurt, Germany, 60528
        • Active, not recruiting
        • University Hospital Frankfurt
  • Israel
      • Haifa, Israel, 3109601
        • Active, not recruiting
        • Rambam Medical Center
      • Petah Tikva, Israel, 4941492
        • Active, not recruiting
        • Rabin Medical Center- Beilinson Hospital
      • Ramat Gan, Israel, 5265601
        • Active, not recruiting
        • Chaim Sheba Medical Center
      • Tel Aviv, Israel, 64239
        • Active, not recruiting
        • Tel-Aviv Sourasky Medical Center
  • Italy
      • Bologna, Italy, 40139
        • Active, not recruiting
        • Ospedale Bellaria
      • Milan, Italy, 20133
        • Active, not recruiting
        • Fondazione IRCCS Istituto Neurologico Carlo BEsta
      • Naples, Italy, 80147
        • Active, not recruiting
        • Ospedale del Mare
      • Padova, Italy, 35128
        • Active, not recruiting
        • UOC Oncologia Medica 1 Istituto Oncologico Veneto IOV-IRCCS
      • Rozzano, Italy, 20089
        • Active, not recruiting
        • IRCCS Istituto Clinico Humanitas
      • Siena, Italy, 53100
        • Active, not recruiting
        • U.O.C. Immunoterapia Oncologica A.O.U. Senese, Policlinico Santa Maria alle Scotte
    • Torino
      • Torino, Torino, Italy, 10126
        • Active, not recruiting
        • Neuro-Oncologia Clinica Ospedale Molinette - AOU Città della Salute e della Scienza di Torino
  • 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
    • Aichi-ken
      • Toyoake-shi, Aichi-ken, Japan, 470-1192
        • Recruiting
        • Fujita Health University Hospital
        • Contact:
    • Kanagawa
      • Isehara, Kanagawa, Japan, 259-1193
        • Recruiting
        • Tokai University Hospital
        • Contact:
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Active, not recruiting
        • Centrum Onkologii
      • Gliwice, Poland, 44-102
        • Active, not recruiting
        • Narodowy Instytut Onkologii
      • Lodz, Poland, 93-513
        • Active, not recruiting
        • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika-Zakład Teleradioterapii
  • Spain
      • Barcelona, Spain, 08035
        • Active, not recruiting
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08908
        • Active, not recruiting
        • Institut Català d'Oncologia de L'Hospitalet (ICO L'Hospitalet)
      • Córdoba, Spain, 14004
        • Active, not recruiting
        • Hospital Universitario Reina Sofia
      • Granada, Spain, 18014
        • Active, not recruiting
        • Hospital Universitario Virgen de las Nieves
      • Madrid, Spain, 28041
        • Active, not recruiting
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Active, not recruiting
        • Hospital Universitario La Paz
      • Madrid, Spain, 28034
        • Active, not recruiting
        • Hospital Universitario Ramon y Cajal
      • Seville, Spain, 41013
        • Active, not recruiting
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46026
        • Active, not recruiting
        • Hospital Universitari i Politècnic La Fe
    • Madrid
      • Madrid, Madrid, Spain, 28040
        • Active, not recruiting
        • Hospital Universitario Clinico San Carlos
  • Switzerland
      • Basel, Switzerland, 4031
        • Active, not recruiting
        • University Hospital Basel Medical Oncology
      • Lausanne, Switzerland, 1005
        • Active, not recruiting
        • Centre Hospitalier Universitaire Vaudois (CHUV)
      • Zurich, Switzerland, 8091
        • Active, not recruiting
        • University Hospital Zurich
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Active, not recruiting
        • Queen Elizabeth
      • Cambridge, United Kingdom, CB2 0QQ
        • Active, not recruiting
        • Addenbrooke's Hospital (Cambridge University Hospitals NHS Foundation Trust)
      • Cardiff, United Kingdom, CF14 2TL
        • Active, not recruiting
        • Velindre Cancer Centre
      • Edinburgh, United Kingdom, EH4 2XU
        • Active, not recruiting
        • Western General Hospital
      • Liverpool, United Kingdom, L7 8YA
        • Active, not recruiting
        • The Clatterbridge Cancer Centre (Clatterbridge Cancer Centre NHS Foundation Trust)
      • Manchester, United Kingdom, M20 4BX
        • Active, not recruiting
        • The Christie Hospital
      • Sheffield, United Kingdom, S10 2SJ
        • Active, not recruiting
        • Weston Park Hospital
      • Southampton, United Kingdom, SO16 6YD
        • Active, not recruiting
        • Southampton General Hospital
      • Sutton, United Kingdom, SM2 5PT
        • Active, not recruiting
        • Royal Marsden
    • Greater London
      • London, Greater London, United Kingdom, W6 8RF
        • Active, not recruiting
        • Charing Cross Hospital
    • Middlesex
      • Northwood, Middlesex, United Kingdom, HA6 2RN
        • Active, not recruiting
        • Mount Vernon Cancer Centre
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Active, not recruiting
        • Mayo Clinic Hospital
    • California
      • Los Angeles, California, United States, 90033
        • Active, not recruiting
        • University of Southern California
      • Newport Beach, California, United States, 92663
        • Active, not recruiting
        • Hoag Memorial Hospital Presbyterian
      • Palo Alto, California, United States, 94305
        • Active, not recruiting
        • Stanford Cancer Institute
      • San Francisco, California, United States, 94143
        • Active, not recruiting
        • University of California
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Active, not recruiting
        • MedStar Georgetown University Hospital
    • Florida
      • Gainesville, Florida, United States, 32608
        • Active, not recruiting
        • UF Health Neuromedicine
      • Jacksonville, Florida, United States, 32224
        • Active, not recruiting
        • Mayo Clinic - Florida
      • Miami, Florida, United States, 33176
        • Active, not recruiting
        • Miami Cancer Institute
      • Tampa, Florida, United States, 33612
        • Active, not recruiting
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Active, not recruiting
        • Northwestern Memorial Hospital
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Active, not recruiting
        • University of Kentucky Medical Center
      • Louisville, Kentucky, United States, 40241
        • Active, not recruiting
        • Norton Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Active, not recruiting
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Active, not recruiting
        • Tufts Medical Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Active, not recruiting
        • Masonic Cancer Center, University of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Active, not recruiting
        • Mayo Clinic - Rochester
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Active, not recruiting
        • Washington University
    • Nevada
      • Reno, Nevada, United States, 89502
        • Active, not recruiting
        • Renown Regional Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Active, not recruiting
        • John Theurer Cancer Center/ Hackensack Meridian Health
      • New Brunswick, New Jersey, United States, 08901
        • Active, not recruiting
        • Rutgers Cancer Institute of New Jersey University Hospital
    • New York
      • Lake Success, New York, United States, 11042
        • Active, not recruiting
        • Northwell Health
      • New York, New York, United States, 10032
        • Active, not recruiting
        • Columbia University Irving Medical Center
      • The Bronx, New York, United States, 10461
        • Active, not recruiting
        • Montefiore Medical Center- Montefiore Medical Park
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Active, not recruiting
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Active, not recruiting
        • University of Cincinnati Cancer Institute
      • Cleveland, Ohio, United States, 44106
        • Active, not recruiting
        • University Hospitals Cleveland Medical Center
      • Cleveland, Ohio, United States, 44195
        • Active, not recruiting
        • The Cleveland Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Active, not recruiting
        • Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Clinical Trials Organization
      • Pittsburgh, Pennsylvania, United States, 15232
        • Active, not recruiting
        • UPMC Hillman Cancer Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Active, not recruiting
        • Rhode Island Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • The University of Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • University of Texas, MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Active, not recruiting
        • Huntsman Cancer Institute, University of Utah
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Active, not recruiting
        • Inova Schar Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98122
        • Active, not recruiting
        • Swedish Medical Center

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.
Other Names:
  • KEYTRUDA®

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)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 17, 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)
  • MK3475-D58 (Other Identifier: Merck Sharp & Dohme LLC)
  • KEYNOTE D58 (Other Identifier: Merck Sharp & Dohme LLC)

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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