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

November 4, 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

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
741

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Hamilton Health Sciences-Juravinski Cancer Centre
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Canada, M5G 2C1
        • University Health Network - Princess Margaret Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H2X 3E4
        • CHUM
      • Montreal, Quebec, Canada, H3A 2B4
        • Montreal Neurological Institute-Hospital, Clinical Research Unit
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie-CHUS)
  • Czechia
      • Prague, Czechia, 150 30
        • Nemocnice Na Homolce
  • France
      • Bron, France, 69500
        • Centre Hospitalier Universitaire de Lyon
      • Marseille, France, 13385
        • Hopital de la Timone
      • Paris, France, 75010
        • Hopital Saint-Louis
      • Paris, France, 75013
        • Groupe Hospitalier Pitie - Salpetriere
      • Toulouse, France, 31059
        • Institut Claudius Regaud
  • Germany
      • Berlin, Germany, 10117
        • Charité Campus Virchow-Klinikum
      • Essen, Germany, 45147
        • Universitätsklinikum Essen
      • Frankfurt, Germany, 60528
        • University Hospital Frankfurt
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Medical Center
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center- Beilinson Hospital
      • Ramat Gan, Israel, 5265601
        • Chaim Sheba Medical Center
      • Tel Aviv, Israel, 64239
        • Tel-Aviv Sourasky Medical Center
  • Italy
      • Bologna, Italy, 40139
        • Ospedale Bellaria
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Neurologico Carlo Besta
      • Naples, Italy, 80147
        • Ospedale del Mare
      • Padova, Italy, 35128
        • UOC Oncologia Medica 1 Istituto Oncologico Veneto IOV-IRCCS
      • Rozzano, Italy, 20089
        • IRCCS Istituto Clinico Humanitas
      • Siena, Italy, 53100
        • U.O.C. Immunoterapia Oncologica A.O.U. Senese, Policlinico Santa Maria alle Scotte
    • Torino
      • Torino, Torino, Italy, 10126
        • Neuro-Oncologia Clinica Ospedale Molinette - AOU Città della Salute e della Scienza di Torino
  • Japan
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
      • Hokkaido, Japan, 060-8648
        • Hokkaido University Hospital
      • Ishikawa, Japan, 920-8641
        • Kanazawa University Hospital
      • Kumamoto, Japan, 860-8556
        • Kumamoto University Hospital
      • Kyoto, Japan, 606-8507
        • Kyoto University Hospital
      • Mitaka, Japan, 181-8611
        • Kyorin University Hospital
      • Nagoya, Japan, 466-8560
        • Nagoya University Hospital
      • Saitama, Japan, 350-1298
        • Saitama Medical University International Medical Center
      • Sendai, Japan, 980-8574
        • Tohoku University Hospital
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
    • Aichi-ken
      • Toyoake-shi, Aichi-ken, Japan, 470-1192
        • Fujita Health University Hospital
    • Kanagawa
      • Isehara, Kanagawa, Japan, 259-1193
        • Tokai University Hospital
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Centrum Onkologii
      • Gliwice, Poland, 44-102
        • Narodowy Instytut Onkologii
      • Lodz, Poland, 93-513
        • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika-Zakład Teleradioterapii
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08908
        • Institut Català d'Oncologia de L'Hospitalet (ICO L'Hospitalet)
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de las Nieves
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46026
        • Hospital Universitari i Politécnic La Fe
    • Madrid
      • Madrid, Madrid, Spain, 28040
        • Hospital Universitario Clínico San Carlos
  • Switzerland
      • Basel, Switzerland, 4031
        • University Hospital Basel Medical Oncology
      • Lausanne, Switzerland, 1005
        • Centre Hospitalier Universitaire Vaudois (CHUV)
      • Zurich, Switzerland, 8091
        • University Hospital Zurich
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Queen Elizabeth
      • Cambridge, United Kingdom, CB2 0QQ
        • Addenbrooke's Hospital (Cambridge University Hospitals NHS Foundation Trust)
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
      • Edinburgh, United Kingdom, EH4 2XU
        • Western General Hospital
      • Liverpool, United Kingdom, L7 8YA
        • The Clatterbridge Cancer Centre (Clatterbridge Cancer Centre NHS Foundation Trust)
      • Manchester, United Kingdom, M20 4BX
        • The Christie Hospital
      • Sheffield, United Kingdom, S10 2SJ
        • Weston Park Hospital
      • Southampton, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Sutton, United Kingdom, SM2 5PT
        • Royal Marsden
    • Greater London
      • London, Greater London, United Kingdom, W6 8RF
        • Charing Cross Hospital
    • Middlesex
      • Northwood, Middlesex, United Kingdom, HA6 2RN
        • Mount Vernon Cancer Centre
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California
      • Newport Beach, California, United States, 92663
        • Hoag Memorial Hospital Presbyterian
      • Palo Alto, California, United States, 94305
        • Stanford Cancer Institute
      • San Francisco, California, United States, 94143
        • University of California
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • MedStar Georgetown University Hospital
    • Florida
      • Gainesville, Florida, United States, 32608
        • UF Health Neuromedicine
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - Florida
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Medical Center
      • Louisville, Kentucky, United States, 40241
        • Norton Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University
    • Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center/ Hackensack Meridian Health
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Cancer Institute of New Jersey University Hospital
    • New York
      • Lake Success, New York, United States, 11042
        • Northwell Health
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center- Montefiore Medical Park
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Institute
      • Cleveland, Ohio, United States, 44195
        • The Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Clinical Trials Organization
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas
      • Houston, Texas, United States, 77030
        • University of Texas, MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute, University of Utah
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98122
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NovoCure GmbH

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 3, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 13, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 16, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

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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