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Combination treatment for newly diagnosed glioblastoma using Optune, Temozolomide, and Pembrolizumab

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).

Phase 3 Interventional NovoCure Ltd. · NCT06556563

This study is testing a new combination of treatments using a special device and two medications to see if it helps people with newly diagnosed glioblastoma live longer.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment741 (estimated)
Ages18 Years and up
SexAll
SponsorNovoCure Ltd. Industry-sponsored
Drugs / interventionschemotherapy, prednisone, pembrolizumab
Locations93 sites (Phoenix, Arizona and 92 other locations)
Trial IDNCT06556563 on ClinicalTrials.gov

What this trial studies

This phase 3 clinical trial evaluates the effectiveness of the Optune® device, which delivers Tumor Treating Fields, in combination with the chemotherapy agent Temozolomide and the immunotherapy Pembrolizumab in patients with newly diagnosed glioblastoma. The study is multicenter, randomized, and double-blind, comparing the active treatment group to a placebo group receiving the same regimen without Pembrolizumab. The primary goal is to assess overall survival among participants. Eligible patients must have recovered from surgery and completed standard adjuvant chemoradiotherapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a new diagnosis of glioblastoma who have completed initial treatment and are stable on corticosteroids.

Not a fit: Patients with advanced disease or those who have not recovered from surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could significantly improve survival rates for patients with newly diagnosed glioblastoma.

How similar studies have performed: Previous studies have shown promise with similar combinations of immunotherapy and chemotherapy in glioblastoma, but this specific approach is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Phoenix, Arizona and 92 other locations

+43 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions GlioblastomaTTFieldsPembrolizumabTumor Treating FieldsImmunotherapyMerck Sharp & Dohme LLCGBM
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.