Clinical trial • Phase III • Oncology

PEMBROLIZUMAB for Glioblastoma

Phase III trial of PEMBROLIZUMAB for Glioblastoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Glioblastoma
Trial Stage
Phase III
Drug Modality
Small molecule|Monoclonal antibody

Key dates

Initial CTIS Submission Date
26-07-2024
First CTIS Authorization Date
27-01-2025

Trial design

Randomised, optune concomitant with maintenance temozolomide (150-200 mg/m^2 daily x 5, q28 days) plus pembrolizumab versus optune concomitant with maintenance temozolomide (150-200 mg/m^2 daily x 5, q28 days) plus placebo (saline solution for infusion). pembrolizumab product: keytruda 25 mg/ml concentrate for solution for infusion. placebo: saline solution for infusion.-controlled Phase III trial in Poland, France, Spain and others.

Randomised
Yes
Comparator
Optune concomitant with maintenance temozolomide (150-200 mg/m^2 daily x 5, Q28 days) plus pembrolizumab versus Optune concomitant with maintenance temozolomide (150-200 mg/m^2 daily x 5, Q28 days) plus placebo (saline solution for infusion). Pembrolizumab product: KEYTRUDA 25 mg/mL concentrate for solution for infusion. Placebo: saline solution for infusion.
Target Sample Size
461
Trial Duration For Participant
730

Eligibility

Recruits 461 Vulnerable population selected; consent must be documented and may be provided by the participant or a legally acceptable representative ("The participant (or legally acceptable representative) has provided documented informed consent for the study."). No assent for minors is applicable since participants must be ≥ 18 years of age..

Vulnerable Population
Vulnerable population selected; consent must be documented and may be provided by the participant or a legally acceptable representative ("The participant (or legally acceptable representative) has provided documented informed consent for the study."). No assent for minors is applicable since participants must be ≥ 18 years of age.

Inclusion criteria

  • {"criterion_text":"- 1. The participant (or legally acceptable representative) has provided documented informed consent for the study.\n- 10. Life expectancy ≥ 3 months.\n- 11. Stable or decreasing dose of corticosteroids (dexamethasone ≤ 2mg or equivalent) for the last 7 days prior to randomization, if applicable.\n- 12. For the full list of inclusion criteria, please refer to the protocol.\n- 2. Be ≥ 18 years of age on day of providing informed consent.\n- 3. Participant with new diagnosis of GBM according to WHO 2021 Classification.\n- 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.\n- 5. Have completed standard adjuvant chemoradiotherapy of RT according to local practice (56-64 Gy), and concomitant TMZ chemotherapy.\n- 6. Able to start treatment between 4 to 7 weeks from the later of last dose of concomitant temozolomide or radiotherapy.\n- 7. Amenable to treatment with Optune concomitant with maintenance temozolomide (150-200 mg/m^2 daily x 5, Q28 days).\n- 8. All patients must have had tissue submitted for MGMT Promoter Methylation determination prior to randomization.\n- 9. Have an ECOG Performance Status of 0 to 1 assessed within 7 days before randomization."}

Exclusion criteria

  • {"criterion_text":"- 1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).\n- 10. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.\n- 11. Has an active infection requiring systemic therapy.\n- 12. Has a known history of human immunodeficiency virus (HIV), Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection Note: Hepatitis B and C screening tests are not required unless: \t- Known history of HBV and HCV infection \t- As mandated by local health authority\n- 13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.\n- 14. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.\n- 15. Has had an allogenic tissue/solid organ transplant.\n- 16. Early progressive disease after the end of TMZ/RT. If pseudoprogression is suspected, additional imaging studies should be performed to rule out true progression.\n- 17. Infratentorial or leptomeningeal disease.\n- 18. Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.\n- 19. A skull defect (such as, missing bone with no replacement) or bullet fragments.\n- 2. Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial mass effect.\n- 20. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness).\n- 21. Known allergies to medical adhesives or hydrogel and/or compounds of similar chemical or biologic composition to Temozolomide.\n- 22. Admitted to an institution by administrative or court order.\n- 3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible. Note: If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention.\n- 4. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to Section 6.5.1 for information on COVID-19 vaccines\n- 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. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.\n- 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.\n- 7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.\n- 8. Has severe hypersensitivity (≥Grade 3) to the experimental drug and/or any of its excipients.\n- 9. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- OS","definition_or_measurement_approach":"To compare overall survival (OS) for subjects treated with Optune concomitant with maintenance temozolomide (TMZ) plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo"}

Secondary endpoints

  • {"endpoint_text":"- 1. PFS per RANO 2.0 as assessed by investigator","definition_or_measurement_approach":"Progression-free survival per response assessment in neuro-oncology criteria 2.0 (RANO 2.0) as assessed locally by the investigator"}
  • {"endpoint_text":"- 2. PFS per RANO as assessed by investigator","definition_or_measurement_approach":"Progression-free survival per response assessment in neuro-oncology criteria (RANO) as assessed locally by the investigator"}
  • {"endpoint_text":"- 3. PFS6m and PFS12m per RANO 2.0 as assessed by investigator","definition_or_measurement_approach":"PFS rate at 6 months and 12 months per RANO 2.0 as assessed locally by the investigator"}
  • {"endpoint_text":"- 4. PFS2 per RANO 2.0 as assessed by investigator","definition_or_measurement_approach":"Next progression-free survival (PFS2) per RANO 2.0 as assessed locally by the investigator"}
  • {"endpoint_text":"- 5. 1- and 2-year survival rates","definition_or_measurement_approach":"Proportion of subjects alive at 1 year and 2 years"}
  • {"endpoint_text":"- 6. The EORTC QLQ-C30 with BN20 module score","definition_or_measurement_approach":"Health-Related Quality of Life assessment using EORTC QLQ-C30 with BN20 brain module scores"}
  • {"endpoint_text":"- 7. Subjects experiencing AEs","definition_or_measurement_approach":"Safety assessed by proportion and severity of adverse events (AEs)"}

Recruitment

Digital Remote Recruitment
True, recruitment materials include website text and online/media kit materials; eCOA and online patient-facing documents are provided for electronic capture and subject interaction
Planned Sample Size
461
Recruitment Window Months
41
Consent Approach
Documented informed consent is required from the participant or a legally acceptable representative ("The participant (or legally acceptable representative) has provided documented informed consent for the study."). Participants must be ≥18 years old. Informed consent and subject information documents are available in multiple languages (document titles indicate availability in EN, FR, ES, IT, PL, CZ, DE and country-specific versions).

Methods

  • Website text / online information (documents titled 'Website Text' / country-specific Website Text documents) for public-facing recruitment information
  • Media kit / advertisement materials (documents titled 'Media Kit' / 'Advertisement material') for outreach
  • Referral letters and GP letters (documents titled 'Referral Letter', 'GP Letter') to engage referring physicians
  • Participant-facing materials and patient information sheets (multiple Subject Information Sheet and ICF documents) provided at sites
  • Printed recruitment materials and patient diaries (Media Kit, Patient Diary, Patient Card, Flyers) for site distribution

Geography

Total Number Of Sites
32
Total Number Of Participants
280

Poland

Earliest CTIS Part Ii Submission Date
19-02-2025
Latest Decision Or Authorization Date
30-11-2025
Processing Time Days
284
Number Of Sites
3
Number Of Participants
21

Sites

Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Zakład Teleradioterapii
Principal Investigator Name
Jacek Fijuth
Principal Investigator Email
jacekf@kopernik.lodz.pl
Contact Person Name
Jacek Fijuth
Contact Person Email
jacekf@kopernik.lodz.pl
Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Zakład Neuroonkologii i Radiochirurgii
Principal Investigator Name
Maciej Harat
Principal Investigator Email
haratm@co.bydgoszcz.pl
Contact Person Name
Maciej Harat
Contact Person Email
haratm@co.bydgoszcz.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
III Klinika Radioterapii i Chemioterapii
Principal Investigator Name
Elżbieta Nowicka
Principal Investigator Email
elzbieta.nowicka@gliwice.nio.gov.pl
Contact Person Name
Elżbieta Nowicka

France

Earliest CTIS Part Ii Submission Date
27-01-2025
Latest Decision Or Authorization Date
25-11-2025
Processing Time Days
302
Number Of Sites
5
Number Of Participants
55

Sites

Site Name
Centre Hospitalier Regional De Marseille
Department Name
Marseille Center of Earlier Phase in Oncology
Principal Investigator Name
Emeline Tabouret
Principal Investigator Email
emeline.tabouret@ap-hm.fr
Contact Person Name
Emeline Tabouret
Contact Person Email
emeline.tabouret@ap-hm.fr
Site Name
Hospices Civils De Lyon
Department Name
Neuro-Oncology
Principal Investigator Name
François Ducray
Principal Investigator Email
francois.ducray@chu-lyon.fr
Contact Person Name
François Ducray
Contact Person Email
francois.ducray@chu-lyon.fr
Site Name
Oncopole Claudius Regaud
Department Name
Radiotherapy
Principal Investigator Name
Elizabeth Moyal
Principal Investigator Email
moyal.elizabeth@iuct-oncopole.fr
Contact Person Name
Elizabeth Moyal
Site Name
Hopital Saint Louis
Department Name
Neurology
Principal Investigator Name
Stephania Cuzzubo
Principal Investigator Email
stefania.cuzzubbo@aphp.fr
Contact Person Name
Stephania Cuzzubo
Contact Person Email
stefania.cuzzubbo@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Neurology
Principal Investigator Name
Khe Hoang-Xuan
Principal Investigator Email
khe.hoang-xuan@aphp.fr
Contact Person Name
Khe Hoang-Xuan
Contact Person Email
khe.hoang-xuan@aphp.fr

Spain

Earliest CTIS Part Ii Submission Date
29-01-2025
Latest Decision Or Authorization Date
26-11-2025
Processing Time Days
301
Number Of Sites
10
Number Of Participants
71

Sites

Site Name
Hospital Universitario La Paz
Department Name
Oncology
Principal Investigator Name
Virginia Martinez Marin
Principal Investigator Email
virgimarin9@hotmail.com
Contact Person Name
Virginia Martinez Marin
Contact Person Email
virgimarin9@hotmail.com
Site Name
Hospital Universitario Virgen De Las Nieves
Department Name
Oncology
Principal Investigator Name
Raquel Luque Caro
Principal Investigator Email
rluquecaro@gmail.com
Contact Person Name
Raquel Luque Caro
Contact Person Email
rluquecaro@gmail.com
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Oncology
Principal Investigator Name
Maria Angeles Vaz Salgado
Principal Investigator Email
mavaz4@gmail.com
Contact Person Name
Maria Angeles Vaz Salgado
Contact Person Email
mavaz4@gmail.com
Site Name
Hospital Clinico San Carlos
Department Name
Oncology
Principal Investigator Name
Pedro Perez Segura
Principal Investigator Email
pedro.perez@salud.madrid.org
Contact Person Name
Pedro Perez Segura
Contact Person Email
pedro.perez@salud.madrid.org
Site Name
ICO L'HOSPITALET HOSPITAL DURAN I REYNALS
Department Name
Neurology
Principal Investigator Name
Jordi Bruna Escuer
Principal Investigator Email
miguelamosteiro@iconcologia.net
Contact Person Name
Jordi Bruna Escuer
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Oncology
Principal Investigator Name
Regina Girones Sarrio
Principal Investigator Email
girones_reg@gva.es
Contact Person Name
Regina Girones Sarrio
Contact Person Email
girones_reg@gva.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Oncology
Principal Investigator Name
Miriam Alonso Garcia
Principal Investigator Email
miriamag3@hotmail.com
Contact Person Name
Miriam Alonso Garcia
Contact Person Email
miriamag3@hotmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Principal Investigator Name
Maria Vieito Villar
Principal Investigator Email
mvieito@vhio.net
Contact Person Name
Maria Vieito Villar
Contact Person Email
mvieito@vhio.net
Site Name
Hospital Universitario Reina Sofia
Department Name
Oncology
Principal Investigator Name
Raquel Serrano Blanch
Principal Investigator Email
rsblanch@hotmail.com
Contact Person Name
Raquel Serrano Blanch
Contact Person Email
rsblanch@hotmail.com
Site Name
Hospital Universitario 12 De Octubre
Department Name
Neuro-Oncology
Principal Investigator Name
Juan Manuel Sepulveda Sanchez
Principal Investigator Email
jmsepulveda76@gmail.com
Contact Person Name
Juan Manuel Sepulveda Sanchez
Contact Person Email
jmsepulveda76@gmail.com

Czechia

Earliest CTIS Part Ii Submission Date
30-01-2025
Latest Decision Or Authorization Date
25-11-2025
Processing Time Days
299
Number Of Sites
1
Number Of Participants
20

Sites

Site Name
Nemocnice Na Homolce
Department Name
Radiodiagnosticke oddeleni
Principal Investigator Name
Josef Vymazal
Principal Investigator Email
josef.vymazal@homolka.cz
Contact Person Name
Josef Vymazal
Contact Person Email
josef.vymazal@homolka.cz

Germany

Earliest CTIS Part Ii Submission Date
20-02-2025
Latest Decision Or Authorization Date
28-11-2025
Processing Time Days
281
Number Of Sites
4
Number Of Participants
35

Sites

Site Name
Universitaetsklinikum Muenster AöR
Department Name
department of Neurology with Institute of Translational Neurology
Principal Investigator Name
Oliver Grauer
Principal Investigator Email
oliver.grauer@ukmuenster.de
Contact Person Name
Oliver Grauer
Contact Person Email
oliver.grauer@ukmuenster.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
department of Neurosurgery
Principal Investigator Name
Martin Misch
Principal Investigator Email
martin.misch@charite.de
Contact Person Name
Martin Misch
Contact Person Email
martin.misch@charite.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
department of Neurology
Principal Investigator Name
Sied Kebir
Principal Investigator Email
sied.kebir@uk-essen.de
Contact Person Name
Sied Kebir
Contact Person Email
sied.kebir@uk-essen.de
Site Name
Goethe University Frankfurt
Department Name
department for Neurology and Neurosurgery
Principal Investigator Name
Michael Burger
Principal Investigator Email
burger@med.uni-frankfurt.de
Contact Person Name
Michael Burger
Contact Person Email
burger@med.uni-frankfurt.de

Italy

Earliest CTIS Part Ii Submission Date
21-06-2024
Latest Decision Or Authorization Date
02-02-2026
Processing Time Days
591
Number Of Sites
9
Number Of Participants
78

Sites

Site Name
Azienda Unita Sanitaria Locale Di Bologna
Department Name
Oncologia
Principal Investigator Name
Enrico Franceschi
Principal Investigator Email
e.franceschi@isnb.it
Contact Person Name
Enrico Franceschi
Contact Person Email
e.franceschi@isnb.it
Site Name
Azienda Sanitaria Locale Napoli 1 Centro
Department Name
Oncology
Principal Investigator Name
Bruno Daniele
Principal Investigator Email
bruno.daniele@aslnapoli1centro.it
Contact Person Name
Bruno Daniele
Site Name
Humanitas Mirasole S.p.A.
Department Name
Operating Unit of Oncology and Hematology
Principal Investigator Name
Matteo Simonelli
Principal Investigator Email
matteo.simonelli@cancercenter.humanitas.it
Contact Person Name
Matteo Simonelli
Site Name
IRCCS Foundation Istituto Neurologico Carlo Besta
Department Name
Neuro-oncologia
Principal Investigator Name
Antonio Silvani
Principal Investigator Email
antonio.silvani@istituto-besta.it
Contact Person Name
Antonio Silvani
Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
UOC Immunoterapia oncologica
Principal Investigator Name
Michele Maio
Principal Investigator Email
mmaiocro@gmail.com
Contact Person Name
Michele Maio
Contact Person Email
mmaiocro@gmail.com
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Radiation Therapy
Principal Investigator Name
Silvia Chiesa
Principal Investigator Email
silvia.chiesa@policlinicogemelli.it
Contact Person Name
Silvia Chiesa
Site Name
Istituto Oncologico Veneto
Department Name
Oncology 1 Unit
Principal Investigator Name
Giuseppe Lombardi
Principal Investigator Email
giuseppe.lombardi@iov.veneto.it
Contact Person Name
Giuseppe Lombardi
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
Neuro-oncology
Principal Investigator Name
Roberta Rudà
Principal Investigator Email
roberta.ruda@unito.it
Contact Person Name
Roberta Rudà
Contact Person Email
roberta.ruda@unito.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino (additional listing)

Sponsor

Primary sponsor

Full Name
Novocure GmbH
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Almac Clinical Services Limited
Responsibilities
Drug Product Secondary Production, Storage, Distribution, Returns and Destruction
Name
IQVIA Limited
Responsibilities
roles/codes: 1,11,12,2,5,6,8 (as listed in sponsor thirdParty duties)
Name
Q Squared Solutions Limited
Responsibilities
code: 4 (as listed in sponsor thirdParty duties)
Name
Medidata Solutions Inc.
Responsibilities
roles/codes: 3,7 (as listed in sponsor thirdParty duties)
Name
Bioclinica Inc.
Responsibilities
Imaging
Name
Mayo Collaborative Services LLC
Responsibilities
MGMT analysis

Third parties

  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Drug Product Secondary Production, Storage, Distribution, Returns and Destruction","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 1,11,12,2,5,6,8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"MGMT analysis; code: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging; code: 13","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes: 3,7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Drug Product Storage, Distribution, Returns and Destruction for Switzerland sites","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
KEYTRUDA 25 mg/mL concentrate for solution for infusion
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Marketing authorisation: EU/1/15/1024/002
Maximum Dose
200 mg (maxDailyDoseAmount 200 mg)
Investigational Product Name
TEMOZOLOMIDE
Active Substance
TEMOZOLOMIDE
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
EU product (euMpNumber SCP131007)
Starting Dose
150-200 mg/m^2 daily x 5, Q28 days (maintenance dosing as stated in protocol inclusion)
Dose Levels
150-200 mg/m^2 daily x 5, Q28 days
Frequency
Daily x 5 every 28 days
Maximum Dose
200 mg/m2 (maxDailyDoseAmount 200)
Investigational Product Name
saline solution for infusion
Modality
Other
Routes Of Administration
Intravenous (placebo)
Route
Intravenous infusion
Combination Treatment
Yes

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