A study in newly diagnosed glioblastoma patients that aims at testing the efficacy of Optune (Tumor Treating Fields), together with temozolomide and pembrolizumab compared to Optune (Tumor Treating Fields), together with temozolomide, and placebo (ie. inactive substance)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novocure GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Mar 2025 → ongoing

Decision date (initial)

2025-02-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

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 objectives 7

1. 1. To evaluate progression-free survival (PFS) per response assessment in neuro-oncology criteria 2.0 (RANO 2.0) as assessed locally by the investigator for subjects treated with Optune concomitant with maintenance TMZ plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo
2. 2. To evaluate PFS per response assessment in neuro-oncology criteria (RANO) as assessed locally by the investigator for subjects treated with Optune concomitant with maintenance TMZ plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo
3. 3. To evaluate PFS rate at 6 months (PFS6m) and at 12 months (PFS12m) per RANO 2.0 as assessed locally by the investigator.
4. 4. To evaluate next PFS (PFS2) per RANO 2.0 as assessed locally by the investigator.
5. 5. To evaluate 1- and 2-year survival rates
6. 6. To evaluate changes in Health-Related Quality of Life (HRQoL) assessment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 with BN20 module
7. 7. To evaluate the severity and tolerability by the proportion of adverse events (AEs)

Conditions and MedDRA coding

Newly diagnosed Glioblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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

Exclusion criteria 22

1. 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).
2. 2. Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial mass effect.
3. 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.
4. 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
5. 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.
6. 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.
7. 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.
8. 8. Has severe hypersensitivity (≥Grade 3) to the experimental drug and/or any of its excipients.
9. 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.
10. 10. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
11. 11. Has an active infection requiring systemic therapy.
12. 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: - Known history of HBV and HCV infection - As mandated by local health authority
13. 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.
14. 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.
15. 15. Has had an allogenic tissue/solid organ transplant.
16. 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.
17. 17. Infratentorial or leptomeningeal disease.
18. 18. Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
19. 19. A skull defect (such as, missing bone with no replacement) or bullet fragments.
20. 20. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness).
21. 21. Known allergies to medical adhesives or hydrogel and/or compounds of similar chemical or biologic composition to Temozolomide.
22. 22. Admitted to an institution by administrative or court order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS

Secondary endpoints 7

1. 1. PFS per RANO 2.0 as assessed by investigator
2. 2. PFS per RANO as assessed by investigator
3. 3. PFS6m and PFS12m per RANO 2.0 as assessed by investigator
4. 4. PFS2 per RANO 2.0 as assessed by investigator
5. 5. 1- and 2-year survival rates
6. 6. The EORTC QLQ-C30 with BN20 module score
7. 7. Subjects experiencing AEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novocure GmbH

Sponsor organisation

Novocure GmbH

Address

Neuhofstrasse 21

City

Baar

Postcode

6340

Country

Switzerland

Scientific contact point

Organisation

Novocure GmbH

Contact name

Novocure Medical Information

Public contact point

Organisation

Novocure GmbH

Contact name

Novocure Medical Information

Third parties 7

Locations

6 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 138 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications