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

Official title

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).

Overview

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).

Interventions

• Device Optune® device
  Optune® device delivering TTFields therapy at 200 kHz.
• Drug Temozolomide
  Temozolomide per approved labeling.
• Drug Pembrolizumab
  Pembrolizumab dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles.
• Drug Placebo
  Placebo (saline solution) dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles.

Primary outcome measures

• Overall survival [Time frame: 24 months]

Secondary outcome measures (2)

• Progression-Free Survival (PFS) per RANO 2.0 assessed by investigator [Time frame: 24 months]
• Progression-Free Survival (PFS) per RANO 2.0 assessed by investigator [Time frame: 24 months]

Eligibility criteria

Inclusion criteria

• The participant (or legally acceptable representative) has provided documented informed consent for the study.
• Be ≥ 18 years of age on day of providing informed consent.
• Participant with new diagnosis of GBM according to World Health Organization (WHO) 2021 Classification.
• 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.
• Have completed standard adjuvant chemoradiotherapy of radiotherapy (RT) according to local practice (56-64 Gy), and concomitant TMZ chemotherapy.
• Amenable to treatment with Optune concomitant with maintenance TMZ (150-200 mg/m\^2 daily x 5, Q28 days).
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days before randomization.
• Stable or decreasing dose of corticosteroids (dexamethasone ≤ 2mg or equivalent) for the last 7 days prior to randomization, if applicable.

Exclusion criteria

• 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).
• Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial mass effect.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
• 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.
• 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.
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• 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.
• Infratentorial or leptomeningeal disease.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 36 centers

• Mayo Clinic Hospital — Phoenix
• University of Southern California — Los Angeles
• Hoag Memorial Hospital Presbyterian — Newport Beach
• Stanford Cancer Institute — Palo Alto
• University of California — San Francisco
• MedStar Georgetown University Hospital — Washington D.C.
• UF Health Neuromedicine — Gainesville
• Mayo Clinic - Florida — Jacksonville
• … and 28 more centers

Japan · 12 centers

• Fujita Health University Hospital — Toyoake-shi
• Tokai University Hospital — Isehara
• Kyushu University Hospital — Fukuoka
• Hokkaido University Hospital — Hokkaido
• Kanazawa University Hospital — Ishikawa
• Kumamoto University Hospital — Kumamoto
• Kyoto University Hospital — Kyoto
• Kyorin University Hospital — Mitaka
• … and 4 more centers

United Kingdom · 11 centers

Center list to be confirmed — check the primary protocol.

Spain · 10 centers

• Hospital Universitario Clínico San Carlos — Madrid
• Hospital Universitari Vall d'Hebron — Barcelona
• … and 8 more centers

Canada · 7 centers

• Cross Cancer Institute — Edmonton
• Hamilton Health Sciences-Juravinski Cancer Centre — Hamilton
• The Ottawa Hospital Cancer Centre — Ottawa
• University Health Network - Princess Margaret Cancer Centre — Toronto
• CHUM — Montreal
• Montreal Neurological Institute-Hospital, Clinical Research Unit — Montreal
• Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospital — Sherbrooke

Italy · 7 centers

• Neuro-Oncologia Clinica Ospedale Molinette - AOU Città della Salute e della Scienza di Tor — Torino
• Ospedale Bellaria — Bologna
• Fondazione IRCCS Istituto Neurologico Carlo Besta — Milan
• Ospedale del Mare — Naples
• UOC Oncologia Medica 1 Istituto Oncologico Veneto IOV-IRCCS — Padova
• IRCCS Istituto Clinico Humanitas — Rozzano
• U.O.C. Immunoterapia Oncologica A.O.U. Senese, Policlinico Santa Maria alle Scotte — Siena

France · 5 centers

• Centre Hospitalier Universitaire de Lyon — Bron
• Hopital de la Timone — Marseille
• Hopital Saint-Louis — Paris
• Groupe Hospitalier Pitie - Salpetriere — Paris
• Institut Claudius Regaud — Toulouse

Israel · 4 centers

• Rambam Medical Center — Haifa
• Rabin Medical Center- Beilinson Hospital — Petah Tikva
• Chaim Sheba Medical Center — Ramat Gan
• Tel-Aviv Sourasky Medical Center — Tel Aviv

Germany · 3 centers

• Charité Campus Virchow-Klinikum — Berlin
• Universitätsklinikum Essen — Essen
• University Hospital Frankfurt — Frankfurt

Poland · 3 centers

• Centrum Onkologii — Bydgoszcz
• Narodowy Instytut Onkologii — Gliwice
• Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika-Zakład — Lodz

Switzerland · 3 centers

Center list to be confirmed — check the primary protocol.

Czechia · 1 center

• Nemocnice Na Homolce — Prague

Identifiers

NCT: NCT06556563 · EF-41 · 2024-513550-30-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗