Clinical trial NCT06556563: 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).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Glioblastoma
Keywords: TTFields
Pembrolizumab
Glioblastoma
Tumor Treating Fields
Immunotherapy
Merck Sharp & Dohme LLC
GBM
Lead sponsor: NovoCure Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-08-16
Enrollment: 741
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants in the study will be randomized in a ratio of 2:1 in favor of the treatment group to one of the following groups:

Treatment Group - Optune concomitant with maintenance TMZ and pembrolizumab.

Control Group - Optune concomitant with maintenance TMZ and placebo.
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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 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.

Primary outcomes:
measure: Overall survival
timeFrame: 24 months
Secondary outcomes:
measure: Progression-Free Survival (PFS) per mRANO assessed by investigator
timeFrame: 24 months
measure: Progression-Free Survival (PFS) per RANO assessed by investigator
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Gainesville
country: United States
facility: UF Health Neuromedicine
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center/ Hackensack Meridian Health
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center- Montefiore Medical Park
state: New York
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Clinical Trials Organization
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Groupe Hospitalier Pitie - Salpetriere
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Petah tikva
country: Israel
facility: Rabin Medical Center- Beilinson Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital (Cambridge University Hospitals NHS Foundation Trust)
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden
Study officials:
References: