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

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).

Interventions

• Optune® device · DEVICE

  Optune® device delivering TTFields therapy at 200 kHz.

• Temozolomide · DRUG

  Temozolomide per approved labeling.

• Pembrolizumab · DRUG

  Pembrolizumab dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles.

• Placebo · DRUG

  Placebo (saline solution) dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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.

Sites (102)

• Mayo Clinic Hospital, Phoenix, Arizona · Active, not recruiting
• University of Southern California, Los Angeles, California · Active, not recruiting
• Hoag Memorial Hospital Presbyterian, Newport Beach, California · Active, not recruiting
• Stanford Cancer Institute, Palo Alto, California · Active, not recruiting
• University of California, San Francisco, California · Active, not recruiting
• MedStar Georgetown University Hospital, Washington D.C., District of Columbia · Active, not recruiting
• UF Health Neuromedicine, Gainesville, Florida · Active, not recruiting
• Mayo Clinic - Florida, Jacksonville, Florida · Active, not recruiting
• Miami Cancer Institute, Miami, Florida · Active, not recruiting
• Moffitt Cancer Center, Tampa, Florida · Active, not recruiting
• Northwestern Memorial Hospital, Chicago, Illinois · Active, not recruiting
• University of Kentucky Medical Center, Lexington, Kentucky · Active, not recruiting
• Norton Cancer Institute, Louisville, Kentucky · Active, not recruiting
• University of Maryland, Baltimore, Maryland · Active, not recruiting
• Tufts Medical Center, Boston, Massachusetts · Active, not recruiting
• Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota · Active, not recruiting
• Mayo Clinic - Rochester, Rochester, Minnesota · Active, not recruiting
• Washington University, St Louis, Missouri · Active, not recruiting
• Renown Regional Medical Center, Reno, Nevada · Active, not recruiting
• John Theurer Cancer Center/ Hackensack Meridian Health, Hackensack, New Jersey · Active, not recruiting
• Rutgers Cancer Institute of New Jersey University Hospital, New Brunswick, New Jersey · Active, not recruiting
• Northwell Health, Lake Success, New York · Active, not recruiting
• Columbia University Irving Medical Center, New York, New York · Active, not recruiting
• Montefiore Medical Center- Montefiore Medical Park, The Bronx, New York · Active, not recruiting
• Duke University Medical Center, Durham, North Carolina · Active, not recruiting
• University of Cincinnati Cancer Institute, Cincinnati, Ohio · Active, not recruiting
• University Hospitals Cleveland Medical Center, Cleveland, Ohio · Active, not recruiting
• The Cleveland Clinic, Cleveland, Ohio · Active, not recruiting
• Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Clinical Trials Organization, Philadelphia, Pennsylvania · Active, not recruiting
• UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania · Active, not recruiting
• Rhode Island Hospital, Providence, Rhode Island · Active, not recruiting
• The University of Texas, Houston, Texas · Active, not recruiting
• University of Texas, MD Anderson Cancer Center, Houston, Texas · Active, not recruiting
• Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah · Active, not recruiting
• Inova Schar Cancer Institute, Fairfax, Virginia · Active, not recruiting
• Swedish Medical Center, Seattle, Washington · Active, not recruiting
• Cross Cancer Institute, Edmonton, Alberta · Recruiting
• Hamilton Health Sciences-Juravinski Cancer Centre, Hamilton, Ontario · Recruiting
• The Ottawa Hospital Cancer Centre, Ottawa, Ontario · Recruiting
• University Health Network - Princess Margaret Cancer Centre, Toronto, Ontario · Recruiting
• CHUM, Montreal, Quebec · Recruiting
• Montreal Neurological Institute-Hospital, Clinical Research Unit, Montreal, Quebec · Recruiting
• Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie-CHUS), Sherbrooke, Quebec · Recruiting
• Nemocnice Na Homolce, Prague, Czechia · Active, not recruiting
• Centre Hospitalier Universitaire de Lyon, Bron, France · Active, not recruiting
• Hopital de la Timone, Marseille, France · Active, not recruiting
• Hopital Saint-Louis, Paris, France · Active, not recruiting
• Groupe Hospitalier Pitie - Salpetriere, Paris, France · Active, not recruiting
• Institut Claudius Regaud, Toulouse, France · Active, not recruiting
• Charité Campus Virchow-Klinikum, Berlin, Germany · Active, not recruiting
• Universitätsklinikum Essen, Essen, Germany · Active, not recruiting
• University Hospital Frankfurt, Frankfurt, Germany · Active, not recruiting
• Rambam Medical Center, Haifa, Israel · Active, not recruiting
• Rabin Medical Center- Beilinson Hospital, Petah Tikva, Israel · Active, not recruiting
• Chaim Sheba Medical Center, Ramat Gan, Israel · Active, not recruiting
• Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel · Active, not recruiting
• Neuro-Oncologia Clinica Ospedale Molinette - AOU Città della Salute e della Scienza di Torino, Torino, Torino · Active, not recruiting
• Ospedale Bellaria, Bologna, Italy · Active, not recruiting
• Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy · Active, not recruiting
• Ospedale del Mare, Naples, Italy · Active, not recruiting
• UOC Oncologia Medica 1 Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy · Active, not recruiting
• IRCCS Istituto Clinico Humanitas, Rozzano, Italy · Active, not recruiting
• U.O.C. Immunoterapia Oncologica A.O.U. Senese, Policlinico Santa Maria alle Scotte, Siena, Italy · Active, not recruiting
• Fujita Health University Hospital, Toyoake-shi, Aichi-ken · Recruiting
• Tokai University Hospital, Isehara, Kanagawa · Recruiting
• Kyushu University Hospital, Fukuoka, Japan · Recruiting
• Hokkaido University Hospital, Hokkaido, Japan · Recruiting
• Kanazawa University Hospital, Ishikawa, Japan · Recruiting
• Kumamoto University Hospital, Kumamoto, Japan · Recruiting
• Kyoto University Hospital, Kyoto, Japan · Recruiting
• Kyorin University Hospital, Mitaka, Japan · Recruiting
• Nagoya University Hospital, Nagoya, Japan · Recruiting
• Saitama Medical University International Medical Center, Saitama, Japan · Recruiting
• Tohoku University Hospital, Sendai, Japan · Recruiting
• National Cancer Center Hospital, Tokyo, Japan · Recruiting
• Centrum Onkologii, Bydgoszcz, Poland · Active, not recruiting
• Narodowy Instytut Onkologii, Gliwice, Poland · Active, not recruiting
• Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika-Zakład Teleradioterapii, Lodz, Poland · Active, not recruiting
• Hospital Universitario Clínico San Carlos, Madrid, Madrid · Active, not recruiting
• Hospital Universitari Vall d'Hebron, Barcelona, Spain · Active, not recruiting
• Institut Català d'Oncologia de L'Hospitalet (ICO L'Hospitalet), Barcelona, Spain · Active, not recruiting
• Hospital Universitario Reina Sofia, Córdoba, Spain · Active, not recruiting
• Hospital Universitario Virgen de las Nieves, Granada, Spain · Active, not recruiting
• Hospital Universitario Ramón y Cajal, Madrid, Spain · Active, not recruiting
• Hospital Universitario 12 de Octubre, Madrid, Spain · Active, not recruiting
• Hospital Universitario La Paz, Madrid, Spain · Active, not recruiting
• Hospital Universitario Virgen del Rocio, Seville, Spain · Active, not recruiting
• Hospital Universitari i Politécnic La Fe, Valencia, Spain · Active, not recruiting
• University Hospital Basel Medical Oncology, Basel, Switzerland · Active, not recruiting
• Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland · Active, not recruiting
• University Hospital Zurich, Zurich, Switzerland · Active, not recruiting
• Charing Cross Hospital, London, Greater London · Active, not recruiting
• Mount Vernon Cancer Centre, Northwood, Middlesex · Active, not recruiting
• Queen Elizabeth, Birmingham, United Kingdom · Active, not recruiting
• Addenbrooke's Hospital (Cambridge University Hospitals NHS Foundation Trust), Cambridge, United Kingdom · Active, not recruiting
• Velindre Cancer Centre, Cardiff, United Kingdom · Active, not recruiting
• Western General Hospital, Edinburgh, United Kingdom · Active, not recruiting
• The Clatterbridge Cancer Centre (Clatterbridge Cancer Centre NHS Foundation Trust), Liverpool, United Kingdom · Active, not recruiting
• The Christie Hospital, Manchester, United Kingdom · Active, not recruiting
• Weston Park Hospital, Sheffield, United Kingdom · Active, not recruiting
• Southampton General Hospital, Southampton, United Kingdom · Active, not recruiting
• Royal Marsden, Sutton, United Kingdom · Active, not recruiting