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NCT06216301PHASE3Recruiting

LUNAR-2: TTFields With Pembrolizumab + Platinum-based Chemotherapy for Metastatic NSCLC

NovoCure GmbH

Start Date

7/31/2024

Completion Date

10/1/2028

Summary

This study, known as LUNAR-2, aims to investigate the effectiveness and safety of using TTFields, delivered by the NovoTTF-200T device, concomitantly administered with pembrolizumab and platinum-based chemotherapy for patients with advanced non-small cell lung cancer that has spread to other parts of the body. The primary goals of the study are to assess overall survival and progression-free survival. Secondary objectives include analyzing outcomes based on the specific histology (subtype) of the lung cancer.

Detailed Description

LUNAR-2 is a pivotal, randomized, open-label study that aims to evaluate the effectiveness and safety of Tumor Treating Fields (TTFields) concomitantly administered with pembrolizumab and platinum-based chemotherapy for the treatment of metastatic non-small cell lung cancer (NSCLC). The primary objectives of the study are to assess overall survival (OS) and progression-free survival (PFS) in subjects treated with TTFields, pembrolizumab, and platinum-based chemotherapy compared to those treated with pembrolizumab and platinum-based chemotherapy alone. PFS will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The secondary endpoints of this study will evaluate PFS and OS, stratified by the specific histological subtype of NSCLC and PD-L1 Tumor Proportion Score (TPS). The population will consist of subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and will be stratified as follow: 1. Histology - Squamous vs. non-squamous 2. PD-L1 expression level - TPS \<1% vs. 1% ≤TPS \<50% vs. TPS ≥50% 3. Prior treatment with immunotherapy - yes vs. no The study will be conducted globally at approximately 130 participating sites. The study device, NovoTTF-200T, is a portable, battery-operated system that delivers TTFields at a frequency of 150kHz. It utilizes insulated transducer arrays to deliver electric forces intended to disrupt cancer cell division.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria * ≥22 years of age in the USA ≥18 years of age outside of the USA. * Histologically or cytologically diagnosis of stage 4 (according to Version 8 of the American Joint Committee on Cancer \[AJCC\] criteria) non-squamous or squamous NSCLC. * Evaluable (measurable or non-measurable) disease in the thorax per RECIST v1.1. * Have not received prior systemic treatment for their metastatic NSCLC. Subjects who received adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease are eligible if the therapy was completed at least 12 months prior to the development of metastatic disease. * ECOG Performance Status (PS) of 0-1. * Adequate hematologic and end-organ function o For subjects not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN (unless participant is receiving anticoagulant therapy as long as INR or aPTT is within therapeutic range of intended use of anticoagulants). * A female participant is eligible to participate if she is not pregnant, not breastfeeding * If male subject with a female partner(s) of child-bearing potential, must agree to use an effective contraception * All subjects must sign written informed consent. Exclusion Criteria: All individuals meeting any of the following exclusion criteria will be excluded from study participation: * Mixed small cell and NSCLC histology. * EGFR sensitizing mutation and/or ALK translocation, and/or ROS1 and/or RET targetable gene rearrangement, and/or METex14 skipping mutation, and/or NTRK1/2 gene fusion and/or BRAF V600 mutations directed therapy is indicated or planned for other targeted therapy, where such testing and therapy is locally approved and available. * Has received systemic therapy for metastatic disease. * Had major surgery \<3 weeks prior to randomization * Received radiation therapy to the lung that is \> 30 Gy within 6 months of randomization. * Has received prior radiotherapy within 2 weeks of randomization. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. * Is expected to require any other form of antineoplastic therapy while on study. * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. * Note: Subjects 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 * Has symptomatic Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Subjects with asymptomatic CNS metastases or with previously treated brain metastases may participate provided they were treated before randomization (if applicable) and are neurologically stable and without requirement of steroid treatment for at least 7 days prior to randomization. * Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). * 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 randomization. Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. * Had prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms in the 12 months prior to randomization. * Participation in another clinical study with an investigational agent or device during the 4 weeks prior to randomization. * Concurrent treatment with other experimental treatments for NSCLC while in the study. * Has a known sensitivity to any component of the planned systemic therapies (pembrolizumab, cisplatin/carboplatin, pemetrexed/paclitaxel/nab-paclitaxel) . * Pregnant or breastfeeding * Admitted to an institution by administrative or court order.

Interventions

DEVICE

NovoTTF-200T

DRUG

Pembrolizumab

DRUG

Platinum based chemotherapy

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Conditions

Metastatic Non-small Cell Lung Cancer

Locations

Central Alabama Research

Birmingham, Alabama 35209

United States

Western Regional Medical Center, LLC

Goodyear, Arizona 85338

United States

St. Jude Herritage Medical Group

Fullerton, California 92835

United States

Hoag Family Cancer Institute - Hoag Memorial Hospital

Newport Beach, California 92663

United States

Sutter Institute for Medical Research

Sacramento, California 95816

United States

Florida Cancer Affiliates - Ocala Oncology

Ocala, Florida 34474

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Northwest Oncology & Hematology

Barrington, Illinois 60010

United States

Elmhurst Hospital Nancy Knowles Cancer Center

Elmhurst, Illinois 60126

United States

Edward Cancer Center

Naperville, Illinois 60540-6766

United States

Cancer Treatment Centers of America (CTCA)

Zion, Illinois 60099

United States

Parkview Packnett Family Cancer Institute

Fort Wayne, Indiana 46845

United States

Franciscan Health Indianapolis

Indianapolis, Indiana 46237

United States

University of Kansas Cancer Center

Westwood, Kansas 66205

United States

Luminis Health Radiation Oncology - Anne Arundel Health System

Annapolis, Missouri 21401

United States

University of Kansas Cancer Center - North

Kansas City, Missouri 64154

United States

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri 64064

United States

University of Kansas Cancer Center - Overland Park

Overland, Missouri 66210

United States

New York Cancer & Blood Specialists (NYCBS)

New Hyde Park, New York 11042

United States

New York Cancer & Blood Specialists (NYCBS)

New York, New York 10028

United States

University of Rochester Medical Center

Rochester, New York 14642

United States

New York Cancer & Blood Specialists (NYCBS)

Shirley, New York 19967

United States

New York Cancer & Blood Specialists (NYCBS)

The Bronx, New York 10469

United States

WakeMed Health & Hospitals

Cary, North Carolina 27518

United States

Abramson Cancer Center

Philadelphia, Pennsylvania 19104

United States

AHN Cancer Center

Pittsburgh, Pennsylvania 15212

United States

Old Parkland Hospital Hematology Oncology Clinic

Dallas, Texas 75235

United States

UT Southwestern Medical Center

Dallas, Texas 75235

United States

DHR Health Oncology Institute

Edinburg, Texas 78539

United States

Houston Methodist Cancer Center

Houston, Texas 77030

United States

Methodist Richardson Cancer Center

Richardson, Texas 75082

United States

Jason Bates at University of Texas Health Science Center

San Antonio, Texas 78229

United States

MultiCare Regional Cancer Center

Auburn, Washington 98001

United States

MultiCare Regional Cancer Center

Gig Harbor, Washington 98335

United States

MultiCare Regional Cancer Center

Puyallup, Washington 98372

United States

MultiCare Deaconess Cancer and Blood Specialty Center - Downtown

Spokane, Washington 99218

United States

MultiCare Institute for Research & Innovation

Tacoma, Washington 98405

United States

Universitaetsklinik fuer Innere Medizin V Innsbruck

Innsbruck, 6020

Austria

University Hospital Salzburg

Salzburg, 5020

Austria

Karl Landsteiner Institut fur Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf

Vienna, 1210

Austria

Cliniques universitaires Saint-Luc

Brussels, 1200

Belgium

AZ Maria Middelares - Campus Maria Middelares

Ghent, 9000

Belgium

Fakultni nemocnice Olomouc FNOL

Olomouc, 779 00

Czechia

Nemocnice Agel Ostrava-Vitkovice / Agel Ostrava-Vitkovice Hospital

Ostrava, 70300

Czechia

General University Hospital in Prague

Prague, 12808

Czechia

Centre Hospitalier Intercommunal de Creteil

Créteil, 94010

France

CHU Limoges

Limoges, 87000

France

Hopital Europeen

Marseille, 13003

France

Hopital Prive du Confluent

Nantes, 44277

France

Institut Curie

Paris, 75005

France

CHU de Bordeaux

Pessac, 33604

France

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495

France

Nouvel Hopital Civil (NHC)

Strasbourg, 67091

France

Evangelische Lungenklinik Berlin

Berlin, 13125

Germany

University Hospital Giessen, ZIM IV

Giessen, 35392

Germany

Krankenhaus Martha-Maria Halle-Dolau

Halle, 06120

Germany

Thoraxklinik Heidelberg

Heidelberg, 69126

Germany

Klinik Loewenstein gGmbH

Löwenstein, 74245

Germany

Pius-Hospital Oldenburg

Oldenburg, 26121

Germany

Farkasgyepui Tudogyogyintezet

Farkasgyepű, 8582

Hungary

Bacs-Kiskun Varmegyei Oktatokorhaz

Kecskemét, 6000

Hungary

Tolna Varmegyei Balassa Janos Korhaz

Szekszárd, 7100

Hungary

Emek Medical Center

Afula, 1834111

Israel

Bnai zion MC

Haifa, 34561

Israel

A.O. SS. Antonio e Biagio e Cesare Arrigo di Alessandria

Alessandria, 15121

Italy

Humanitas Gavazzeni

Bergamo, 24125

Italy

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna

Ferrara, 44124

Italy

IRCCS - Istituto Romagnolo per lo Studio Dei Tumori, Dino Amadori

Meldola, 47014

Italy

Azienda Sanitaria Territoriale Pesaro Urbino

Pesaro, 61122

Italy

Universita Campus Bio-Medico di Roma (UCBM) - Policlinico Universitario

Roma, 00128

Italy

Ospedale Isola Tiberina Gemelli

Rome, 00186

Italy

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, 53100

Italy

Saitama Medical University International Medical Center

Hidaka, Saitama 350-1298

Japan

Rijnstate Ziekenhuis

Arnhem, 6815AD

Netherlands

Medisch Centrum Leeuwarden (MCL) - Oncologisch Centrum Leeuwarden (OCL)

Friesland, 8934 AD

Netherlands

St. Jansdal ziekenhuis

Harderwijk, 3844 DG

Netherlands

St Antonius Ziekenhuis

Utrecht, 3543 AZ

Netherlands

Uniwersytecki Szpital Kliniczny

Poznan, 60-693

Poland

NCCS Singapore

Singapore, 168583

Singapore

Curie Oncology

Singapore, 329563

Singapore

Icon Cancer Centre Singapore (Singapore Oncology Consultants)

Singapore, 574623

Singapore

Hospital Universitario del Vinalopo

Elche, Alicante 3293

Spain

Hospital Universitario Virgen del Rocio

Seville, Andalusia 41013

Spain

Clinica Mi Tres Torres Barcelona - Giromed Institute

Barcelona, Catalonia 8017

Spain

Hospital Universitario de Torrejon

Torrejón de Ardoz, Madrid 28850

Spain

Institut Catala d'Oncologia

Barcelona, 8916

Spain

Hospital Universitario Arnau de Vilanova

Lleida, 25198

Spain

Clinica Universidad de Navarra (Madrid)

Madrid, 28027

Spain

Hospital Ruber Internacional

Madrid, 28034

Spain

Hospital Regional Universitario de Malaga

Málaga, 29010

Spain

Clinica Universidad de Navarra

Pamplona, 31008

Spain

Cantonal Hospital Baden

Baden, 5404

Switzerland

HFR Freiburg-Kantonsspital

Fribourg, 1752

Switzerland

Charing Cross Hospital

London, Greater London

United Kingdom

University Hospitals of Leicester NHS Trust

Leicester, Leicestershire LE1 5WW

United Kingdom

The Royal Marsden NHS Foundation Trust

London, London SW3 6JJ

United Kingdom

Clatterbridge Cancer Centre - Liverpool

Liverpool, Merseyside L7 8YA

United Kingdom

The Royal Marsden NHS Foundation Trust - Sutton

Sutton, Sutton SM2 5PT

United Kingdom