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

Phase 3
Recruiting
Conditions
Metastatic Non-small Cell Lung Cancer
Interventions
Registration Number
NCT06216301
Lead Sponsor
NovoCure GmbH
Brief 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. TPS 1-49% 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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
734
Inclusion Criteria

Not provided

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 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 untreated or symptomatic Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they were treated before randomization and are clinically stable and without requirement of steroid treatment for at least 3 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1: NovoTTF-200T, Pembrolizumab, and Platinum-based ChemotherapyNovoTTF-200TSubjects in this arm receive three treatments - TTFields using the NovoTTF-200T device, pembrolizumab, and platinum-based chemotherapy.
Arm 1: NovoTTF-200T, Pembrolizumab, and Platinum-based ChemotherapyPlatinum based chemotherapySubjects in this arm receive three treatments - TTFields using the NovoTTF-200T device, pembrolizumab, and platinum-based chemotherapy.
Arm 2: Pembrolizumab and Platinum-based ChemotherapyPlatinum based chemotherapySubjects in this arm receive two treatments - pembrolizumab and platinum-based chemotherapy.
Arm 1: NovoTTF-200T, Pembrolizumab, and Platinum-based ChemotherapyPembrolizumabSubjects in this arm receive three treatments - TTFields using the NovoTTF-200T device, pembrolizumab, and platinum-based chemotherapy.
Arm 2: Pembrolizumab and Platinum-based ChemotherapyPembrolizumabSubjects in this arm receive two treatments - pembrolizumab and platinum-based chemotherapy.
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)up to 6 years

To compare OS in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy compared to OS of those treated with pembrolizumab and platinum-based chemotherapy alone (superiority analysis).

Progression Free Survival (PFS)up to 6 years

To compare PFS per RECIST v1.1 as assessed by BICR, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy compared to PFS of those treated with pembrolizumab and platinum-based chemotherapy alone (superiority analysis)

Secondary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR)up to 6 years

ORR per RECIST v1.1 as assessed by the investigator, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.

1, 2, and 3-year Survival Rateup to 6 years

1-, 2- and 3-year survival rate in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.

Adverse Eventsup to 6 years

Toxicity profile of TTFields concomitant with pembrolizumab and platinum-based chemotherapy. The analyses will be performed based on the incidence, severity, frequency of adverse events, and their association with study treatments.

Disease Control Rate (DCR)up to 6 years

DCR per RECIST v1.1 as assessed by the investigator, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.

Overall Survival (OS)up to 6 years

OS in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone according to PD-L1 TPS.

Duration of Response (DoR)up to 6 years

DoR per RECIST v1.1 as assessed by the investigator, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.

Progression Free Survival (PFS)up to 6 years

PFS per RECIST v1.1 as assessed by the investigator, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.

Trial Locations

Locations (50)

Central Alabama Research

🇺🇸

Birmingham, Alabama, United States

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

🇦🇹

Vienna, Austria

Cliniques universitaires Saint-Luc

🇧🇪

Brussels, Belgium

AZ Maria Middelares - Campus Maria Middelares

🇧🇪

Gent, Belgium

Fakultni nemocnice Olomouc FNOL

🇨🇿

Olomouc, Czechia

Nemocnice Agel Ostrava-Vitkovice / Agel Ostrava-Vitkovice Hospital

🇨🇿

Ostrava, Czechia

Farkasgyepui Tudogyogyintezet

🇭🇺

Farkasgyepu, Hungary

Tolna Varmegyei Balassa Janos Korhaz

🇭🇺

Szekszárd, Hungary

Emek Medical Center

🇮🇱

Afula, Israel

Bnai zion MC

🇮🇱

Haifa, Israel

Humanitas Gavazzeni

🇮🇹

Bergamo, Italy

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

🇮🇹

Siena, Italy

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

🇳🇱

Friesland, Netherlands

St. Jansdal ziekenhuis

🇳🇱

Harderwijk, Netherlands

St Antonius Ziekenhuis

🇳🇱

Utrecht, Netherlands

NCCS Singapore

🇸🇬

Singapore, Singapore

Curie Oncology

🇸🇬

Singapore, Singapore

Icon Cancer Centre Singapore (Singapore Oncology Consultants)

🇸🇬

Singapore, Singapore

Hospital Universitario del Vinalopo

🇪🇸

Elche, Alicante, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Andalucia, Spain

Clinica Mi Tres Torres Barcelona - Giromed Institute

🇪🇸

Barcelona, Cataluna, Spain

Hospital Universitario de Torrejon

🇪🇸

Torrejón De Ardoz, Madrid, Spain

Hospital Universitario Arnau de Vilanova

🇪🇸

Lleida, Spain

Hospital Ruber Internacional

🇪🇸

Madrid, Spain

Hospital Regional Universitario de Malaga

🇪🇸

Málaga, Spain

Kantonsspital Baden

🇨🇭

Baden, Switzerland

Universitaetsklinik fuer Innere Medizin V Innsbruck

🇦🇹

Innsbruck, Austria

University Hospital Salzburg

🇦🇹

Salzburg, Austria

Western Regional Medical Center, LLC

🇺🇸

Goodyear, Arizona, United States

St. Jude Herritage Medical Group

🇺🇸

Fullerton, California, United States

Hoag Family Cancer Institute - Hoag Memorial Hospital

🇺🇸

Newport Beach, California, United States

Sutter Institute for Medical Research

🇺🇸

Sacramento, California, United States

Florida Cancer Affiliates - Ocala Oncology

🇺🇸

Ocala, Florida, United States

BRCR Global

🇺🇸

Plantation, Florida, United States

Northwest Oncology & Hematology

🇺🇸

Barrington, Illinois, United States

Elmhurst Hospital Nancy Knowles Cancer Center

🇺🇸

Elmhurst, Illinois, United States

Edward Cancer Center

🇺🇸

Naperville, Illinois, United States

Edward Cancer Center-Plainfield

🇺🇸

Plainfield, Illinois, United States

Cancer Treatment Centers of America (CTCA)

🇺🇸

Zion, Illinois, United States

Franciscan Health Indianapolis

🇺🇸

Indianapolis, Indiana, United States

University of Kansas Cancer Center

🇺🇸

Westwood, Kansas, United States

University of Kansas Cancer Center - North

🇺🇸

Kansas City, Missouri, United States

University of Kansas Cancer Center - Lee's Summit

🇺🇸

Lee's Summit, Missouri, United States

University of Kansas Cancer Center - Overland Park

🇺🇸

Overland, Missouri, United States

New York Cancer & Blood Specialists (NYCBS)

🇺🇸

Shirley, New York, United States

WakeMed Health & Hospitals

🇺🇸

Cary, North Carolina, United States

DHR Health Oncology Institute

🇺🇸

Edinburg, Texas, United States

MultiCare Regional Cancer Center

🇺🇸

Puyallup, Washington, United States

MultiCare Deaconess Cancer and Blood Specialty Center - Downtown

🇺🇸

Spokane, Washington, United States

MultiCare Institute for Research & Innovation

🇺🇸

Tacoma, Washington, United States

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