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

December 11, 2025 updated by: NovoCure GmbH

LUNAR-2: Pivotal, Randomized, Open-Label Study of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With Pembrolizumab and Platinum-based Chemotherapy for the Treatment of Metastatic Non-Small Cell Lung Cancer

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

734

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Recruiting
        • Universitaetsklinik fuer Innere Medizin V Innsbruck
        • Contact:
      • Salzburg, Austria, 5020
        • Recruiting
        • University Hospital Salzburg
        • Contact:
      • Vienna, Austria, 1210
        • Recruiting
        • Karl Landsteiner Institut fur Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf
        • Contact:
  • Belgium
      • Brussels, Belgium, 1200
        • Recruiting
        • Cliniques universitaires Saint-Luc
        • Contact:
      • Ghent, Belgium, 9000
  • Czechia
      • Olomouc, Czechia, 779 00
        • Recruiting
        • Fakultni nemocnice Olomouc FNOL
        • Contact:
      • Ostrava, Czechia, 70300
        • Recruiting
        • Nemocnice Agel Ostrava-Vitkovice / Agel Ostrava-Vitkovice Hospital
        • Contact:
      • Prague, Czechia, 12808
        • Recruiting
        • General University Hospital in Prague
        • Contact:
  • France
      • Créteil, France, 94010
        • Recruiting
        • Centre Hospitalier Intercommunal de Créteil
        • Contact:
      • Limoges, France, 87000
        • Recruiting
        • CHU Limoges
        • Principal Investigator:
          • Thomas Egenod
        • Contact:
      • Marseille, France, 13003
      • Nantes, France, 44277
        • Recruiting
        • Hôpital Privé du Confluent
        • Principal Investigator:
          • Cyriac Blonz
        • Contact:
      • Paris, France, 75005
      • Pessac, France, 33604
      • Pierre-Bénite, France, 69495
      • Strasbourg, France, 67091
  • Germany
  • Hungary
      • Farkasgyepű, Hungary, 8582
        • Recruiting
        • Farkasgyepui Tudogyogyintezet
        • Contact:
      • Kecskemét, Hungary, 6000
      • Szekszárd, Hungary, 7100
        • Recruiting
        • Tolna Varmegyei Balassa Janos Korhaz
        • Contact:
  • Israel
      • Afula, Israel, 1834111
        • Recruiting
        • Emek Medical Center
        • Contact:
      • Haifa, Israel, 34561
  • Italy
      • Alessandria, Italy, 15121
      • Bergamo, Italy, 24125
      • Ferrara, Italy, 44124
        • Recruiting
        • Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
        • Contact:
      • Meldola, Italy, 47014
        • Recruiting
        • IRCCS - Istituto Romagnolo per lo Studio Dei Tumori, Dino Amadori
        • Contact:
      • Pesaro, Italy, 61122
        • Recruiting
        • Azienda Sanitaria Territoriale Pesaro Urbino
        • Contact:
      • Roma, Italy, 00128
        • Recruiting
        • Università Campus Bio-Medico di Roma (UCBM) - Policlinico Universitario
        • Contact:
      • Rome, Italy, 00186
      • Siena, Italy, 53100
        • Recruiting
        • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
        • Contact:
  • Netherlands
      • Arnhem, Netherlands, 6815AD
        • Recruiting
        • Rijnstate Ziekenhuis
        • Contact:
      • Friesland, Netherlands, 8934 AD
        • Recruiting
        • Medisch Centrum Leeuwarden (MCL) - Oncologisch Centrum Leeuwarden (OCL)
        • Contact:
      • Harderwijk, Netherlands, 3844 DG
      • Utrecht, Netherlands, 3543 AZ
  • Poland
      • Poznan, Poland, 60-693
        • Recruiting
        • Uniwersytecki Szpital Kliniczny
        • Contact:
  • Singapore
      • Singapore, Singapore, 329563
        • Recruiting
        • Curie Oncology
        • Contact:
      • Singapore, Singapore, 168583
      • Singapore, Singapore, 574623
        • Recruiting
        • Icon Cancer Centre Singapore (Singapore Oncology Consultants)
        • Contact:
  • Spain
      • Barcelona, Spain, 8916
        • Recruiting
        • Institut Catala D'oncologia
        • Contact:
      • Lleida, Spain, 25198
        • Recruiting
        • Hospital Universitario Arnau De Vilanova
        • Contact:
      • Madrid, Spain, 28034
      • Madrid, Spain, 28027
        • Recruiting
        • Clínica Universidad de Navarra (Madrid)
        • Contact:
          • Miguel Fernandez de Sanmamed Gutierrez
          • Phone Number: +34 948255400
          • Email: msanmamed@unav.es
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Regional Universitario de Malaga
        • Contact:
      • Pamplona, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
          • Miguel Fernandez de Sanmamed Gutierrez
          • Phone Number: +34 948255400
          • Email: msanmamed@unav.es
    • Alicante
      • Elche, Alicante, Spain, 3293
        • Recruiting
        • Hospital Universitario del Vinalopó
        • Contact:
    • Andalusia
      • Seville, Andalusia, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio
        • Contact:
    • Catalonia
      • Barcelona, Catalonia, Spain, 8017
        • Recruiting
        • Clinica Mi Tres Torres Barcelona - Giromed Institute
        • Contact:
    • Madrid
      • Torrejón de Ardoz, Madrid, Spain, 28850
        • Recruiting
        • Hospital Universitario de Torrejon
        • Contact:
  • Switzerland
      • Baden, Switzerland, 5404
      • Fribourg, Switzerland, 1752
        • Recruiting
        • HFR Freiburg-Kantonsspital
        • Principal Investigator:
          • Alessandra Curioni-Fontecedro
        • Contact:
  • United States
    • Alabama
    • Arizona
      • Goodyear, Arizona, United States, 85338
    • California
      • Fullerton, California, United States, 92835
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Hoag Family Cancer Institute - Hoag Memorial Hospital
        • Contact:
      • Sacramento, California, United States, 95816
    • Florida
      • Ocala, Florida, United States, 34474
        • Recruiting
        • Florida Cancer Affiliates - Ocala Oncology
        • Contact:
      • Tampa, Florida, United States, 33612
    • Illinois
      • Barrington, Illinois, United States, 60010
      • Elmhurst, Illinois, United States, 60126
        • Recruiting
        • Elmhurst Hospital Nancy Knowles Cancer Center
        • Contact:
      • Naperville, Illinois, United States, 60540-6766
      • Zion, Illinois, United States, 60099
        • Recruiting
        • Cancer Treatment Centers of America (CTCA)
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46237
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Cancer Center
        • Contact:
    • Missouri
      • Annapolis, Missouri, United States, 21401
        • Recruiting
        • Luminis Health Radiation Oncology - Anne Arundel Health System
        • Contact:
      • Kansas City, Missouri, United States, 64154
        • Recruiting
        • University of Kansas Cancer Center - North
        • Contact:
      • Lee's Summit, Missouri, United States, 64064
        • Recruiting
        • University of Kansas Cancer Center - Lee's Summit
        • Contact:
      • Overland, Missouri, United States, 66210
        • Recruiting
        • University of Kansas Cancer Center - Overland Park
        • Contact:
    • New York
      • New Hyde Park, New York, United States, 11042
        • Recruiting
        • New York Cancer & Blood Specialists (NYCBS)
        • Contact:
      • New York, New York, United States, 10028
        • Recruiting
        • New York Cancer & Blood Specialists (NYCBS)
        • Contact:
      • Rochester, New York, United States, 14642
      • Shirley, New York, United States, 19967
        • Recruiting
        • New York Cancer & Blood Specialists (NYCBS)
        • Contact:
      • The Bronx, New York, United States, 10469
        • Recruiting
        • New York Cancer & Blood Specialists (NYCBS)
        • Contact:
    • North Carolina
      • Cary, North Carolina, United States, 27518
        • Recruiting
        • WakeMed Health & Hospitals
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • AHN Cancer Center
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75235
      • Dallas, Texas, United States, 75235
      • Edinburg, Texas, United States, 78539
        • Recruiting
        • DHR Health Oncology Institute
        • Contact:
      • Richardson, Texas, United States, 75082
        • Recruiting
        • Methodist Richardson Cancer Center
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Jason Bates at University of Texas Health Science Center
        • Contact:
    • Washington
      • Auburn, Washington, United States, 98001
      • Gig Harbor, Washington, United States, 98335
      • Puyallup, Washington, United States, 98372
      • Spokane, Washington, United States, 99218
        • Recruiting
        • MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
        • Contact:
      • Tacoma, Washington, United States, 98405
        • Recruiting
        • MultiCare Institute for Research & Innovation
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: NovoTTF-200T, Pembrolizumab, and Platinum-based Chemotherapy
Subjects in this arm receive three treatments - TTFields using the NovoTTF-200T device, pembrolizumab, and platinum-based chemotherapy.
Drug: Pembrolizumab
Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells.
Drug: Platinum based chemotherapy
Platinum-based chemotherapy is a standard chemotherapy regimen commonly used in the treatment of non-small cell lung cancer
Device: NovoTTF-200T
The NovoTTF-200T is a portable, battery operated system intended for continuous home use, which delivers TTFields at a frequency of 150kHz to the subject by means of insulated transducer arrays. TTFields physically disrupt the rapid cell division exhibited by cancer cells. The physical disruption induced by TTFields can lead to to downstream immunogenic cell death.
Active Comparator: Arm 2: Pembrolizumab and Platinum-based Chemotherapy
Subjects in this arm receive two treatments - pembrolizumab and platinum-based chemotherapy.
Drug: Pembrolizumab
Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells.
Drug: Platinum based chemotherapy
Platinum-based chemotherapy is a standard chemotherapy regimen commonly used in the treatment of non-small cell lung cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 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).
up to 6 years
Progression Free Survival (PFS)
Time Frame: 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)
up to 6 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: up to 6 years
Progression Free Survival (PFS) per RECIST v1.1 as assessed by BICR, 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 histology.
up to 6 years
Overall Survival (OS)
Time Frame: up to 6 years
Overall Survival (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 histology.
up to 6 years
Progression Free Survival (PFS)
Time Frame: up to 6 years
PFS per RECIST v1.1 as assessed by BICR, 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 Tumor Proportion Score (TPS).
up to 6 years
Overall Survival (OS)
Time Frame: 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.
up to 6 years
Progression Free Survival (PFS)
Time Frame: up to 6 years
PFS per RECIST v1.1 as assessed by BICR at 6 (PFS6), 12 (PFS12), 24 (PFS24), and 36 (PFS36) months in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.
up to 6 years
1, 2, and 3-year Survival Rate
Time Frame: up 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.
up to 6 years
Objective Response Rate (ORR)
Time Frame: up to 6 years
Objective Response Rate (ORR) per RECIST v1.1 as assessed by BICR, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.
up to 6 years
Duration of Response (DoR)
Time Frame: up to 6 years
Duration of Response (DoR) per RECIST v1.1 as assessed by BICR, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.
up to 6 years
Disease Control Rate (DCR)
Time Frame: up to 6 years
Disease Control Rate (DCR) per RECIST v1.1 as assessed by BICR, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy and of those treated with pembrolizumab and platinum-based chemotherapy alone.
up to 6 years
Progression Free Survival (PFS)
Time Frame: 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.
up to 6 years
Objective Response Rate (ORR)
Time Frame: 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.
up to 6 years
Duration of Response (DoR)
Time Frame: 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.
up to 6 years
Disease Control Rate (DCR)
Time Frame: 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.
up to 6 years
Adverse Events
Time Frame: up 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.
up to 6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NovoCure GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 31, 2024

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

December 29, 2023

First Submitted That Met QC Criteria

January 10, 2024

First Posted (Actual)

January 22, 2024

Study Record Updates

Last Update Posted (Actual)

December 17, 2025

Last Update Submitted That Met QC Criteria

December 11, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EF-44

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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