Clinical trial NCT06216301: LUNAR-2: TTFields With Pembrolizumab + Platinum-based Chemotherapy for Metastatic NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Non-small Cell Lung Cancer
Keywords: NSCLC
Metastatic
Lead sponsor: NovoCure Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-22
Enrollment: 734
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 6 years
measure: Progression Free Survival (PFS)
timeFrame: up to 6 years
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: up to 6 years
measure: Overall Survival (OS)
timeFrame: up to 6 years
measure: Progression Free Survival (PFS)
timeFrame: up to 6 years
measure: Overall Survival (OS)
timeFrame: up to 6 years
measure: Progression Free Survival (PFS)
timeFrame: up to 6 years
measure: 1, 2, and 3-year Survival Rate
timeFrame: up to 6 years
measure: Objective Response Rate (ORR)
timeFrame: up to 6 years
measure: Duration of Response (DoR)
timeFrame: up to 6 years
measure: Disease Control Rate (DCR)
timeFrame: up to 6 years
measure: Progression Free Survival (PFS)
timeFrame: up to 6 years
measure: Objective Response Rate (ORR)
timeFrame: up to 6 years
measure: Duration of Response (DoR)
timeFrame: up to 6 years
measure: Disease Control Rate (DCR)
timeFrame: up to 6 years
measure: Adverse Events
timeFrame: up to 6 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Goodyear
country: United States
facility: Western Regional Medical Center, LLC
state: Arizona
city: Fullerton
country: United States
facility: St. Jude Herritage Medical Group
state: California
city: Newport Beach
country: United States
facility: Hoag Family Cancer Institute - Hoag Memorial Hospital
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: Ocala
country: United States
facility: Florida Cancer Affiliates - Ocala Oncology
state: Florida
city: Plantation
country: United States
facility: BRCR Global
state: Florida
city: Barrington
country: United States
facility: Northwest Oncology & Hematology
state: Illinois
city: Elmhurst
country: United States
facility: Elmhurst Hospital Nancy Knowles Cancer Center
state: Illinois
city: Naperville
country: United States
facility: Edward Cancer Center
state: Illinois
city: Plainfield
country: United States
facility: Edward Cancer Center-Plainfield
state: Illinois
city: Zion
country: United States
facility: Cancer Treatment Centers of America (CTCA)
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Health Indianapolis
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - North
state: Missouri
city: Lee's Summit
country: United States
facility: University of Kansas Cancer Center - Lee's Summit
state: Missouri
city: Overland
country: United States
facility: University of Kansas Cancer Center - Overland Park
state: Missouri
city: Babylon
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: Bronx
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: New Hyde Park
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: New York
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: Patchogue
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: Port Jefferson
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: Riverhead
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: Shirley
country: United States
facility: New York Cancer & Blood Specialists (NYCBS)
state: New York
city: Cary
country: United States
facility: WakeMed Health & Hospitals
state: North Carolina
city: Edinburg
country: United States
facility: DHR Health Oncology Institute
state: Texas
city: Auburn
country: United States
facility: MultiCare Regional Cancer Center
state: Washington
city: Gig Harbor
country: United States
facility: MultiCare Regional Cancer Center
state: Washington
city: Puyallup
country: United States
facility: MultiCare Regional Cancer Center
state: Washington
city: Spokane
country: United States
facility: MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
city: Innsbruck
country: Austria
facility: Universitaetsklinik fuer Innere Medizin V Innsbruck
city: Salzburg
country: Austria
facility: University Hospital Salzburg
city: Vienna
country: Austria
facility: Karl Landsteiner Institut fur Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Gent
country: Belgium
facility: AZ Maria Middelares - Campus Maria Middelares
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc FNOL
city: Ostrava
country: Czechia
facility: Nemocnice Agel Ostrava-Vitkovice / Agel Ostrava-Vitkovice Hospital
city: Farkasgyepu
country: Hungary
facility: Farkasgyepui Tudogyogyintezet
city: Szekszárd
country: Hungary
facility: Tolna Varmegyei Balassa Janos Korhaz
city: Afula
country: Israel
facility: Emek Medical Center
city: Haifa
country: Israel
facility: Bnai zion MC
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Friesland
country: Netherlands
facility: Medisch Centrum Leeuwarden (MCL) - Oncologisch Centrum Leeuwarden (OCL)
city: Harderwijk
country: Netherlands
facility: St. Jansdal ziekenhuis
city: Utrecht
country: Netherlands
facility: St Antonius Ziekenhuis
city: Singapore
country: Singapore
facility: NCCS Singapore
city: Singapore
country: Singapore
facility: Curie Oncology
city: Singapore
country: Singapore
facility: Icon Cancer Centre Singapore (Singapore Oncology Consultants)
city: Elche
country: Spain
facility: Hospital Universitario del Vinalopo
state: Alicante
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucia
city: Barcelona
country: Spain
facility: Clinica Mi Tres Torres Barcelona - Giromed Institute
state: Cataluna
city: Torrejón De Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Baden
country: Switzerland
facility: Kantonsspital Baden
Study officials:
References: