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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.
• Препарат Pembrolizumab
  Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells.
• Препарат Platinum based chemotherapy
  Platinum-based chemotherapy is a standard chemotherapy regimen commonly used in the treatment of non-small cell lung cancer

Первичные конечные точки

• Overall Survival (OS) [Срок оценки: up to 6 years]
• Progression Free Survival (PFS) [Срок оценки: up to 6 years]

Вторичные конечные точки (12)

• Progression Free Survival (PFS) [Срок оценки: up to 6 years]
• Overall Survival (OS) [Срок оценки: up to 6 years]
• Progression Free Survival (PFS) [Срок оценки: up to 6 years]
• Overall Survival (OS) [Срок оценки: up to 6 years]
• Progression Free Survival (PFS) [Срок оценки: up to 6 years]
• 1, 2, and 3-year Survival Rate [Срок оценки: up to 6 years]
• Objective Response Rate (ORR) [Срок оценки: up to 6 years]
• Duration of Response (DoR) [Срок оценки: up to 6 years]
• Disease Control Rate (DCR) [Срок оценки: up to 6 years]
• Progression Free Survival (PFS) [Срок оценки: up to 6 years]
• Objective Response Rate (ORR) [Срок оценки: up to 6 years]
• Duration of Response (DoR) [Срок оценки: up to 6 years]

Критерии участия

Критерии включения

• ≥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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 37 центров

• Central Alabama Research — Birmingham
• Western Regional Medical Center, LLC — Goodyear
• St. Jude Herritage Medical Group — Fullerton
• Hoag Family Cancer Institute - Hoag Memorial Hospital — Newport Beach
• Sutter Institute for Medical Research — Sacramento
• Florida Cancer Affiliates - Ocala Oncology — Ocala
• Moffitt Cancer Center — Tampa
• Northwest Oncology & Hematology — Barrington
• … и ещё 29 центров

Испания · 10 центров

Список центров уточняется — проверьте первичный протокол.

Франция · 8 центров

• Centre Hospitalier Intercommunal de Creteil — Créteil
• CHU Limoges — Limoges
• Hopital Europeen — Marseille
• Hopital Prive du Confluent — Nantes
• Institut Curie — Paris
• CHU de Bordeaux — Pessac
• Centre Hospitalier Lyon Sud — Pierre-Bénite
• Nouvel Hopital Civil (NHC) — Strasbourg

Италия · 8 центров

• A.O. SS. Antonio e Biagio e Cesare Arrigo di Alessandria — Alessandria
• Humanitas Gavazzeni — Bergamo
• Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna — Ferrara
• IRCCS - Istituto Romagnolo per lo Studio Dei Tumori, Dino Amadori — Meldola
• Azienda Sanitaria Territoriale Pesaro Urbino — Pesaro
• Universita Campus Bio-Medico di Roma (UCBM) - Policlinico Universitario — Roma
• Ospedale Isola Tiberina Gemelli — Rome
• Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte — Siena

Германия · 6 центров

• Evangelische Lungenklinik Berlin — Berlin
• University Hospital Giessen, ZIM IV — Giessen
• Krankenhaus Martha-Maria Halle-Dolau — Halle
• Thoraxklinik Heidelberg — Heidelberg
• Klinik Loewenstein gGmbH — Löwenstein
• Pius-Hospital Oldenburg — Oldenburg

Великобритания · 5 центров

Список центров уточняется — проверьте первичный протокол.

Нидерланды · 4 центра

• Rijnstate Ziekenhuis — Arnhem
• Medisch Centrum Leeuwarden (MCL) - Oncologisch Centrum Leeuwarden (OCL) — Friesland
• St. Jansdal ziekenhuis — Harderwijk
• St Antonius Ziekenhuis — Utrecht

Австрия · 3 центра

• Universitaetsklinik fuer Innere Medizin V Innsbruck — Innsbruck
• University Hospital Salzburg — Salzburg
• Karl Landsteiner Institut fur Lungenforschung und pneumologische Onkologie c/o Klinik Flor — Vienna

Чехия · 3 центра

• Fakultni nemocnice Olomouc FNOL — Olomouc
• Nemocnice Agel Ostrava-Vitkovice / Agel Ostrava-Vitkovice Hospital — Ostrava
• General University Hospital in Prague — Prague

Венгрия · 3 центра

• Farkasgyepui Tudogyogyintezet — Farkasgyepű
• Bacs-Kiskun Varmegyei Oktatokorhaz — Kecskemét
• Tolna Varmegyei Balassa Janos Korhaz — Szekszárd

Сингапур · 3 центра

• NCCS Singapore — Singapore
• Curie Oncology — Singapore
• … и ещё 1 центр

Бельгия · 2 центра

• Cliniques universitaires Saint-Luc — Brussels
• AZ Maria Middelares - Campus Maria Middelares — Ghent

Израиль · 2 центра

• Emek Medical Center — Afula
• Bnai zion MC — Haifa

Швейцария · 2 центра

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Япония · 1 центр

• Saitama Medical University International Medical Center — Hidaka

Польша · 1 центр

• Uniwersytecki Szpital Kliniczny — Poznan

Идентификаторы

NCT: NCT06216301 · EF-44

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗