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

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
  • 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