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

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 theAmerican 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 whoreceived adjuvant, neoadjuvant chemotherapy or chemoradiotherapy with curativeintent 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 iswithin therapeutic range of intended use of anticoagulants).

• A female participant is eligible to participate if she is not pregnant, notbreastfeeding

• If male subject with a female partner(s) of child-bearing potential, must agree touse 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 RETtargetable gene rearrangement, and/or METex14 skipping mutation, and/or NTRK1/2 genefusion and/or BRAF V600 mutations directed therapy is indicated or planned for othertargeted 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 ofrandomization.

• Has received prior radiotherapy within 2 weeks of randomization. Subjects must haverecovered from all radiation-related toxicities, not require corticosteroids, andnot have had radiation pneumonitis. A 1-week washout is permitted for palliativeradiation (≤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 activetreatment within the past 3 years.

• Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinomaof the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer insitu) that have undergone potentially curative therapy are not excluded

• Has symptomatic Central Nervous System (CNS) metastases and/or carcinomatousmeningitis. Subjects with asymptomatic CNS metastases or with previously treatedbrain metastases may participate provided they were treated before randomization (ifapplicable) and are neurologically stable and without requirement of steroidtreatment 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 immunosuppressivedrugs).

• 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 ofimmunosuppressive therapy within 7 days prior randomization. Subjects with asthmathat require intermittent use of bronchodilators, inhaled steroids, or local steroidinjections 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 antibodyor 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 deviceduring the 4 weeks prior to randomization.

• Concurrent treatment with other experimental treatments for NSCLC while in thestudy.

• 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.