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

1. a. >=22 years of age in the USA b. >=18 years of age outside of the USA.
2. 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.
3. Evaluable (measurable or non-measurable) disease in the thorax per RECIST
v1.1.
4. 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.
5. Have provided tumor tissue from locations not radiated prior to biopsy;
formalin - fixed specimens after the subject has been diagnosed with metastatic
disease will be preferred for determination of PD-L1 status assessed locally
prior to randomization.
6. ECOG Performance Status (PS) of 0-1.
7. Adequate hematologic and end-organ function, defined by the following
laboratory test results, obtained within 14 days prior to randomization:
o ANC >= 1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor
support
o Platelet count >= 100 x 109/L (75,000/µL) without transfusion
o Hemoglobin >= 90 g/L (9 g/dL)
Subjects may be transfused to meet this criterion.
o AST, ALT <=2.5 × ULN (<=5 × ULN for participants with liver metastases)
o Serum bilirubin <= 1.5x ULN
o Serum creatinine <= 1.5 x ULN
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).
8. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP)
b. A WOCBP who agrees to use two adequate barrier methods or a barrier method
plus a hormonal method during the treatment period and for at least 120 days
after the last dose of study therapy. Such methods of contraception, or true
abstinence from heterosexual activity, when this is in line with the preferred
and usual lifestyle of the subject, are required (periodic abstinence, e.g.,
calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are
not acceptable methods of contraception).
9. If male subject with a female partner(s) of child-bearing potential, must
agree to use an effective contraception method based on the recommendation of
the investigator or a gynecologist, starting with the first dose of study
therapy through 120 days after the last dose of study therapy. Males with
pregnant partners must agree to use a condom; no additional method of
contraception is required for the pregnant partner.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. All subjects must sign written informed consent.
11. Able to operate the NovoTTF-200T system independently or with the help of a
caregiver.

1. Mixed small cell and NSCLC histology.
2. 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.
Source documentation of the applicable driver mutations should be available at
the site. Note: For subjects enrolled who are known to have a tumor of
predominantly squamous histology, molecular testing for EGFR mutation, ALK
translocation and ROS1 and/or RET gene rearrangements, and/or METex14 skipping
mutation, and/or NTRK1/2 gene fusion will not be required as this is not
standard of care and is not part of current diagnostic guidelines.
3. Has received systemic therapy for metastatic disease.
4. Had major surgery <3 weeks prior to randomization
5. Received radiation therapy to the lung that is > 30 Gy within 6 months of
randomization.
6. 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.
7. Is expected to require any other form of antineoplastic therapy while on
study.
8. 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.
9. 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.
10. 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). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
11. 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.
12. 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. Examples of such antibodies
include (but are not limited to) antibodies against IDO, PD-L1, IL-2R, GITR.
13. Participation in another clinical study with an investigational agent or
device during the 4 weeks prior to randomization.
Note: Participants who have entered the follow-up phase of an investigational
study may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
14. Concurrent treatment with other experimental treatments for NSCLC while in
the study.
15. Significant comorbidity which is expected to affect the subject*s prognosis
or ability to receive the study therapy:
a) History of significant cardiovascular disease unless the disease is well
controlled.
Significant cardiac disease includes second/third-degree heart block;
significant ischemic heart disease; poorly controlled hypertension; congestive
heart failure of the New York Heart Association (NYHA) Class II or worse
(slight limitation of physical activity; comfortable at rest, but ordinary
activity results in fatigue, palpitation or dyspnea).
b) History of arrhythmia that is symptomatic or requires treatment. Subjects
with atrial fibrillation or flutter controlled by medication are not excluded
from participation in the study.
c) Any serious underlying medical condition (including active infection) that
would impair the ability of the subject to receive protocol therapy.
d) History of any psychiatric condition that might impair the subject*s ability
to understand or comply with the requirements of the study or to provide
consent.
e) Known medical condition that, in the investigator*s opinion, would increase
the risk associated with study participation or study drug administration or
interfere with the interpretation of safety results.
16. Implanted pacemaker, defibrillator, or other electrical medical devices in
the torso.
17. Known allergies or hypersensitivity to medical adhesives, hydrogel.
18. Has a known sensitivity to any component of the planned systemic therapies
(pembrolizumab, cisplatin/carboplatin, pemetrexed/paclitaxel/nab-paclitaxel) .
19. Pregnant or breastfeeding (all subjects of childbearing potential must use
effective contraception method based on the recommendation of the investigator
or a gynecologist for up to 120 days after the last dose of pembrolizumab and
through 180 days after last dose of chemotherapy).
20. Admitted to an institution by administrative or court order.
21. Any medical contraindication to treatment with platinum-based doublet
chemotherapy or pembrolizumab as listed in the local labelling.