LUNAR-4: Pilot, Single Arm, Open-Label, Multinational Study of Tumor Treating Fields (TTFields, 150 kHz) Concomitant with Pembrolizumab for the Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC) Previously Treated with a PD-1/PD-L1 Inhibitor and Platinum-Based Chemotherapy

Individuals must meet all of the following inclusion criteria in order to be
eligible to be enrolled and participate in the study:
1. Signed informed consent form.
a. Be >=22 years of age on the day of providing informed consent in the USA.
b. Be >=18 years of age on the day of providing informed consent outside of the
USA.
2. Life expectancy of > 3 months.
3. Histologically or cytologically confirmed diagnosis of NSCLC.
4. Documented positive tumor PD-L1 expression (TPS>=1%).
5. ECOG Score of 0-1.
6. Diagnosis of radiological progression while on or after first platinum-based
systemic therapy administered for advanced or metastatic disease.
Subjects should not receive any systemic therapy after PD-1/PD-L1 Inhibitor +
platinum failure before enrollment into the study. Maintenance therapy after
platinum-based therapy and prior to progression is allowed. Sequence or
combination of PD-1/PD-L1 inhibitor and platinum-based therapy is acceptable.
7. Subjects must have received one line of PD-1/PD-L1 inhibitor therapy for
advanced or metastatic NSCLC. PD-1/PD-L1 inhibitor may have been given alone or
in combination with other therapy.
8. Subjects who received PD-1/PD-L1 inhibitor for advanced disease, must have
had a best response on PD-1/PD-L1 inhibitor of stable disease, partial response
or complete response (in the opinion of the treating physician).
9. Subjects must have experienced disease progression (in the opinion of the
treating physician) more than (>) 84 days following cycle 1 day 1 of their most
recent PD-1/PD-L1 inhibitor therapy. Patients whose most recent line of therapy
was PD-1/PD-L1 inhibitor monotherapy must have also experienced disease
progression during or after prior platinum-based therapy.
10. Subject must have a CT with IV contrast or MRI with IV gadolinium scan of
the brain to evaluate for central nervous system (CNS) disease within 28 days
prior to study enrollment.
11. Adequate hematologic and end-organ function, defined by the following
laboratory test results, obtained within 14 days prior to study enrollment:
I. ANC >= 1.5 x 109/L (1,500/µL) without granulocyte colony-stimulating factor
support
II. Platelet count >= 100 x 109/L (100,000/µL) without transfusion
III. Hemoglobin >= 90 g/L (9 g/dL)
Subjects may be transfused to meet this criterion.
IV. AST, ALT <=2.5 × ULN (<=5 × ULN for subjects with liver metastases)
V. Bilirubin <= 1.5x ULN
VI. Calculated creatinine clearance* (CrCl) >= 15 mL/min
For subjects not receiving therapeutic anticoagulation: INR or aPTT <= 1.5 x ULN
(unless subject is receiving anticoagulant therapy as long as INR or aPTT is
within therapeutic range of intended use of anticoagulants).
12. A female subject 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).
13. 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.
14. Able to operate the NovoTTF-200T device independently or with the help of a
caregiver.
*Creatinine Clearance should be calculated using the Cockcroft-Gault Method

All individuals meeting any of the following exclusion criteria will be
excluded from study enrollment and participation:
1. Mixed small cell and NSCLC histology.
2. Subject must not have leptomeningeal disease or spinal cord compression.
3. Subject must not have brain metastases unless: (1) metastases have been
locally treated and have remained clinically controlled and asymptomatic for at
least 14 days following treatment, and prior to study enrollment, AND (2)
subject has no residual neurological dysfunction and has been off
corticosteroids for at least seven days prior to study enrollment.
4. Contra-indication for PD-1/PD-L1 inhibitor therapy.
5. Subjects must not have received more than one line of PD-1/PD-L1 inhibitor
for advanced disease.
6. Subjects with a known sensitizing mutation for which an Food and Drug
Administration (FDA)-approved targeted therapy for NSCLC exists (e.g., EGFR,
ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2 and MET sensitizing mutations), are
excluded unless previously received at least one of the approved therapy(ies).
Prior targeted therapy for subjects with targetable alterations is allowed if
all other eligibility criteria are also met.
7. Subjects with more than (>) 2 lines of therapy in the advanced setting.
8. Had major surgery <3 weeks prior to Study enrollment.
9. Subject received lung radiation therapy of > 30 Gy within 6 months before
the first dose of study treatment.
10. Has a known additional malignancy that is progressing or has required
active treatment within the past 3 years.
For example: Subjects with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, carcinoma in situ (e.g., breast carcinoma, cervical
cancer in situ), or similar cancers that have undergone potentially curative
therapy are not excluded.
11. 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.
12. 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 study
enrollment. Subjects with asthma that require intermittent use of
bronchodilators, inhaled steroids, or local steroid injections would not be
excluded from the study.
13. 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.
14. Subject must not be receiving or planning to receive another
investigational therapy during study participation.
15. Implantable electronic medical devices (e.g. pacemaker, defibrillator) in
the upper torso.
16. Known allergies to medical adhesives or hydrogel.
17. Admitted to an institution by administrative or court order.