Stereotactic Body Radiation Therapy (SBRT) Combined With Avelumab (Anti-PD-L1) for Management of Early Stage Non-Small Cell Lung Cancer (NSCLC)

This is a single arm open label Phase I/II study that will consist of two parts. In Phase I,
investigators will assess the safety and tolerability of SBRT combined with Avelumab. In
Phase II, investigators will determine whether SBRT combined with Avelumab improves relapse
free survival. Subjects with Stage I NSCLC who are not undergoing surgical resection will be
candidates for enrollment. Subjects will receive definitive stereotactic body radiation
(SBRT) in 4-5 fractions combined with concurrent and adjuvant Avelumab at 10mg/kg for a total
of 6 cycles. Subjects will be evaluated for safety as measured by the occurrence of adverse
events, serious adverse events, and laboratory abnormalities. Three blood draws will be
obtained to analyze anti-tumor immune responses and immune correlates.

Inclusion Criteria:

- Tumor(s) to be treated is(are) ≤ 5.0 cm or ≤250 cm3

- Stage I NSCLC and is deemed medically inoperable or refuses surgical resection.

- Life expectancy ≥ 9 months.

- Acceptable organ and marrow function

Exclusion Criteria:

- Prior organ transplantation, including allogeneic stem cell transplantation

- Significant acute or chronic infections including:

- Known history of human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS)

- Known history of HBV or HCV

- Active autoimmune disease

- Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease
not requiring immunosuppressive treatment are eligible.

- Subjects requiring hormone replacement with corticosteroids are eligible if the
steroids are administered only for the purpose of hormonal replacement and at
doses ≤ 10 mg or 10 mg equivalent prednisone per day

- Administration of steroids through a route known to result in a minimal systemic
exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable

- Current use of immunosuppressive medication, EXCEPT for the following:

- intranasal, inhaled, topical steroids, or local steroid injection (eg,
intra-articular injection)

- Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or
equivalent

- Steroids as premedication for hypersensitivity reactions (eg, CT scan
premedication).

- Cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to
enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina,
congestive heart failure, or serious cardiac arrhythmia requiring medication.

- Known severe hypersensitivity reactions to monoclonal antibodies any history of
anaphylaxis, or uncontrolled asthma

- Pregnancy or lactation

- Known alcohol or drug abuse

- Prior radiotherapy to the treatment site(s).