Neoadjuvant Immunoradiation for Resectable Non-Small Cell Lung Cancer

Inclusion Criteria:

- Written informed consent and any locally-required authorization obtained.

- Histologically-confirmed diagnosis of stage IIIA non-small cell lung cancer (NSCLC)

- Age≥18 years

- Life expectancy >6 months

- Body weight >30kg

- Subjects with non-small cell lung cancer deemed surgically resectable by an attending
thoracic surgeon with lobectomy

- ECOG Performance Status 0-1

- Normal bone marrow and organ function on routine laboratory tests, as defined in
section 4.1

- Evidence of post-menopausal status or negative urinary/serum pregnancy test for female
pre-menopausal subjects. Women will be considered post-menopausal if they have been
amenorrheic for 12 months without an alternative medical cause.

- Ability to understand and willingness of sign consent form

- Willingness to comply with the protocol for the duration of the study

Exclusion Criteria:

- Involvement in the planning and/or conduct of the study (includes AstraZeneca staff
and staff at the study site)

- Prior investigational therapy within 28 days/at least 5 half-lives before study drug
administration

- Prior chest radiation

- Prior history of interstitial lung disease or pneumonitis requiring corticosteroids,
or active non-infectious pneumonitis

- Patients only suitable for surgical management with pneumonectomy, deemed by an
attending thoracic surgeon

- Prior therapy with PD-1, PD-L1, CTLA-4 or anti-cancer vaccines, including durvalumab
and tremelimumab

- Participation in another clinical study with an investigational product in the last 4
weeks or equivalent of 5 half-lives of the first dose of study treatment, whichever is
shorter

- History of another primary malignancy except for: malignancy treated with curative
intent and with no known active disease for the last 5 years, adequately treated
non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately
treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ

- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab or tremelimumab. The following are exceptions to this criterion:

- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)

- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent

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

- Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy

- Subjects with irreversible toxicity that is not reasonably expected to be exacerbated
by the investigational product may be included (e.g., hearing loss, peripherally
neuropathy)

- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable

- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of the first dose of study drug.

- Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
acceptable

- History of allogenic organ transplantation.

- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion (vitiligo or alopecia; hypothyroidism (eg, following Hashimoto syndrome)
stable on hormone replacement; any chronic skin condition that does not require
systemic therapy; active disease in the last 5 years may be included but only after
consultation with the study physician; celiac disease controlled by diet alone.)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent

- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA.

- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab or tremelimumab

- Female subjects who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control.

- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study result.

- Known allergy or hypersensitivity to IP or any excipient

- Uncontrolled psychiatric illness/social situations that would limit compliance with
study requirements or compromise the ability of the subject to give written consent

- Any condition that, in the opinion of the investigator would interfere with evaluation
of study treatment or interpretation of patient safety or study results.