Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

This is a multi-arm, multi-cohort, Phase IIa, open-label study of selected small molecules
(gefitinib, AZD9291, or selumetinib + docetaxel) or 1st IMT (hereafter referred to as IMT-A;
tremelimumab) followed by sequential switch to a 2nd IMT (hereafter referred to as IMT-B;
MEDI4736) in locally advanced or metastatic NSCLC (Stage IIIB-IV). Patients will be enrolled
concurrently into multiple cohorts.

Inclusion Criteria:

- Provision of archived tumor tissue sample and mandatory tissue biopsy

- Patients must have either histologically or cytologically documented NSCLC who present
with locally advanced or metastatic stage IIIB-IV disease

- Life expectancy ≥12 weeks

- Patients must have measurable disease and at least 1 lesion not previously irradiated

- World Health Organization (WHO) performance status of 0 or 1

Exclusion Criteria:

- Mixed small cell and NSCLC histology

- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody