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

A Phase IIa, Open-Label, Multi-Center, Multi-Cohort, 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 (Stage IIIB-IV)

Primary objective: To assess the efficacy of various sequences of either a small molecule or an IMT (IMT-A) followed by a IMT-B (MEDI4736) .

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