A clinical trial to evaluate if CC-486 plus pembrolizumab works and is safe in patients with advanced or metastatic non-small cell lung cancer who have previously received platinum containing treatment.

Prior treatment

• Subject has received more than one line of therapy for stage IIIB or IV disease.
• Subject has received prior therapy with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanism
• Subject has had radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting IP, and/or from whom ≥ 30% of the bone marrow was irradiated.
• Subject has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
• Subject with uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. *Subjects with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases (must include radiotherapy and/or surgery) >= 28 days (>= 14 days for stereotactic radiosurgery). Patients must not be receiving corticosteroids for brain metastases.

Other illness

• Subject has active autoimmune disease that has required systemic treatment within the past 2 years

Lab values

• Subject with non-squamous histology has known or unknown sensitizing EGFR and/or positive ALK mutation Note: Subjects with squamous histology and unknown EGFR and ALK mutational status are eligible.

• Subject is ≥ 18 years of age at the time of signing the informed consent form.
• Subject has histologically or cytologically confirmed squamous or nonsquamous NSCLC.
• Subject has stage IIIB or IV NSCLC and was pretreated with only 1 prior systemic platinum based chemotherapy.
• Subject has provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated to assess for PD-L1 status.
• Subject has radiographically-documented measurable disease, as per RECIST 1.1.
• Subject has an ECOG performance status of 0 to 1.
• Subject has adequate organ and bone marrow functions