Pembrolizumab + Idelalisib for Lung Cancer Study

This is a phase 1b/2 study to determine the safety and effectiveness of the combination of
pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune
therapy. Pembrolizumab is an anti-PD-1 immunotherapy that is given intravenously and is
approved for treatment of malignant NSCLC. Idelalisib is the first-in-class oral PI3K-δ
inhibitor that is approved for treatment of certain forms of leukemia and lymphoma.

Immune checkpoint inhibitors (such as anti-PD-1) are effective in treating NSCLC as a single
agent, but overall response isn't optimal; overall response rates (ORR) are only ~20% on
average. The goal of this study is to see whether combining standard therapy with additional
immune modulators will increase response rates, compared to the response seen with
pembrolizumab monotherapy.

All subjects must have documented metastatic or recurrent NSCLC from biopsy. They must have
failed or progressed on platinum-based chemotherapy (e.g. cisplatin, carboplatin) as well
as immune checkpoint inhibitor therapy (e.g nivolumab or pembrolizumab). Patients with
EGFR/ALK mutations/translocations must have failed or progressed on small molecule
inhibitor therapies (e.g. erlotinib, afatinib, etc.).

Inclusion Criteria:

- Have at least one measurable lesion

- Have an ECOG Performance Status of 1 or less

- Demonstrate adequate organ function as defined in the protocol.

- Female subjects of childbearing potential must have a negative pregnancy test before
starting treatment; they must also be willing to use two methods of birth control or
abstain from heterosexual activity for the duration of the study.

- Male subjects must agree to use an adequate method of contraception starting with the
first dose of study therapy through the duration of the study.

Exclusion Criteria:

- Is currently receiving study drug in another trial; or has participated in an
investigational drug study within 3 weeks of the first dose of treatment.

- Is within 3 weeks of most recent chemotherapy.

- Has a history of hypersensitivity to pembrolizumab or idelalisib, or any of their
excipients.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated, stable, brain metastases may
participate; carcinomatous meningitis is excluded regardless of clinical stability.

- Has known history of non-infectious pneumonitis that required steroid use or has
current pneumonitis.

- Has a known history of active TB (Bacillus Tuberculosis)

- Has active autoimmune disease that has required treatment; known history of Human
Immunodeficiency Virus (HIV); known active Hepatitis B or Hepatitis C.

- Has an active infection requiring systemic therapy.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial