Trial of Pevonedistat Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

- Patients 18 years of age or older

- Histologically confirmed stage IV NSCLC (adenocarcinoma, squamous cell carcinoma,
large cell carcinoma, or not otherwise specified) or recurrent NSCLC not amenable to
curative therapy

- Patients must have already received platinum-based chemotherapy; they may have also
received prior immunotherapy or targeted therapy

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (an attempt to
quantify cancer patients' general well-being and activities of daily life. The score
ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)

- Clinical laboratory values within appropriate parameters

- Female patients who are of childbearing potential and all males must agree to practice
true abstinence or use effective methods of contraception

- Patients must be able to understand and sign the informed consent.

- Patients must have measurable disease as defined by RECIST v1.1 criteria

- It is preferable that patients have an adequate tissue sample available

Exclusion Criteria:

- Treatment with any investigational products within 4 weeks before the first dose of
any study drug

- Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of study procedures

- Active uncontrolled infection or severe infectious disease, such as severe pneumonia,
meningitis, or septicemia that require IV antibiotics within 2 weeks of starting study
treatment

- Major surgery within 14 days before the first dose of any study drug or a scheduled
surgery during study period

- Diagnosed or treated for another malignancy within 2 years before randomization or
previously diagnosed with another malignancy and have any evidence of residual
disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
not excluded if they have undergone resection.

- Life-threatening illness unrelated to cancer

- Patients with uncontrolled coagulopathy or bleeding disorder

- Known human immunodeficiency virus (HIV) seropositivity

- Known hepatitis B surface antigen seropositivity or known or suspected active
hepatitis C infection

- Known hepatic cirrhosis or severe pre-existing hepatic impairment

- Known cardiopulmonary disease

- Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mm Hg, diastolic
blood pressure > 95 mm Hg)

- Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to
institutional guidelines

- Interstitial lung disease or pulmonary fibrosis

- Systemic antineoplastic therapy or radiotherapy for other malignant conditions within
14 days before the first dose of any study drug, except for hydroxyurea.

- Symptomatic or history of untreated brain or leptomeningeal metastases. Treated
patients should be neurologically stable for 4 weeks after completion of appropriate
therapy. Patients should be off steroids at least 3 days prior to start of therapy on
clinical trial.

- Treatment with clinically significant metabolic enzyme inducers within 14 days before
the first dose of the study drug. Clinically significant metabolic enzyme inducers are
not permitted during this study (see Appendix III for more details).

- Female patients who are lactating, breastfeeding, or have a positive pregnancy test

- Female patients who intend to donate eggs (ova) during the course of this study or 4
months after receiving their last dose of study drug(s).

- Male patients who intend to donate sperm during the course of this study or 4 months
after receiving their last dose of study drug(s).

- Known hypersensitivity to docetaxel or other drugs formulated with polysorbate 80

- Prior therapy with docetaxel

- Peripheral neuropathy of CTCAE v4.03 grade ≥ 2