Pevonedistat and Docetaxel in Treating Patients with Stage IV or Recurrent Non-small Cell Lung Cancer

Inclusion Criteria

• 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 demonstrated progression on or intolerance to platinum-based chemotherapy
• Patients whose tumors harbor an EGFR sensitizing mutation must have demonstrated progression on or intolerance to an Food and Drug Administration (FDA)-approved first-line EGFR tyrosine kinase inhibitor (TKI); patients with the EGFR T790M mutation, must also have demonstrated progression on or intolerance to osimertinib
• Patients whose tumors harbor a ROS1 rearrangement must have demonstrated progression on or intolerance to crizotinib
• Patients whose tumors harbor an ALK rearrangement must have demonstrated progression on or intolerance to an FDA-approved first-line TKI; if the first-line TKI was crizotinib, then they also must have demonstrated progression on or intolerance to an FDA-approved second-line TKI; patients who received alectinib or ceritinib as first-line therapy and have demonstrated progression or intolerance will be eligible for this trial
• Patients whose tumors harbor the BRAF V600E mutation, must have demonstrated progression on or intolerance to the combination of dabrafenib and trametinib
• Patients whose tumors have PD-L1 expression in >= 50% of tumor cells must have demonstrated progression on or intolerance to pembrolizumab; otherwise, patients who are eligible to receive an FDA-approved anti-PD-1/anti-PD-L1 agent as second-line therapy must also have demonstrated progression on or intolerance to the drug
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500/mm^3 (repeat if more than 3 days before the first dose)
• Platelet count >= 100,000/mm^3 (repeat if more than 3 days before the first dose)
• Albumin > 2.7 g/dL (repeat if more than 3 days before the first dose)
• Total bilirubin =< upper limit of normal (ULN) except in patients with Gilbert’s syndrome; patients with Gilbert’s syndrome may enroll if direct bilirubin =< 1.5 x ULN (repeat if more than 3 days before the first dose)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (repeat if more than 3 days before the first dose)
• Creatinine clearance >= 50 mL/min (repeat if more than 3 days before the first dose)
• Hemoglobin >= 8 g/dL; patients may be transfused to achieve this value; elevated indirect bilirubin due to post-transfusion hemolysis is allowed (repeat if more than 3 days before the first dose)
• 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 Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria
• It is preferable that patients have an adequate tissue sample available for correlative studies evaluating SAG expression, cullin neddylation, and KRAS^G12D mutation, but lack of availability of such a tissue sample is not a requirement for trial enrollment

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 * Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load; patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load
• Known hepatic cirrhosis or severe pre-existing hepatic impairment
• Known cardiopulmonary disease defined as: * Unstable angina * Congestive heart failure (New York Heart Association class III or IV) * Myocardial infarction (MI) within 6 months prior to first dose of pevonedistat (patients who had ischemic heart disease resulting in MI and/or revascularization greater than 6 months before treatment and who are without cardiac symptoms may enroll) * Cardiomyopathy * Left ventricular ejection fraction < 50% as assessed by echocardiogram or radionuclide angiography * Clinically significant arrhythmia: ** History of polymorphic ventricular fibrillation or torsade de pointes ** Permanent atrial fibrillation [a fib], defined as continuous a fib for >= 6 months ** Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening ** Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation and ** Patients with paroxysmal a fib or < grade (Gr) 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen * Implantable cardioverter defibrillator * Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing) * Pulmonary hypertension
• 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
• 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 Common Terminology Criteria for Adverse Events (CTCAE) v4.03 grade >= 2