ADI-PEG 20 in Combination with Gemcitabine and Docetaxel for the Treatment of Metastatic Non-small Cell and Extensive Stage Small Cell Lung Cancer after Progression on Frontline Therapy

Inclusion Criteria

• Histologically or cytologically confirmed extensive stage small cell or metastatic non-small cell lung cancer that has progressed on frontline therapy who are fit for treatment with gemcitabine and docetaxel in the opinion of the treating physician. Phase II enrollment will occur separately to the small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cohorts, with up to 36 enrolled in each cohort
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Treated with at least one previous line of systemic therapy. The allowable window between treatments is 21 days for chemotherapy or a tyrosine kinase inhibitor (TKI) or 5 half-lives for a TKI (whichever is shorter), 21 days and progression by computerized tomography (CT) for immunotherapy, 21 days for radiation therapy (RT), 21 days for surgery, or 28 days for an investigational agent. * Patients with extensive stage (ES)-SCLC must have been treated with first-line therapy of platinum doublet + anti-PD(L)1 therapy, if eligible. * Patients with NSCLC without a driver mutation must have been treated with first-line therapy of platinum doublet + anti-PD(L)1 therapy, if eligible. * Patients with NSCLC with a driver mutation (EGFR, ALK, ROS1) must have been treated with a Food and Drug Administration (FDA) approved targeted therapy and subsequent platinum doublet therapy, if eligible.
• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Absolute neutrophil count >= 1.5 K/cumm
• Platelets >=100 K/cumm
• Hemoglobin >= 9 g/dL
• Total bilirubin =< 2 x institutional upper limit of normal (IULN), patients with Gilberts must be below 3 x IULN
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SGPT]) <= 3 x IULN (or =< 5 x IULN if liver metastases are present)
• Creatinine clearance > 60 mL/min by Modification of Diet in Renal Disease (MDRD) or by 24 hour urine
• Serum uric acid =< 8 mg/dL (with or without medication control)
• The effects of ADI-PEG 20 on the developing human fetus are unknown. For this reason and because chemotherapeutics are known to be teratogenic, women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for one month after completion of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for one month after completion of study treatment
• Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document

Exclusion Criteria

• A history of other malignancy with the exception of: * Malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease * Basal cell or squamous cell carcinoma of the skin which was treated with local resection only * Carcinoma in situ of the cervix * Other tumors discussed with the study principal investigator (PI)
• Currently receiving any other investigational agents
• Prior treatment with ADI-PEG 20 or gemcitabine (prior docetaxel is allowed)
• Presence of untreated or unstable brain metastases. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose central nervous system (CNS) disease is radiographically stable at study entry, are eligible
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20, gemcitabine, pegylated compounds, or other agents used in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• History of seizure disorder not related to underlying cancer
• Clinically significant grade 2 or higher neuropathy
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry
• Patients with known active Hepatitis B or C or human immunodeficiency virus (HIV)