Study of ADI-PEG 20 in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer

Inclusion Criteria:

1. Patients must have histologically documented small cell lung cancer (SCLC)

2. Cohort 1: "Sensitive" disease patients who had one previous line of chemotherapy and maintained an appropriate response for 90 days or more

   Cohort 2:

   • "refractory" disease patients, who had one previous line of chemotherapy and either had no response or progressed in less than 90 days after completing treatment
   • any patient ("sensitive" or "refractory") in need of 3rd line therapy, i.e., who completed or failed two previous lines of chemotherapy
3. Measurable disease using RECIST criteria
4. ASS tumor expression must be either negative or < 5% + tumor cells (by IHC analysis)
5. ECOG performance score of 0 to 2

6. Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted, except for the following laboratory parameters, which must be within the ranges specified:

   • Neutrophil count ≥ 1.5 x 109/L
   • Lymphocyte count ≥ 0.5 x 109/L
   • Platelet count ≥ 50 x 109/L
   • Serum creatinine ≤ 1.5 ULN (or CrCl ≥ 60mL/min)
   • Serum bilirubin ≤ 2mg/dL (or ≤ 34 µmol/L)
   • Serum uric acid ≤ 8mg/dL (or ≤ 0.48 mmol/L)
   • INR ≤ 1.5
   • Partial thromboplastin time ≤ 1.5 x ULN
7. Age ≥ 18 years
8. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Subjects previously treated with ADI-PEG 20
2. Known allergy to pegylated products.
3. History of uncontrolled seizure.
4. Serious illnesses, e.g. serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would interfere with the ability of the patient to fulfill the study requirements.
5. Metastatic disease to the central nervous system, unless treated and stable.
6. Known immunodeficiency or HIV positivity.
7. Participation in any other clinical trial involving another investigational agent within 3 weeks prior to first dosing of study agent.
8. Any other malignancy that requires concomitant therapy restricted according to Section 5.3.
9. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
10. Lack of availability for clinical follow-up assessment.
11. Pregnancy or breast feeding.
12. Refusal or inability to use effective means of contraception for men and women of childbearing potential for the duration of the study.