Pegylated Irinotecan NKTR 102 in Treating Patients With Relapsed Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To evaluate the 18-week progression free survival (PFS) rate of relapsed small cell lung
cancer (SCLC) patients treated with NKTR-102 (pegylated irinotecan NKTR 102).

SECONDARY OBJECTIVES:

I. To evaluate the objective response rate. II. To evaluate the duration of response. III. To
evaluate the overall survival. IV. To evaluate the toxicity of NKTR-102 in this patient
population.

TERTIARY OBJECTIVES:

I. To explore the correlation between UDP glucuronosyltransferase 1 family, polypeptide A
cluster (UGTIA1) polymorphisms and NKTR-102 toxicities.

OUTLINE:

Patients receive pegylated irinotecan NKTR 102 intravenously (IV) over 90 minutes on day 1.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3
months thereafter.

Inclusion Criteria:

- Written informed consent granted prior to initiation of any study-specific screening
procedures, given with the understanding that the patient has the right to withdraw
from the study at any time, without prejudice

- Histologic or cytologic diagnosis of SCLC (Note: patients with mixed histology are not
eligible)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Presence of measurable disease defined as >= 1 lesion whose longest diameter can be
accurately measured as >= 20 mm with conventional techniques or as >= 10 mm with
spiral computed tomography (CT)

- Previously treated SCLC with only one prior treatment regimen
(cyclophosphamide/doxorubicin/vincristine [CAV] alternating with etoposide/cisplatin
[EP] is acceptable)

- Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, hormonal
therapy, or surgery to National Cancer Institute (NCI)-Common Terminology Criteria for
Adverse Events (CTCAE) version 4.0 grade =< 1, except for diarrhea (which must be
grade 0 without supportive antidiarrheal medications) and alopecia (any grade)

- Platelet count >= 100 x 10^9/L

- Hemoglobin (Hgb) >= 9 gm/dL

- Absolute neutrophil count (ANC) >= 1500/uL

- Serum creatinine =< 1.5 mg/dL or creatinine clearance > 45 mL/min; use either measured
or calculated with Cockcroft-Gault formula

- Serum total bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN or =< 5
x ULN if caused by liver metastasis

- Women of childbearing potential must have a negative pregnancy test performed within
seven days prior to the start of study drug; male and female subjects of child-bearing
potential must agree to use double-barrier contraceptive measures, or avoidance of
intercourse during the study and for 6 months after last investigational drug dose
received

Exclusion Criteria:

- Previous anti-cancer chemotherapy, immunotherapy or investigational agents < 4 weeks
(6 weeks for nitrosoureas or mitomycin C) prior to the first day of study defined
treatment; palliative radiation < 2 weeks, biological therapy within 2 weeks, hormonal
therapy within 1 week prior to day 1 cycle 1

- Prior treatment with a topoisomerase-I inhibitor (e.g., topotecan, irinotecan)

- Prior malignancy except for non-melanoma skin cancer and carcinoma in situ, unless
diagnosed and definitively treated more than 5 years prior to enrollment

- Substance abuse, medical, psychological or social conditions that may, in the opinion
of the Investigator, interfere with the patient's participation in the study or
evaluation of the study results

- Known human immunodeficiency virus (HIV) infection

- Pregnancy or breast-feeding

- Concurrent administration or received cytochrome P450, family 3, subfamily A,
polypeptide 4 (CYP3A4) inducers or inhibitors within 2 weeks prior to the first day of
study drug treatment

- Patients with chronic or acute gastrointestinal (GI) disorders resulting in diarrhea
of any severity grade; patients who are using chronic anti-diarrheal supportive care
(more than 3 days/week) to control diarrhea in the 28 days prior to study entry

- Major surgery < 4 weeks or minor surgery (e.g. talc pleurodesis, excisional biopsy,
etc) < 2 weeks prior to the first day of study defined treatment

- Have central nervous system (CNS) metastases (unless the patient has completed
successful local therapy for CNS metastases and has been off corticosteroids for at
least 4 weeks before starting study therapy); brain imaging is required in symptomatic
patients to rule out brain metastases, but is not required in asymptomatic patients

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Unwilling or unable to follow protocol requirements