Phase II Study of E7389, a Halichondrin B Analog, in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC), Who Progressed During or After Platinum-Based Doublet Chemotherapy Stratified for Prior Taxane Therapy

Inclusion Criteria

INCLUSION CRITERIA:

- Patients must have a histologically or cytologically confirmed diagnosis of non-small
cell lung cancer with at least one site of measurable disease by the RECIST criteria.

- Patients must have failed prior platinum-containing doublet chemotherapy. Patients
who have received single agent chemotherapy with or without a subsequent taxane
containing regimen may be enrolled after discussion with Sponsor.

- Patients must be ≥ 18 years of age.

- Patients must have a performance score of 0 or 1 using the ECOG performance scale.

- Patients must have a life expectancy of ≥ 3 months.

- Patients must have adequate renal function as evidenced by a serum creatinine ≤ 2.0
mg/dL or a calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault
formula.

- Patients must have adequate hepatic function as evidenced by bilirubin ≤1.5 mg/dL and
alkaline phosphatase, AST and ALT ≤ 3 times upper limit of normal, unless there is
evidence of liver metastases, in which case the alkaline phosphatase, AST and ALT
must be ≤ 5 times upper limit of normal.

- Patients must have adequate bone marrow function as evidenced by absolute neutrophil
counts (ANC) ≥ 1.5 X 10^9/L, hemoglobin ≥ 10.0 g/dL (a hemoglobin < 10.0 g/dL would
be acceptable if it can be corrected by growth factor or transfusion), and platelet
count ≥ 100 X 10^9/L.

- Patients must be willing and able to comply with the protocol guidelines for the
duration of the study.

- Patients must be willing and able to complete the Lung Cancer Symptom Scale (LCSS)
instrument.

- The biopsy specimen (paraffin block or at least 10 unstained slides) must be
available from either the initial diagnosis or any subsequent diagnostic or surgical
procedure of patients participating in the pharmacogenomics sub-study only. However,
no additional biopsies are obligatory for participation in this study except those
required for confirmation of the diagnosis.

- Patients must give written informed consent prior to any study-specific screening
procedures with the understanding that the patient may withdraw consent at any time
without prejudice.

EXCLUSION CRITERIA:

- Patients with pre-existing peripheral neuropathy > Grade 2

- Patients who require therapeutic doses of warfarin

- Patients who have not recovered from any chemotherapy, radiation or other therapy
related toxicity deemed to be clinically significant at study entry

- Patients with active symptomatic brain metastases. Patients with central nervous
system (CNS) metastases are considered eligible if they have had adequately treated
brain metastases, i.e. have completed treatment (tapered off steroids) at least four
weeks before starting treatment with E7389. Patients who have no evidence that the
metastases are symptomatic or actively growing (no evidence of midline shift on CT
scan or MRI) may be enrolled without initiation of local therapy for the CNS
metastases. In this case, a repeat scan must be performed within four weeks of the
original scan to ensure that disease progression is not occurring. It is not the
intention of this study to treat patients with active brain metastases.

- Patients who have a positive history for HIV, active hepatitis B or active hepatitis
C.

- Patients with other significant medical, or psychiatric disorders that, in the
opinion of the investigator, will exclude the patient from the study for compliance
or safety reasons

- Patients who have received investigational drugs, including immunotherapy, gene
therapy, hormone therapy (except megestrol acetate for appetite stimulation), or
other biological therapy; conventional chemotherapy or radiation therapy (except for
palliation, defined as less than 10% of the bone marrow reserve and less than 20 Gy),
within three weeks of E7839 enrollment

- Patients who have received non-cytotoxics (eg, gefitinib, erlotinib) within one week
of E7389 enrollment

- Patients who have not recovered from major surgery within three weeks of E7389
enrollment

- Patients with severe/uncontrolled intercurrent illness/infection

- Patients with significant cardiovascular impairment (history of congestive heart
failure>NYHA grade II, unstable angina or myocardial infarction within the past six
months, or serious cardiac arrhythmia)

- Patients with organ allografts

- Patients with hypersensitivity to halichondrin B and/or halichondrin B-related
compounds

- Patients who participated in a prior E7389 clinical trial

- Patients with second malignancy within the past 5 years, except for carcinoma in situ
of the cervix or basal cell carcinoma of the skin

- Women who are pregnant or breast-feeding; woman of childbearing potential with a
positive pregnancy test at screening or no pregnancy test. Women of childbearing
potential unless (1) surgically sterile or (2) using adequate measures of
contraception in the opinion of the Investigator. Perimenopausal women must be
amenorrheic for at least 12 months or using adequate contraception to be considered
of non-childbearing potential.

- Fertile men who are not willing to use contraception or fertile men with a female
partner who is not willing to use contraception