A Phase 2 Study of AZD0530 in Patients With Advanced, Recurrent Non-Small Cell Lung Cancer Who Have Previously Received Platinum-Based Combination Chemotherapy

Inclusion Criteria:

- Histologically or cytologically confirmed non-small cell lung cancer, meeting both of
the following criteria:

- Locally advanced or metastatic (stage IIIB or IV) disease

- Recurrent, unresectable disease

- Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional
techniques or as ≥ 10 mm with spiral CT scan

- Previously treated with first-line platinum-based systemic chemotherapy for advanced
disease AND had at least stabilization of disease as best response to first-line
therapy

- No more than one line of prior therapy

- Previously treated brain metastases allowed provided they are clinically and
radiologically stable and there are no neurological symptoms or requirement for
steroids

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 3 months

- Platelet count ≥ 100,000/mm³

- Leukocytes ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Hemoglobin > 9 g/dL (transfusion allowed)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min

- Urine protein creatinine ratio ≤ 1.0 OR urine protein < 1,000 mg by 24-hour urine
collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to, during, and for 8 weeks
after completion of study treatment

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to AZD0530

- No QTc prolongation (i.e., QTc interval ≥ 460 msec) or other significant ECG
abnormalities

- No cardiac dysfunction including, but not limited to, the following:

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- History of ischemic heart disease, including myocardial infarction

- No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or
diastolic BP ≥ 90 mm Hg)

- No condition that would impair the ability to swallow AZD0530 tablets (e.g.,
gastrointestinal tract disease resulting in an inability to take oral medication,
requirement for IV alimentation, or active peptic ulcer disease)

- No concurrent uncontrolled illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situation that would limit compliance with
study requirements

- No concurrent combination antiretroviral therapy for HIV-positive patients

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C),
radiotherapy, or surgery and recovered

- Prior radiotherapy to target lesions allowed provided there is disease progression

- No prior radiotherapy to > 40% of bone marrow

- No prior EGFR tyrosine kinase inhibitors

- No prior surgical procedures affecting absorption

- No CYP3A4-active agents or substances for 7 days prior to, during, and for 7 days
after completion of study treatment, including any of the following:

- Ketoconazole

- Itraconazole

- Ritonavir

- Mibefradil

- Clarithromycin

- Saquinavir

- Indinavir

- Erythromycin

- Nefazadone

- Fluconazole

- Diltiazem

- Alfentanil

- Carbamazepine

- Cyclosporine

- Tacrolimus

- Lovastatin

- Simvastatin

- No other concurrent investigational agents

- No other concurrent anticancer therapy