Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

A Phase 2 Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

The purpose of this phase II study is to determine the safety, tolerability, and activity of XL647 in previously untreated subjects with non-small cell lung cancer (NSCLC). XL647 is a small molecule that potently inhibits multiple receptor kinases, including EGFR, VEGFR2 (KDR), ErbB2, and EphB4. Sensitivity to EGFR inhibitors has been linked to specific EGFR mutations and associated with certain clinical characteristics in patients with NSCLC (eg, female, minimal and remote smoking history, and adenocarcinoma histology).

Inclusion Criteria:

• Subject has NSCLC with a histologically confirmed diagnosis of adenocarcinoma with measurable disease (stage IIIB, with malignant pleural effusion, and stage IV) and either has a demonstrated activating mutation of the EGF receptor in tumor tissue or meets one of three criteria: asian, female, and minimal or no smoking history.
• Measurable disease defined according to RECIST
• ECOG performance status of 0 or 1
• Normal organ and marrow function
• No other malignancies within 5 years, except for non-melanoma skin cancer

Exclusion Criteria:

• Radiation to ≥25% of bone marrow within 30 days of XL647 treatment

• Prior systemic anticancer therapy, including cytotoxic chemotherapy, anti-VEGF, anti-VEGFR, or anti-EGFR agents or investigational drug

• Subject has not recovered to ≤ grade 1 or to within 10% of baseline values from adverse events due to other medications administered > 30 days before study enrollment

• Receiving anticoagulation therapy with warfarin (low-dose warfarin < 1 mg/day, heparin and low molecular weight heparins are permitted)

• The subject meets any of the following cardiac criteria:

  • Corrected QT interval (QTc) of > 460 msec
  • Family history of congenital long QT syndrome or unexplained sudden death
  • History of sustained ventricular arrhythmias
  • Has a finding of left bundle branch block
  • Has an obligate pacemaker
  • Has important bradycardia defined as a heart rate of < 50 bpm due to sinus node dysfunction
  • Has uncontrolled hypertension
  • Has symptomatic congestive heart failure, unstable angina, or a myocardial infarction within the past 3 months
  • Has a serum potassium or serum magnesium level that falls outside the normal range

• The subject has progressive symptomatic or hemorrhagic brain or leptomeningeal metastases

• Uncontrolled intercurrent illness

• Subject is pregnant or breastfeeding

• Known HIV