STUDY SUMMARY

An open-label, multi-center, 2-arm Phase I/II trial of LBY135 alone and in combination with capecitabine in advanced solid tumors.

TREATMENT OVERVIEW

• Each treatment cycle is 21 days.
• Patients may continue study treatment as long as they experience benefit and do not present unacceptable toxicity or disease progression.
• Patient should be seen by the physician at least every 1-2 weeks.

PRE-TREATMENT ASSESSMENTS

• PET
• Cardiac Imaging
• WHO Performance Status
• Chest X-Ray
• Urinalysis
• Serum Pregnancy
• ECG
• Biomarker
• Tumor Biopsy (if available)

ENTRANCE CRITERIA FOR PARTICIPATION IN TRIAL

INCLUSION CRITERIA

• Patients with histologically confirmed diagnosis of an advanced solid tumor who are presenting with disease which has progressed despite standard therapy of for which standard treatment options do not exist
• In arm 2: Patients with histologically confirmed diagnosis of an advanced solid tumor who are presenting with disease which has progressed despite standard therapy or for which standard treatment options do not exist, and who are considered appropriate for capecitabine treatment
• Measurable or non-measurable disease are determined by the Modified RECIST criteria
• WHO performance status =2
• Patients must have the following laboratory values:
  • Absolute Neutrophil Count (ANC) =1.5 x 109/L
  • Hemoglobin (Hgb) =9 g/dL
  • Platelets =100 x 109/L
  • Serum total bilirubin =1.5 x ULN (upper limit of normal)
  • ALT or AST =2.5 x ULN in the absences of liver metastases; =5.0 x ULN if liver metastases are present
  • Serum creatinine =1.5 x ULN or 24-hour creatinine clearance =50 mL/min

• Additional inclusion criteria for CRC dose expansion cohorts (Arm 1B/2A):
• Measurable disease as determined by the Modified RECIST criteria
• Arm 1 (single agent LBY135): Patients with histologically-confirmed diagnosis of CRC who are presenting with advanced unresectable or metastatic disease (stages IV and IIIb according to AJCC criteria) and for whom standard treatment options do not exist
• Arm 2 (LBY135 plus capecitabine): Patients with histologically-confirmed diagnosis of CRC who are presenting with advanced unresectable or metastatic disease (stages IV and IIIb according to AJCC criteria) who are relapsed after or refractory to at least one but not more than two prior systemic therapies (i.e. chemotherapies, targeted therapies or immunotherapies) for unresectable or metastatic disease

EXCLUSION CRITERIA

• Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
• Acute or chronic liver disease or renal disease
• Patients with any peripheral neuropathy = CTCAE grade 2
• Patients with unresolved diarrhea = CTCAE grade 2
• Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
  • Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
    • Angina pectoris =3 months prior to starting study drug
    • Acute myocardial infarction =3 months prior to starting study drug
    • Other clinically significant heart disease (e.g. symptomatic congestive heart failure, uncontrolled arrhythmia, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)

o Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. uncontrolled diabetes, active or uncontrolled
infection) that could cause unacceptable safety risks or compromise compliance with the protocol

• Patients with known autoimmune disease
• Patients with known anti-murine antibody responses
• Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, erythropoietin) =2 weeks prior to starting study drug
• Patients who are currently receiving corticosteroids or any other immunosuppressive treatment and the treatment cannot be discontinued prior to starting study drug
• Patients who have received chemotherapy, targeted therapy or immunotherapy= 4 weeks ( 6 weeks for nitrosourea, mitomycin-C, or monoclonal antibodies) prior to starting study drug or who have not recovered from side effects of such therapy
• Patients who have received any continuous-dosing therapeutic modalities or investigational drug =5 half lives prior to starting study drug or who have recovered from side effects of such therapy
• Patients who have received wide field radiotherapy =4 weeks or limited field radiation for palliation =2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. For the expansion stages in CRC of Arm 1 and Arm 2, the site of radiotherapy should not be the only site of measurable disease unless there is evidence of disease progression at this site prior to entry on this study
• Patients who have undergone major surgery =2 week prior to starting study drug or who have not recovered from side effects or such therapy
• Patients with history of another primary malignancy that is currently clinically significant, has potential for metastases or currently requires active intervention.
• Patients with contraindications to capecitabine treatment
• Patients who are taking therapeutic doses or warfarin sodium (Coumadin®), or any other coumarin-derivative anticoagulants. The administration of low-molecular weight heparin is allowed

*** POSTED OCTOBER 3, 2006 ***