A Study of CAN008 for Newly Diagnosed Glioblastoma Multiforme

A Phase I Study of CAN008 Plus Concomitant Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme

To evaluate CAN008 safety, tolerability, and pharmacokinetics (PK) of CAN008 when administered concurrent Plus Concomitant Temozolomide During and After Radiation Therapy in Patients with Newly Diagnosed Glioblastoma Multiforme.

CAN008 is a glycosylated fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of human IgG1. CAN008 blocks the interaction between CD95 and its cognate ligand CD95L. The target of CAN008 is the inhibition of CD95L. CD95L is expressed in glioblastoma whose cells are resistant to CD95-mediated apoptosis. CD95L was shown to be a crucial trigger in invasion and migration of tumor cells and neutralizing CD95L abolishes the invasive capacity of glioblastoma cells.

The purpose of the study is:

1. To describe the toxicity associated with this regimen in adult patients with newly diagnosed glioblastoma multiforme.
2. To determine the duration of disease free survival and overall survival associated with this therapy.

Inclusion Criteria:

• Newly diagnosed and histologically confirmed glioblastoma multiforme
• Tumor must be surgically accessible and tissue must be available
• Age ≥ 20 years and < 75 years
• Life expectancy ≥ 6 months
• Baseline MRI images must be done within 2 days after surgery
• Patients must have a Karnofsky performances score ≥ 60 prior to treatment.
• Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
• Adequate hematologic (absolute neutrophil count (ANC) ≥ 1.5x109/L, platelet count ≥ 100x109/L, hemoglobin ≥ 10 g/dL ), renal (creatinine ≤ 1.25xULN ), and hepatic function (total bilirubin ≤ 1.5xULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN)
• Women with childbearing potential must have a negative serum pregnancy test less than 7 days prior to the first dose of study drug.
• Both men and women of reproductive potential agree to use approved contraception, such as condom and placement of an intrauterine device (IUD), during the study and until 3 months after the discontinuation of study treatment.
• Willing and able to comply with the protocol as judged by the investigator
• Patients must provide written consent

Exclusion Criteria:

• Any prior chemotherapy (including carmustine-containing wafers) or immunotherapy (including vaccine therapy )
• Any prior radiotherapy to the brain
• Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial
• Any contraindication to TMZ listed in the local label
• Low-grade astrocytoma
• Unable to undergo MRI
• Past medical history of disease with poor prognosis according to the judgment of the Investigator
• HIV infection
• Patients with positive anti-HCV
• Patients with positive HbsAG who received any related treatment within the past 6 months
• Patients suffering from hereditary fructose intolerance (HFI).
• Patients receive any investigational agent(s) or device(s) within 30 days prior to entering the study
• Known coronary artery disease, significant arrhythmias or severe congestive heart failure