Safety and Efficacy Study of DCVax-Direct in Solid Tumors

A PHASE I/II CLINICAL TRIAL EVALUATING DCVax-Direct, AUTOLOGOUS ACTIVATED DENDRITIC CELLS FOR INTRATUMORAL INJECTION, IN PATIENTS WITH SOLID TUMORS

The study comprises a Phase I component during which the optimal dose of DCVax-Direct for the treatment of solid tissue tumors will be identified, followed by a Phase II component to determine if the injection of DCVax-Direct into selected solid tissue tumors has the ability to reduce tumor growth.

Inclusion Criteria (summary):

• Age between 18 and 75 years (inclusive) at screening.
• Karnofsky performance status (KPS) of 70 or higher or Eastern Cooperative Oncology Group (ECOG) 0-1 at screening.
• Subjects with a histological or cytopathological confirmed diagnosis of a locally advanced or metastatic solid tumor malignancy for which primary treatment is no longer effective or does not offer curative or life-prolonging potential per clinician judgment, with the understanding that DCVax-Direct is not intended as a treatment of last resort.
• Not eligible for complete resection due to either tumor location, physician's assessment or subject's choice.
• Must have completed at least one recent treatment regimen in the metastatic or advanced setting in the disease currently under treatment to reduce tumor burden.
• Any steroid therapy >2 mg dexamethasone or equivalent dose should be stopped or have been tapered down 2 weeks prior to the leukapheresis.
• At least one measurable tumor mass, i.e. a lesion that can accurately be measured by CT/MRI in at least one dimension with longest diameter ≥ 1 cm, that is accessible for injection either with or without imaging (CT/ultrasound) guidance.
• Adequate hematological, hepatic, and renal function,
• Adequate blood coagulation parameters
• Life expectation of >3 months.

Exclusion Criteria (Summary):

• Positive HIV-1, HIV-2, or Human T-lymphotropic virus (HTLV-I/II) tests.
• History of current or prior (within the last two years) active clinically significant malignancy other than the tumor type for which DCVax-Direct treatment is considered, and except for primary tumor in the case of metastases and adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Heavily pretreated (HP) subjects are not eligible for this study, unless treatments have occurred more than 1 year in the past.
• Presence of brain metastases, unless treated surgically and/or irradiated and clinically stable off steroids or on low dose (< 2 mg per day) steroids for ≥ 14 days, or presence of leptomeningeal disease.
• History of immunodeficiency or unresolved autoimmune disease.
• Requirement for ongoing immunosuppressants.
• Prior active immunotherapy for cancer within the past 2 years.
• Ongoing medical need for continuous anti-coagulation or anti-platelet medication.
• Known genetic cancer-susceptibility syndromes.
• Acute or active uncontrolled infection
• Ongoing fever ≥ 101.5 degrees F/38.6 degrees C at screening.
• Unstable or severe intercurrent medical conditions such as unstable angina, uncontrolled arrhythmias, Crohn's Disease, ulcerative colitis etc.
• Females of child-bearing potential who are pregnant or lactating or who are not using adequate contraception (surgical, hormonal or double barrier, i.e. condom and diaphragm).
• Allergy or anaphylaxis to any of the reagents used in this study.
• Inability to obtain informed consent because of psychiatric or complicating medical problems.
• Inability or unwillingness to return for required visits and follow-up exams.