Safety and Efficacy Study of DCVax-Direct in Solid Tumors

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.