Phase 1 Trial of PAN-301-1 (SNS-301) in Cancer Patients

This is a Phase I, open-label, parallel design study of PAN-301-1 (SNS-301), a HAAH directed nanoparticle vaccine, given intradermally in cohorts of patients with biochemically relapsed prostate cancer, using a fixed dose escalation schema every 21 days.

Human aspartyl-asparaginyl-β-hydroxylase (HAAH), also known as aspartate-β-hydroxylase, is an \~86 kDa type 2 transmembrane protein that belongs to the α-ketoglutarate-dependent dioxygenase family. It is a highly conserved enzyme, which catalyzes the hydroxylation of aspartyl and asparaginyl residues in epidermal growth factor-like domains of proteins including Notch and homologs. HAAH was initially identified in a novel screen to identify cell surface proteins up-regulated in liver cancer. It has subsequently been detected in a diverse array of solid and blood cancers, including: liver, bile duct, brain, breast, colon, prostate, ovary, pancreas, and lung cancers as well as leukemia. HAAH is not found in significant quantities in normal tissue or in proliferative disorders.

The investigators have designed a bacteriophage lambda system to display HAAH peptides fused at the C terminus of the head protein gpD of phage lambda. The phage carry 200-300 copies of the gpD protein on their head and thus display many copies of an approximately 25 kDa molecular weight fragment of HAAH on their surface. The drug substance is one of these HAAH bacteriophage lambda constructs: HAAH-1λ (PAN-301-1).

This study evaluates the safety and immunogenicity of the PAN-301-1 vaccine in patients with biochemically-relapsed prostate cancer.

Eligibility Criteria:
Inclusion Criteria:

1. Signed and dated written Ethics Committee approved informed consent
2. Men aged 21 to 85 years with a histologic diagnosis of prostate cancer with a biochemical relapse following definitive local therapy (RP or radiation therapy)
3. Patients are not eligible or are unwilling to receive additional definitive therapy following relapse (either RP or radiation therapy)
4. No prior cytotoxic chemotherapy for the current cancer
5. Normal electrocardiogram (ECG) or ECG with no clinically significant findings as determined by the Principal Investigator
6. Presence of biochemically relapsed prostate cancer defined as either: 1) PSA \> 2 ng/mL 1 year following initial definitive treatment for prostate cancer: or, 2) PSA doubling time (greater than 0.2 ng/mL) \< 12 months; or, 3) PSA velocity \> 2 ng/mL/year at any time following radical prostatectomy or radiation therapy.
7. Positive expression of HAAH in either archived tumor tissue (if available) or fresh serum
8. No clinical or radiologic evidence of distant metastatic disease as measured by pelvic MRI or CT scan in addition to bone scan. These studies will need to be performed within 56 (+ 7 days) days prior to the start of the study.
9. No history of immunosuppressive disease
10. No evidence of active autoimmune disease. Active autoimmune disease is defined as any disease process that has specifically needed administration of immune suppressive and or cytoreductive therapy currently or within the last 1 year.
11. Able and willing to comply with all study procedures

Exclusion criteria:

1. PSA doubling time of \< 3 months
2. Participation in a clinical trial within 30 days prior to enrollment
3. Prior major surgery or radiation therapy within 4 weeks of enrollment
4. Any illness or condition that in the opinion of the Investigator may affect the safety of the patient or the evaluation of any study endpoint
5. Screening blood counts of the following:

   Hematopoietic:

   Absolute neutrophil count \< 1500/μL, Platelets \< 100,000/μL, Hemoglobin \< 9 g/dL;

   Liver/Metabolic:

   Alanine aminotransferase (ALT) and aspartate transaminase (AST) \> 2.5 × ULN range, Total bilirubin \> 2 × ULN, Albumin \< 2.8 g/dL;

   Renal:

   Creatinine clearance \< 50 mL/min as predicted by the Cockcroft-Gault formula
6. Subjects whose partners are WOCBP must use an adequate method of birth control while on study drug and at least for 3 weeks after discontinuation of study drug
7. Current or anticipated concomitant immunosuppressive therapy (excluding nonsystemic inhaled, topical skin and/or eye drop-containing corticosteroids)
8. Any concurrent condition requiring the continued use of systemic steroids (see above) or the use of immunosuppressive agents including methotrexate. All other systemic corticosteroids must be discontinued at least 4 weeks prior to first study treatment
9. Receipt of any blood product within 1 month of enrollment
10. Receipt of any vaccine within 4 weeks of enrollment
11. Active drug or alcohol use or dependence that, in the opinion of the Investigator, would interfere with adherence to study requirements
12. Been imprisoned or compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e. infectious disease) illness
13. Patients who have a history of coagulopathies, thrombosis or who are receiving active anticoagulation for any condition, such as but not limited to, artificial heart valves, atrial fibrillation, etc.
14. Any other conditions judged by the Investigator that would limit the evaluation of a subject