Prostate Cancer
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALPAN-301-1
Sponsors
Accelovance
Sensei Biotherapeutics, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
21 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | Through the 21 day interval after the first dose of vaccine |
Secondary
| Measure | Time frame |
|---|---|
| Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events | Through study completion, an average of 3 months. Patients were able to continue on treatment with one patient receiving approximately 15 months of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 PAN-301-1 vaccine is administered intradermally in 3 cohorts of patients in a dose escalation schema every 21 days In this cohort it is administered as SNS-301 2.0 x 10\^10 particles/administration intradermally once every 21 days. Then from 6th treatment visit escalated within same patient to dose 10\^11 particles/administration intradermally once every 21 days. Then from 11th treatment visit escalated within same patient to dose 3 X 10\^11 particles/administration intradermally once every 21 days. | 3 |
| Cohort 2 PAN-301-1 vaccine is administered intradermally in 3 cohorts of patients in a dose escalation schema every 21 days In this cohort it is administered as SNS-301 1.0 x 10\^11 particles/administration intradermally once every 21 days. Then from 6th treatment visit escalated within same patient to dose 3 X 10\^11 particles/administration intradermally once every 21 days. | 3 |
| Cohort 3 PAN-301-1 vaccine is administered intradermally in 3 cohorts of patients in a dose escalation schema every 21 days In this cohort it is administered as SNS-301 3.0 x 10\^11 particles/administration intradermally once every 21 days. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 5 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 67 years STANDARD_DEVIATION 1.73 | 67 years STANDARD_DEVIATION 6.24 | 72.8 years STANDARD_DEVIATION 9.62 | 69.9 years STANDARD_DEVIATION 7.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 6 Participants | 10 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 2 / 3 | 5 / 6 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 1 / 6 |
Outcome results
Primary
Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose
Time frame: Through the 21 day interval after the first dose of vaccine
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | Dose Limiting Toxicity Observed | 0 Participants |
| Cohort 1 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | No Dose Limiting Toxicity Observed | 3 Participants |
| Cohort 1 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | Maximum Tolerated Dose Reached | 0 Participants |
| Cohort 2 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | Dose Limiting Toxicity Observed | 0 Participants |
| Cohort 2 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | No Dose Limiting Toxicity Observed | 3 Participants |
| Cohort 2 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | Maximum Tolerated Dose Reached | 0 Participants |
| Cohort 3 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | No Dose Limiting Toxicity Observed | 6 Participants |
| Cohort 3 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | Maximum Tolerated Dose Reached | 0 Participants |
| Cohort 3 | Safety Assessed by Development of Adverse Events and Dose-limiting Toxicity to Determine Maximum Tolerated Dose | Dose Limiting Toxicity Observed | 0 Participants |
Secondary
Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events
Time frame: Through study completion, an average of 3 months. Patients were able to continue on treatment with one patient receiving approximately 15 months of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events | Subjects with no treatment related adverse events observed | 2 Participants |
| Cohort 1 | Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events | Subjects with treatment related adverse events observed | 1 Participants |
| Cohort 2 | Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events | Subjects with no treatment related adverse events observed | 1 Participants |
| Cohort 2 | Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events | Subjects with treatment related adverse events observed | 2 Participants |
| Cohort 3 | Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events | Subjects with no treatment related adverse events observed | 6 Participants |
| Cohort 3 | Safety Assessed by Administration Site Reactions, Abnormal Laboratory Values and/or Adverse Events | Subjects with treatment related adverse events observed | 0 Participants |