This proof of concept study is designed to test the safety and tolerability of PGV001-based
personalized multi-peptide vaccines in combination with CDX-301 in subjects with a history of
aggressive prostate cancer, in the tumor free adjuvant setting.
This proof of concept study is designed to test the safety and tolerability of PGV001-based
personalized multi-peptide vaccines in combination with CDX-301 in subjects with a history of
aggressive prostate cancer, in the tumor free adjuvant setting.
This study will also assess the capacity of PGV001-based a multi-peptide therapeutic vaccines
to produce a robust tumor antigen-specific T lymphocytic response in the peripheral
circulation when combined with CDX-301, and it will expand the collective body of knowledge
regarding the identification, selection and use of mutation-derived tumor antigens for
personalized immunotherapy in prostate cancer patients.
The purpose of the proposed trial will be to assess the following hypothesis:
Mutation-derived tumor antigens (MTA) may arise as a result of somatic non-synonymous
variations-including nucleotide substitutions, as well as small insertions and
deletions-which occur during tumorigenesis. Somatic mutations may be characterized through
the use of high-throughput sequencing technologies, and the resulting sequence data used to
identify TSA. Sequence data can inform the design of patient-specific immune-based therapies,
which may be capable of inducing quantitative changes in the concentration of circulating
antigen-specific T lymphocytes directed against TSA, which may in-turn lead to
immune-mediated elimination of residual malignant cells.
Inclusion Criteria:
To be enrolled a subject must meet the following criteria:
- The subject must have a histologically proven diagnosis of adenocarcinoma of prostate
- The subject should have any one of:
1. PSA persistence post surgery (defined as a PSA value that fails to become
undetectable) by six weeks post treatment,
2. Biochemical recurrence (defined as a PSA value ≥ 0.2ng/ml),
3. An elevated PSA with a doubling time of > 3 months,
4. Or an estimated risk of biochemical recurrence within 5 years of 30% or more as
assessed by decipher™ report (decipher score of ≥0.3).
- At the time of treatment, the subjects must have completed radical prostatectomy (rp),
all additional s.o.c therapies and be clinically tumor free as defined by s.o.c
imaging studies
- Written informed consent obtained prior to any study procedure.
- The subject must be able to provide the necessary tissue sample for sequencing, either
by surgical resection or open-surgical or core biopsy sampling of the primary tumor
- This requirement may be satisfied by providing an archival tissue sample that has been
stored in rna later, flash-frozen, or under other rna/dna preserving conditions from
an earlier resection.
- This requirement may also be satisfied by providing rna/dna sequencing from a CLIA
certified genomic sequencing laboratory.
- Before administration of the investigational product, the following time must have
elapsed:
1. At least (4) weeks post general anesthesia
2. At least seventy-two (72) hours post local/epidural anesthesia
3. The subject must complete all prior systemic chemotherapy therapy, and all
adverse events have either returned to baseline or have stabilized at least four
(4) weeks prior to administration of the investigational product.
4. The subject must complete all prior systemic radiation therapy at least four (4)
weeks prior to administration of the investigational product. The subject must
not have received a radiopharmaceutical within eight (8) weeks prior to the
administration of the investigational product.
5. The subject may continue hormonal therapy (e.g. Anti-androgens) during the study.
6. Subjects may have a detectable or rising PSA provided there is no radiographic
evidence of metastatic disease. For patients with a rising PSA, the doubling time
should be >3 months.
9. The subject must have a life expectancy greater than twelve (12) months at the
time of screening as assessed by the treating physician.
- The subject must have a performance status of 0-1 as determined by criteria set
forward by the eastern cooperative oncology group243.
- The subject must have at the time of screening acceptable hematologic, hepatic, and
renal function, defined by the following:
1. Absolute neutrophil count > 1000/mm3
2. Platelet count > 50,000/mm3,
3. Creatinine < 2.5 mg/dl,
4. Total bilirubin ≤ 1.5 mg/dl, (except in patients with gilbert syndrome who can
have total bilirubin < 3.0 mg/dl)
5. Transaminases < 2 times above the upper limits of the institutional normal.
6. INR<2 if off of anticoagulation. Patients on anticoagulation therapy with an
INR>2 may be enrolled at the discretion of the investigator if they have not had
any episodes of severe hemorrhage.
- Adequate venous access (for leukapheresis and blood draws)
- The subject must be male 18 years of age or older.
- The subject must be deemed competent to give informed consent.
- The subject must agree to use a condom and another effective method of birth control
if he is having sex with a woman of childbearing potential or agrees to use a condom
if he is having sex with a woman who is pregnant.
Exclusion Criteria:
Potential subjects who meet any of the following criteria will not be included in the
study:
- The subject has metastatic disease at the time of treatment.
- Patients with history of AML or tumors with known Flt3 mutations/amplifications.
- The subject has a history of unrelated neoplastic disease, which has been deemed
active within thirty-six (36) months of the screening evaluation, with the exception
of the following:
1. Non-invasive non-melanoma skin cancer such as superficial basal cell carcinoma or
squamous cell carcinoma.
2. Subjects with tumors of the prostate with a combined Gleason Score ≤ 7
3. Patients with other completely resected malignancies in the prior three years and
no evidence of disease will be evaluated on a case-by-case basis with eligibility
determined based on discussion with the Principal Investigator.
- The subject has a prior history of unrelated neoplastic disease and has received
systemic therapy for the secondary malignancy within the twelve (12) month period
preceding the screening evaluation.
- The subject has a history of Human Immunodeficiency Virus/Acquired Immunodeficiency
Syndrome (HIV/AIDS), chronic active hepatitis B or hepatitis C with positive PCR.
- The subject has a history of, or is reasonably suspected to meet criteria for the
diagnosis of a known congenital or acquired disorder causing systemic
immunosuppression; or the subject is currently receiving any drug or supplement which
is known to be associated with systemic immune suppression including those drugs which
are prescribed for solid organ or stem cell transplant, autoimmune/inflammatory
disorders, or other related medical conditions.
- The subject has a history of, or is reasonably suspected to meet criteria for the
diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder
with the exception of:
1. Vitiligo
2. Hypothyroidism
- The subject has a history of anaphylaxis or other serious adverse reactions relating
to administration of any components of the investigational product.
- The subject has a history of serious allergic reaction to any substance, resulting in
hospitalization or requiring other emergent medical attention.
- The subject has a history of advanced cardiac, hepatic or renal disease or other
chronic illness.
- The subject has been diagnosed and treated at an external facility, and the resulting
tissue specimen is of insufficient quality such that it precludes clinical sequencing
or any other necessary study procedure, and the subject is unwilling to undergo an
additional biopsy procedure.
- Previous treatment with therapeutic cancer vaccine of any type
- The subject is less than eighteen (18) years of age, or otherwise unable to give
informed consent due to minor status.
- The subject is a prisoner, as defined by [45 CFR 46.303(c)].
- The subject is cognitively impaired, and unable to give informed consent.