Clinical Trials /

The Safety and Tolerability of PGV001-based Personalized Multi-peptide Vaccines in the Adjuvant Setting.

NCT05010200

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: The Safety and Tolerability of PGV001-based Personalized Multi-peptide Vaccines in the Adjuvant Setting.
  • Official Title: Phase I, Open-label, Single-center Proof of Concept Study 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 Prostate Cancer, in the Adjuvant Setting

Clinical Trial IDs

  • ORG STUDY ID: Study 20-02159
  • SECONDARY ID: PRMC 20-027
  • NCT ID: NCT05010200

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
PGV-001Cohort 1 - Primary treatment cohort
Poly-ICLCCohort 1 - Primary treatment cohort
CDX-301Cohort 2 - Secondary treatment cohort

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 - Primary treatment cohortExperimentalPatients receive the personalized genomic vaccine (PGV) and Poly-ICLC.
  • PGV-001
  • Poly-ICLC
Cohort 2 - Secondary treatment cohortExperimentalPatients receive the personalized genomic vaccine (PGV) and Poly-ICLC, and CDX-301
  • PGV-001
  • Poly-ICLC
  • CDX-301
Cohort 3 - Expansion treatment cohortExperimentalAn expansion cohort if the treatment of all 3 together has not triggered a safety stopping event.
  • PGV-001
  • Poly-ICLC
  • CDX-301

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of adverse events
Time Frame:37 days
Safety Issue:
Description:Adverse events will be measured by severity of Adverse events with toxicity grading defined by Cancer Therapy Evaluation Program's (CTEP) v5.0 of National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scale .

Secondary Outcome Measures

Measure:Change in immune cell subsets
Time Frame:37 days
Safety Issue:
Description:Changes in immune cell subsets to compare immune responses at baseline to prostate antigens and viruses with immune responses obtained after treatment with the vaccine combination
Measure:Change in immune cell subsets
Time Frame:191 days
Safety Issue:
Description:Changes in immune cell subsets to compare immune responses at baseline to prostate antigens and viruses with immune responses obtained after treatment with the vaccine combination
Measure:Change in immune cell subsets
Time Frame:365 days
Safety Issue:
Description:Changes in immune cell subsets to compare immune responses at baseline to prostate antigens and viruses with immune responses obtained after treatment with the vaccine combination
Measure:Change in the frequency of vaccine epitope-specific T lymphocyte populations
Time Frame:37 days
Safety Issue:
Description:Change in the frequency of vaccine epitope-specific T lymphocyte populations in post-treatment peripheral blood compared to peripheral blood obtained prior to the start of vaccination.
Measure:Change in the frequency of vaccine epitope-specific T lymphocyte populations
Time Frame:191 days
Safety Issue:
Description:Change in the frequency of vaccine epitope-specific T lymphocyte populations in post-treatment peripheral blood compared to peripheral blood obtained prior to the start of vaccination.
Measure:Change in the frequency of vaccine epitope-specific T lymphocyte populations
Time Frame:365 days
Safety Issue:
Description:Change in the frequency of vaccine epitope-specific T lymphocyte populations in post-treatment peripheral blood compared to peripheral blood obtained prior to the start of vaccination.
Measure:Radiographic free survival
Time Frame:10 years
Safety Issue:
Description:Radiographic free survival (RFS) by Kaplan-Meier (KM) method.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ashutosh Kumar Tewari

Last Updated

August 18, 2021