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CompletedNCT01519817Updated Jan 29, 2018Results posted

Cancer Vaccine Targeting Brachyury Protein in Tumors

A Phase 1 interventional study of GI-6301 (Yeast Brachyury Vaccine) in Neoplasms, Malignant Solid Tumors and Colon Neoplasms, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2018-01-29.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
34
Allocation
Not applicable
Ages
18 Years to 100 Years
Sex
All
01

Study summary

Background:

  • Cancer vaccines are being developed to help teach the body's immune system to attack and destroy cancer cells. A new vaccine being tested targets Brachyury protein. This protein is present in some tumor cells, and it can help tumor cells spread to other parts of the body. Researchers want to see whether the new Brachyury protein vaccine can help treat people with advanced carcinomas.

Objectives:

  • To test the safety and effectiveness of a cancer vaccine that targets Brachyury protein in tumor cells.

Eligibility:

  • Individuals at least 18 years of age who have advanced cancers that have not responded or are no longer responding to standard treatments.
  • Because the vaccine is made with yeast, people with yeast allergies will not be eligible.

Design:

  • Participants will be screened with a medical history and physical exam. Imaging studies will be used to examine the cancer. Heart and thyroid function tests will be conducted. Blood and urine samples will also be collected.
  • Participants will receive vaccine injections every 2 weeks, for a total of seven visits. After seven visits, if the cancer has shrunk or stopped growing, participants will continue to have the vaccine about once a month.
  • Treatment will be monitored with frequent blood tests and imaging studies. Other tests will be given as directed by the study doctors. Some participants will have apheresis to collect additional blood cells for study.
  • Participants will continue to receive the vaccine as long the tumor does not start growing again and there are no serious side effects....
Read the detailed description

Background:

  • Vaccines based on recombinant heat inactivated yeast have been shown to be immunogenic and well tolerated in animals and humans.
  • Using a computer-based differential display analysis tool to conduct global comparison of expressed sequence tag (EST) clusters in the Unigene database, the gene encoding for the transcription factor Brachyury was identified as highly represented in tumor-derived libraries and rarely observed in normal tissue-derived libraries. By using reverse-transcription followed by polymerase chain reaction (RT-PCR), investigators in the LTIB have identified the overexpression of Brachyury in gastrointestinal, bladder, kidney, ovary, uterus, and testicular carcinomas. Similar studies also found over-expression of Brachyury mRNA in cell lines of lung, colon and prostate cancers, but not in the majority of normal tissues tested, with the exception of expression in the testis, thyroid and low levels of expression in B cells pooled from multiple normal donors.
  • Brachyury is a member of the T-box family of transcription factors, characterized by a highly conserved DNA-binding domain designated as T-domain. Data indicates that the transcription factor Brachyury confers on the tumor cells a mesenchymal phenotype, as well as migratory and invasive abilities and enhances tumor cell progression.
  • A murine model of MC38 cells engineered to over express human Brachyury gene has demonstrated increased metastatic potential of Brachyury over-expressing MC38 cells.
  • Brachyury specific T cells can lyse human cancer cells expressing Brachyury in an MHC restricted manner.
  • GI-6301 (Yeast-Brachyury vaccine) has been tested in vitro and in the mouse model. These studies showed Brachyury-specific T cell responses and decreased metastasis in mice treated with vaccine.
  • An ongoing study of a Hepatitis B vaccine (GS-4774) using the yeast platform (heat killed Saccharomyces cerevisiae) indicated safety of 80 YU dose (4 injection sites at 20 YU injections per site).

Objectives:

-The primary objectives are to:

  • Determine the safety and tolerability of escalating doses of GI-6301 (Yeast-Brachyury vaccine) a heat-killed yeast-based vaccine
  • Determine in an expanded cohort if a significant change in Brachyury specific T cells will be detectable post vaccine.

Eligibility:

  • Adults with histologically proven metastatic or locally advanced solid tumors for which standard curative or palliative measures are no longer effective. Efforts will be made, as much as possible, to enroll patients with tumor types with known increased expression of Brachyury (such as lung, breast, ovarian, prostate, colorectal, pancreatic or chordoma).
  • Adequate organ function as defined by liver, kidney, and hematologic laboratory testing.
  • Patients with acquired immune defects, systemic autoimmune disease, concurrent use of steroids, pericardial mass > 1 cm, chronic infections, concurrent tricyclic antidepressant therapy, or allergy to yeast or yeast-based products will be excluded.

Design:

  • This is an open label, phase I trial with sequential dose escalation cohorts of patients (3-6 patients per dose cohort) for 3 doses of GI-6301 (Yeast-Brachyury vaccine).
  • GI-6301 (Yeast-Brachyury vaccine) will be administered subcutaneously at 4 sites biweekly for 7 visits (day 1, 15, 29, 43, 57, 71, 85), then monthly until patients meet off-study criteria

(patients who have been on study for one year or more and have had stable disease or better (PR, CR) have the option to receive vaccine once every 3 months instead of monthly).

  • All patients on a given dose level will have completed 28 days on-study without DLT before enrollment can begin on the next dose level or on the expansion phase (see statistical analysis section).
  • Expansion Phase: 10 additional patients will be enrolled on the MTD dose level (or the highest dose level explored in the event that a true MTD is not reached), receiving the same treatment regimen, to assess for immunologic responses and clinical responses.
  • Amended dose escalation: 10 patients will be enrolled at an additional dose level (80 YU per dose, 4 injection sites at 20 YU per site) to determine the safety of this dose level.
  • Up to 33 total patients may be required to complete enrollment of this study.
02

Conditions studied

  • Neoplasms
  • Malignant Solid Tumors
  • Colon Neoplasms
  • Adenocarcinoma

Keywords

  • Vaccine Therapy
  • Dose-Limiting Toxicity
  • Maximum Tolerated Dose
  • Clinical Response
  • Immune Response
  • Cancer
  • Solid Tumor
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 34 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Participants must meet the following criteria for participation:

  • Diagnosis: Patients must have histologically confirmed malignancy by the Laboratory of Pathology, National Cancer Institute (NCI), that is metastatic or unresectable locally advanced malignant solid tumor. In the case of Chordoma, unresectable, locally recurrent, or metastatic tumors are acceptable for enrollment, given that this represents incurable disease. Efforts will be made, as much as possible, to enroll patients with tumor types with known increased expression of Brachyury (such as lung, breast, ovarian, prostate, colorectal, pancreatic, or chordoma).
  • Patients may have disease that is measurable or non-measurable but evaluable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry (Karnofsky greater than or equal to 70)
  • Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of Yeast Brachyury vaccine in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  • Prior Therapy: Completed or had disease progression on at least one prior line of diseaseappropriate therapy for metastatic disease, or not be a candidate for therapy of proven efficacy for their disease.

  • Patients must have normal organ and marrow function as defined below:

    • Serum creatinine 1.5 times upper limit of normal OR creatinine clearance on a 24-h urine collection of 60 mL/min.
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 times the upper limits of normal.
    • Total bilirubin less than or equal to 1.5 times upper limit of normal OR in patients with Gilbert's syndrome, a total bilirubin 3.0.
    • Hematological eligibility parameters (within16 days of starting therapy):
    • Granulocyte count 1,500/mm(3)
    • Platelet count 100,000/m(3)
    • Patients must have baseline pulse oximetry > 90% on room air.
  • Recovered completely (Grade 1 or baseline) from any reversible toxicity associated with recent therapy. Typically this is 3 4 weeks for patients who most recently received cytotoxic therapy, except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery.
  • There should be a minimum of 2 weeks from any prior chemotherapy, immunotherapy and/or radiation.
  • Prior immune therapy is allowed.
  • Men and women of child-bearing potential must agree to use effective birth control or abstinence during and for a period of 4 months after the last vaccination therapy.
  • Patients with prostate cancer must continue to receive gonadotropin-releasing hormone (GnRH) agonist therapy (unless orchiectomy has been done). If a patient has refused GnRH therapy, they may be enrolled on a dose level for which the safety has already been determined.
  • Patients with estrogen-receptor positive (ER+) breast cancer being treated with adjuvant hormonal therapy (selective estrogen receptor modulator or aromatase inhibitor) who have rising tumor markers as evidence of disease progression or metastatic disease on scans may continue on hormonal therapy while being treated with vaccine.
  • Patients must be negative for yeast allergy skin test
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

EXCLUSION CRITERIA:

Patients with any of the following will not be eligible for participation in this study:

  • Patients should have no evidence of immune dysfunction as listed below.
  • Human immunodeficiency virus (HIV) positivity due to the potential for decreased immune response to the vaccine.
  • Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity. However, patients with vitiligo, diabetes mellitus, and hashimoto s thyroiditis on appropriate replacement therapy may be

enrolled.

--Concurrent use of systemic steroids, except for physiologic doses of systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Limited doses of systemic steroids (e.g., in patients with exacerbations of reactive airway disease or to prevent intravenous (IV) contrast allergic reaction or anaphylaxis in patients who have known contrast allergies) are allowed.

  • History of allergy or untoward reaction to yeast-based products (any hypersensitivity to yeast-based products will be excluded).
  • Pregnant or breast-feeding women, due to the unknown effects of the Yeast Brachyury vaccine on the fetus or infant.
  • Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis.
  • Untreated brain metastases (or local treatment of brain metastases within the last 6 months) and or spinal cord metastasis.
  • Patients with pericardial masses >1 cm will be excluded.
  • Concurrent chemotherapy. (However, the following anti-tumor therapies will be allowed: Trastuzumab for human epidermal growth factor receptor 2 (HER2+) breast cancer and hormonal therapy for breast (e.g., selective estrogen receptor modulators, aromatase inhibitors) and prostate cancer (e.g., GnRH antagonists/agonists or antagonists and androgen receptor antagonists).
  • Chronic hepatitis infection, including B and C, because potential immune impairment caused by these disorders may diminish the effectiveness of this immunologic therapy.
  • Patients requiring continuous tricyclic antidepressant therapy should be excluded due to the interference with the yeast skin test in creating false negative test results.
  • Participation in another interventional clinical trial within 28 days before start of study treatment.
  • Any significant disease that, in the opinion of the investigator, may impair the patient s tolerance of study treatment.
  • Significant dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
34 participants (actual)

Study arms

  • Experimental
    Yeast-Brachyury vaccine

    Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.

    Biological: GI-6301 (Yeast Brachyury Vaccine)

Interventions

  • BiologicalGI-6301 (Yeast Brachyury Vaccine)

    GI-6301 is a heat-killed, recombinant yeast-based vaccine engineered to express the transcription factor, Brachyury. The Brachyury gene is used to transfect the parental yeast strain (S. cerevisiae W303 - a haploid strain with known mutations from wildtype yeast) to produce the final recombinant vaccine product.

    Also known as: Yeast-Brachyury vaccine

06

What researchers measure

Primary outcomes

  1. Number of Participants With Brachyury-Specific T-cell Responses

    A fluorescense activated cell sorting (FACS)-based assay for cluster of differentiation 4 (CD4) or cluster of differentiation 8 (CD8) T-cells expressing the cytokines interferon (IFN) gamma, interleukin 2 (IL2), and tumor necrosis factor (TNF) alpha, and/or cluster of differentiation 107a (CD107a) (a marker for lytic potential) was used to determine the numbers of participants showing development or enhancement of the level of brachyury-specific T-cells after vaccination.

    Time frame: Baseline (pre-vaccination) and approximately day 84 (after 6 vaccinations)

  2. Count of Participants With Adverse Events of Escalating Doses of Yeast Brachyury ( GI- 6301) Vaccine

    Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. A non-serious adverse event is any untoward medical occurrence.

    Time frame: 4 years and 25 days

Secondary outcomes

  1. Number of Participants With a Clinical Benefit Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)

    Clinical benefit is defined as partial response (PR) or stable disease (SD) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial response is ≥30% decrease in the sum of greatest diameters/no new lesions. Progressive disease is ≥20% increase in the sum of greatest diameters/new lesions. Stable disease does not meet criteria for complete response (disappearance of all lesions; no new lesions), partial response, or progressive disease.

    Time frame: 3 and 5 months restaging

  2. Changes in Immune Cell Subsets in Peripheral Blood Mononuclear Cells (PBMC)

    Blood samples will be collected via apheresis and analyzed by multicolor flow cytometry in PBMCs for cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK), Natural Killer T (NKT), conventional dendritic cell (cDC), plasmacytoid dendritic cell (pDC), myeloid-derived suppressor cell (MDSC), Tregs, CD4 central memory (CD4 CM), CD4 effector memory (CD4 EM), CD4 terminal effector memory (CD4 EMRA), CD4 naïve, CD8 CM, CD8 EM, CD8 EMRA, and CD8 naïve cells. Significance of changes in immune cells was determined by p value (Wilcoxon test) and the median and interquartile range of data.

    Time frame: Pre (Baseline) and Day 85 after 6 vaccinations

  3. Changes in Serum Levels of Cytokines

    Blood samples were collected and changes in serum levels of cytokines interferon gamma (IFNg), Interleukin 10 (IL-10), Interleukin 12 (IL-12)p70, Interleukin 1b (IL-1b), Interleukin 2 (IL-2), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and tumor necrosis factor (TNF) were assessed by the multiplexed mesoscale assay. Significance of changes in serum levels of cytokines was determined by p value (Wilcoxon test) and the median and interquartile range of data.

    Time frame: Pre (Baseline) and Day 85 after 6 vaccinations

  4. Changes in Soluble Cluster of Differentiation 27 (sCD27)

    Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27 was determined by p value (Wilcoxon test) and the median and interquartile range of data.

    Time frame: Pre (Baseline) and Day 85 after 6 vaccinations

  5. Median Ratio of Soluble Cluster of Differentiation 27:40L (sCD27:sCD40L)

    Blood samples were collected and changes in serum levels of the ratio of soluble sCD27:sCD40L was assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27:sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.

    Time frame: Pre (Baseline) and Day 85 after 6 vaccinations

  6. Changes in Soluble Cluster of Differentiation 40L (sCD40L)

    Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.

    Time frame: Pre (Baseline) and Day 85 after 6 vaccinations

07

Results

Posted Jul 31, 2017

Participant flow

Participant flow — Overall Study
Milestone4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Started431611
Completed331610
Not completed1001
Withdrew: Withdrawal by subject1000
Withdrew: Off study due to infection0001

Outcome measures

PrimaryNumber of Participants With Brachyury-Specific T-cell Responses

A fluorescense activated cell sorting (FACS)-based assay for cluster of differentiation 4 (CD4) or cluster of differentiation 8 (CD8) T-cells expressing the cytokines interferon (IFN) gamma, interleukin 2 (IL2), and tumor necrosis factor (TNF) alpha, and/or cluster of differentiation 107a (CD107a) (a marker for lytic potential) was used to determine the numbers of participants showing development or enhancement of the level of brachyury-specific T-cells after vaccination.

Time frame:
Baseline (pre-vaccination) and approximately day 84 (after 6 vaccinations)
Reported as:
Count of participants · Participants
Number of Participants With Brachyury-Specific T-cell Responses
Participants4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
CD107a + CD4 T-cell response1041
IFN gamma + CD4 T-cell response1032
IL2 + CD4 T-cell response0033
TNF alpha + CD4 T-cell response0162
CD107a + CD8 T-cell response0034
IFN gamma + CD8 T-cell response0032
IL2 + CD8 T-cell response0001
TNF alpha + CD8 T-cell response0023
Any T-cell response1187
PrimaryCount of Participants With Adverse Events of Escalating Doses of Yeast Brachyury ( GI- 6301) Vaccine

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. A non-serious adverse event is any untoward medical occurrence.

Time frame:
4 years and 25 days
Reported as:
Count of participants · Participants
Count of Participants With Adverse Events of Escalating Doses of Yeast Brachyury ( GI- 6301) Vaccine
Participants4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Count of Participants With Adverse Events of Escalating Doses of Yeast Brachyury ( GI- 6301) Vaccine431610
SecondaryNumber of Participants With a Clinical Benefit Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)

Clinical benefit is defined as partial response (PR) or stable disease (SD) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial response is ≥30% decrease in the sum of greatest diameters/no new lesions. Progressive disease is ≥20% increase in the sum of greatest diameters/new lesions. Stable disease does not meet criteria for complete response (disappearance of all lesions; no new lesions), partial response, or progressive disease.

Time frame:
3 and 5 months restaging
Reported as:
Count of participants · Participants
Number of Participants With a Clinical Benefit Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Participants4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Stable disease at 3 months3086
Stable disease at 5 months2043
Partial response at 3 months0000
Partial response at 5 months0010
Progressive disease at 3 months1385
Progressive disease at 5 months1030
SecondaryChanges in Immune Cell Subsets in Peripheral Blood Mononuclear Cells (PBMC)

Blood samples will be collected via apheresis and analyzed by multicolor flow cytometry in PBMCs for cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK), Natural Killer T (NKT), conventional dendritic cell (cDC), plasmacytoid dendritic cell (pDC), myeloid-derived suppressor cell (MDSC), Tregs, CD4 central memory (CD4 CM), CD4 effector memory (CD4 EM), CD4 terminal effector memory (CD4 EMRA), CD4 naïve, CD8 CM, CD8 EM, CD8 EMRA, and CD8 naïve cells. Significance of changes in immune cells was determined by p value (Wilcoxon test) and the median and interquartile range of data.

Time frame:
Pre (Baseline) and Day 85 after 6 vaccinations
Reported as:
Median · percentage of PBMC
Changes in Immune Cell Subsets in Peripheral Blood Mononuclear Cells (PBMC)
percentage of PBMC4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Median CD4 Pre37.70 (24.11 to 46.36)43.57 (40.26 to 46.87)29.30 (24.65 to 39.77)33.58 (26.84 to 39.92)
Median CD4 d8538.61 (24.44 to 47.73)33.44 (33.37 to 33.52)34.29 (25.56 to 37.44)27.99 (25.85 to 39.38)
Median CD8 Pre15.87 (8.26 to 16.86)14.77 (3.49 to 26.04)15.96 (10.76 to 19.48)13.76 (10.31 to 19.77)
Median CD8 d8515.67 (9.102 to 16.57)13.63 (4.123 to 23.14)15.42 (10.96 to 22.44)16.02 (10.57 to 25.5)
Median B cells Pre7.05 (6.19 to 10.07)11.02 (9.92 to 12.11)8.97 (3.54 to 12.13)7.82 (3.13 to 12.07)
Median B cells d856.93 (6.16 to 10.58)9.78 (7.95 to 11.62)9.10 (5.07 to 12.17)8.77 (3.78 to 10.72)
Median Natural Killer (NK) Pre5.21 (4.14 to 6.94)6.57 (3.27 to 9.87)5.72 (3.13 to 8.51)5.89 (4.59 to 9.14)
Median Natural Killer (NK) d855.72 (4.03 to 7.39)8.41 (5.50 to 11.31)4.22 (3.97 to 10.07)9.14 (5.95 to 11.4)
Median Natural Killer T cell (NKT) Pre1.00 (0.65 to 4.21)1.70 (0.46 to 2.94)1.27 (0.62 to 2.81)2.24 (0.59 to 4.39)
Median Natural Killer T cell (NKT) d851.25 (0.67 to 4.75)2.46 (0.51 to 4.40)1.19 (0.58 to 3.15)2.53 (0.77 to 5.86)
Median cDC Pre0.25 (0.14 to 0.28)0.14 (0.11 to 0.17)0.23 (0.20 to 0.37)0.17 (0.16 to 0.35)
Median cDC d850.18 (0.14 to 0.23)0.17 (0.16 to 0.19)0.21 (0.18 to 0.34)0.19 (0.09 to 0.23)
Median pDC Pre0.25 (0.20 to 0.37)0.17 (0.09 to 0.24)0.23 (0.17 to 0.36)0.23 (0.11 to 0.31)
Median pDC d850.32 (0.27 to 0.38)0.26 (0.08 to 0.44)0.27 (0.18 to 0.35)0.23 (0.14 to 0.40)
Median MDSC Pre10.98 (2.96 to 19.19)8.53 (4.30 to 12.76)8.47 (5.98 to 14.54)13.73 (5.41 to 17.61)
Median MDSC d8511.41 (4.82 to 18.78)10.78 (5.98 to 15.58)7.55 (4.95 to 12.16)12.77 (6.64 to 14.23)
Median Treg Pre0.77 (0.66 to 0.90)0.90 (0.68 to 1.13)1.25 (0.73 to 1.74)1.07 (0.55 to 1.60)
Median Treg d850.81 (0.78 to 1.03)0.80 (0.42 to 1.17)1.12 (0.83 to 1.71)1.00 (0.45 to 1.41)
Median CD4 EM Pre10.58 (8.47 to 12.73)12.09 (9.67 to 14.51)13.14 (10.67 to 14.82)11.31 (8.49 to 15.97)
Median CD4 EM d858.92 (7.49 to 13.48)10.72 (9.20 to 12.25)12.50 (11.33 to 13.63)9.76 (7.21 to 15.68)
Median CD4 CM Pre17.29 (8.59 to 21.10)23.20 (12.62 to 33.79)12.36 (9.16 to 17.44)12.07 (7.52 to 16.56)
Median CD4 CM d8518.80 (9.75 to 24.37)16.51 (10.97 to 22.06)12.78 (10.53 to 17.98)11.36 (6.00 to 14.40)
Median CD4 EMRA Pre0.32 (0.28 to 1.96)0.68 (0.21 to 1.15)0.34 (0.26 to 0.90)0.28 (0.21 to 1.04)
Median CD4 EMRA d850.34 (0.26 to 0.70)0.83 (0.24 to 1.43)0.28 (0.23 to 0.56)0.38 (0.21 to 1.75)
Median CD4 naive Pre10.28 (4.23 to 12.36)7.57 (3.23 to 11.91)3.78 (2.47 to 6.90)4.49 (2.56 to 10.22)
Median CD4 naive d858.48 (4.14 to 12.76)5.41 (2.08 to 8.73)3.99 (3.49 to 7.51)6.08 (3.15 to 9.55)
Median CD8 EM Pre3.20 (2.33 to 6.85)2.70 (1.54 to 3.86)7.19 (4.45 to 8.92)5.23 (4.21 to 7.64)
Median CD8 EM d853.44 (2.85 to 6.87)3.33 (2.61 to 4.06)6.60 (4.12 to 10.78)6.11 (3.91 to 7.30)
Median CD8 CM Pre1.03 (0.61 to 2.70)1.05 (0.80 to 1.30)1.16 (0.56 to 1.48)1.00 (0.53 to 1.38)
Median CD8 CM d851.31 (0.81 to 2.43)0.86 (0.53 to 1.19)0.95 (0.80 to 1.44)0.88 (0.32 to 1.26)
Median CD8 EMRA Pre3.01 (1.22 to 8.46)2.51 (0.63 to 4.39)2.60 (1.36 to 9.95)5.81 (2.26 to 8.75)
Median CD8 EMRA d852.84 (1.40 to 7.35)3.24 (0.69 to 5.80)3.31 (1.14 to 10.71)5.06 (3.11 to 10.83)
Median CD8 naive Pre3.47 (2.50 to 5.60)8.51 (0.53 to 16.49)2.43 (0.92 to 5.25)3.71 (2.86 to 5.92)
Median CD8 naive d853.28 (2.58 to 6.21)6.20 (0.30 to 12.09)3.12 (1.00 to 5.82)3.44 (2.06 to 5.45)
Statistical analysis
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.5221 (The reported p-value is representative of the changes in levels of all CD4 cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.25 (The reported p-value is representative of the changes in levels of CD4 cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.50 (The reported p-value is representative of the changes in levels of CD4 cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.16 (The reported p-value is representative of the changes in levels of CD4 cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.8665 (The reported p-value is representative of the changes in levels of all CD8 cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.88 (The reported p-value is representative of the changes in levels of all CD8 cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.84 (The reported p-value is representative of the changes in levels of CD8 cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.57 (The reported p-value is representative of the changes in levels of CD8 cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.3052 (The reported p-value is representative of the changes in levels of all B cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of B cells at dose level 1.)The reported p-value is representative of the changes in levels of B cells at dose level 1.
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.13 (The reported p-value is representative of the changes in levels of B cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.65 (The reported p-value is representative of the changes in levels of B cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.0698 (The reported p-value is representative of the changes in levels of all NK cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.63 (The reported p-value is representative of the changes in levels of NK cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.74 (The reported p-value is representative of the changes in levels of NK cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.13 (The reported p-value is representative of the changes in levels of NK cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.0127 (The reported p-value is representative of the changes in levels of all NKT cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.63 (The reported p-value is representative of the changes in levels of NKT cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.41 (The reported p-value is representative of the changes in levels of NKT cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.07 (The reported p-value is representative of the changes in levels of NKT cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.0654 (The reported p-value is representative of the changes in levels of all cDC cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.38 (The reported p-value is representative of the changes in levels of cDC cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.21 (The reported p-value is representative of the changes in levels of cDC cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.16 (The reported p-value is representative of the changes in levels of cDC cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.0457 (The reported p-value is representative of the changes in levels of all pDC cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.63 (The reported p-value is representative of the changes in levels of pDC cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.55 (The reported p-value is representative of the changes in levels of pDC cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.13 (The reported p-value is representative of the changes in levels of pDC cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.7114 (The reported p-value is representative of the changes in levels of all MDSC cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of MDSC cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.38 (The reported p-value is representative of the changes in levels of MDSC cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.91 (The reported p-value is representative of the changes in levels of MDSC cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.2666 (The reported p-value is representative of the changes in levels of all Treg cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.88 (The reported p-value is representative of the changes in levels of Treg cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.45 (The reported p-value is representative of the changes in levels of Treg cells at dose level 1.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.36 (The reported p-value is representative of the changes in levels of Treg cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.0076 (The reported p-value is representative of the changes in levels of all CD4 EM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.38 (The reported p-value is representative of the changes in levels of CD4 EM cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.22 (The reported p-value is representative of the changes in levels of CD4 EM cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.10 (The reported p-value is representative of the changes in levels of CD4 EM cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.7144 (The reported p-value is representative of the changes in levels of all CD4 CM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.13 (The reported p-value is representative of the changes in levels of CD4 CM cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.06 (The reported p-value is representative of the changes in levels of CD4 CM cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.13 (The reported p-value is representative of the changes in levels of CD4 CM cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.3741 (The reported p-value is representative of the changes in levels of all CD4 EMRA cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.63
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.13 (The reported p-value is representative of the changes in levels of CD4 EMRA cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of CD4 EMRA cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.3386 (The reported p-value is representative of the changes in levels of all CD4 naive cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.88 (The reported p-value is representative of the changes in levels of CD4 naive cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.0215 (The reported p-value is representative of the changes in levels of CD4 naive cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.65 (The reported p-value is representative of the changes in levels of CD4 naive cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.5076 (The reported p-value is representative of the changes in levels of all CD8 EM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.63 (The reported p-value is representative of the changes in levels of CD8 EM cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.68 (The reported p-value is representative of the changes in levels of CD8 EM cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.73 (The reported p-value is representative of the changes in levels of CD8 EM cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.6577 (The reported p-value is representative of the changes in levels of all CD8 CM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.88 (The reported p-value is representative of the changes in levels of CD8 CM cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.74 (The reported p-value is representative of the changes in levels of CD8 CM cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.20 (The reported p-value is representative of the changes in levels of CD8 CM cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.6295 (The reported p-value is representative of the changes in levels of all CD8 EMRA cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.63 (The reported p-value is representative of the changes in levels of CD8 EMRA cells at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = >0.999 (The reported p-value is representative of the changes in levels of CD8 EMRA cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.36 (The reported p-value is representative of the changes in levels of CD8 EMRA cells at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.8314 (The reported p-value is representative of the changes in levels of all CD8 naive cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.63
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.64 (The reported p-value is representative of the changes in levels of CD8 naive cells at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.30 (The reported p-value is representative of the changes in levels of CD8 naive cells at dose level 4.)
SecondaryChanges in Serum Levels of Cytokines

Blood samples were collected and changes in serum levels of cytokines interferon gamma (IFNg), Interleukin 10 (IL-10), Interleukin 12 (IL-12)p70, Interleukin 1b (IL-1b), Interleukin 2 (IL-2), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and tumor necrosis factor (TNF) were assessed by the multiplexed mesoscale assay. Significance of changes in serum levels of cytokines was determined by p value (Wilcoxon test) and the median and interquartile range of data.

Time frame:
Pre (Baseline) and Day 85 after 6 vaccinations
Reported as:
Median · pg/ml
Changes in Serum Levels of Cytokines
pg/ml4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Median IFNg Pre3.63 (2.47 to 6.12)3.56 (2.99 to 4.13)2.805 (1.97 to 3.6)4.47 (4.05 to 7.48)
Median IFNg d852.64 (2.17 to 3.17)2.83 (2.62 to 3.04)2.84 (1.76 to 4.71)4.9 (2.91 to 6.81)
Median IL-10 Pre0.24 (0.17 to 0.54)0.215 (0.2 to 0.23)0.21 (0.17 to 0.28)0.4 (0.31 to 0.47)
Median IL-10 d850.26 (0.23 to 0.39)0.285 (0.28 to 0.29)0.24 (0.18 to 0.31)0.4 (0.26 to 0.52)
Median IL-12p70 Pre0.2 (0.2 to 0.22)0.22 (0.2 to 0.24)0.2 (0.2 to 0.2)0.2 (0.2 to 0.37)
Median IL-12p70 d850.2 (0.2 to 0.28)0.2 (0.2 to 0.2)0.2 (0.2 to 0.2)0.2 (0.2 to 0.26)
Median IL-1b Pre0.24 (0.24 to 1.15)0.24 (0.24 to 0.24)0.24 (0.24 to 0.24)0.24 (0.24 to 2.52)
Median IL-1b d850.24 (0.24 to 0.25)0.24 (0.24 to 0.24)0.24 (0.24 to 0.24)0.24 (0.24 to 0.89)
Median IL-2 Pre0.64 (0.64 to 2.40)0.64 (0.64 to 0.64)0.64 (0.64 to 0.64)0.64 (0.64 to 0.80)
Median IL-2 d850.64 (0.64 to 0.93)0.64 (0.64 to 0.64)0.64 (0.64 to 0.64)0.64 (0.64 to 0.70)
Median IL-6 Pre0.88 (0.71 to 2.85)0.78 (0.66 to 0.9)1.02 (0.52 to 1.3)2.37 (0.69 to 15.3)
Median IL-6 d850.97 (0.74 to 1.23)0.855 (0.76 to 0.95)1.04 (0.54 to 1.97)2.84 (0.90 to 4.84)
Median IL-8 Pre56.45 (16.84 to 487.6)43.87 (16.05 to 71.69)37.49 (18 to 91.01)63.52 (33.7 to 560.2)
Median IL-8 d8533.29 (30.52 to 124.5)61.85 (44.98 to 78.71)43.27 (17.99 to 140.1)73.21 (38.62 to 200.9)
Median TNF Pre1.54 (1.19 to 8.19)1.315 (1.24 to 1.39)1.62 (1.25 to 2.26)3.59 (2.19 to 9.24)
Median TNF d851.63 (1.45 to 1.81)1.465 (1.23 to 1.7)1.67 (1.38 to 2.07)2.74 (2.26 to 3.77)
Statistical analysis
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.375 (The reported p-value is representative of the changes in levels of IFNg cytokines at dose level 1.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.4808 (The reported p-value is representative of the changes in levels of all IFNg cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.7334 (The reported p-value is representative of the changes in levels of IFNg cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon · p = 0.7109 (The reported p-value is representative of the changes in levels of IFNg cytokines at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.4347 (The reported p-value is representative of the changes in levels of all IL10 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon · p = >0.9999 (The reported p-value is representative of the changes in levels of IL10 cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.748 (The reported p-value is representative of the changes in levels of IL10 cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.8203The reported p-value is representative of the changes in levels of IL10 cytokines at dose level 4.
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.5625 (The reported p-value is representative of the changes in levels of all IL12p70 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of IL12p70 cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of IL12p70 cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.5 (The reported p-value is representative of the changes in levels of IL12p70 cytokines at dose level 14)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.6846 (The reported p-value is representative of the changes in levels of all IL1b cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of IL1b cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.5 (The reported p-value is representative of the changes in levels of IL1b cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of IL1b cytokines at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.4375 (The reported p-value is representative of the changes in levels of all IL-2 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of IL-2 cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of IL-2 cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.75 (The reported p-value is representative of the changes in levels of IL-2 cytokines at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.4525 (The reported p-value is representative of the changes in levels of all IL-6 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)The reported p-value is representative of the changes in levels of IL-6 cytokines at dose level 1.
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.875 (The reported p-value is representative of the changes in levels of IL-6 cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.4316
  • 80 YU (Dose Level 4) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of IL-6 cytokines at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.9906 (The reported p-value is representative of the changes in levels of all IL-8 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.625The reported p-value is representative of the changes in levels of IL-8 cytokines at dose level 1.
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.791 (The reported p-value is representative of the changes in levels of IL-8 cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.8203 (The reported p-value is representative of the changes in levels of IL-8 cytokines at dose level 4.)
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = >0.9999 (The reported p-value is representative of the changes in levels of all TNF cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.875 (The reported p-value is representative of the changes in levels of TNF cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.9658 (The reported p-value is representative of the changes in levels of TNF cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.6523 (The reported p-value is representative of the changes in levels of TNF cytokines at dose level 4.)
SecondaryChanges in Soluble Cluster of Differentiation 27 (sCD27)

Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27 was determined by p value (Wilcoxon test) and the median and interquartile range of data.

Time frame:
Pre (Baseline) and Day 85 after 6 vaccinations
Reported as:
Median · U/ml
Changes in Soluble Cluster of Differentiation 27 (sCD27)
U/ml4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Median sCD27 Pre99.07 (91.13 to 131)98.63 (87.12 to 110.1)97.47 (85.15 to 110.9)128.4 (123.9 to 145.6)
Median sCD27 d8597.17 (92.07 to 1112)92.07 (83.3 to 100.8)101.7 (98.85 to 105.1)133.1 (129.7 to 155.8)
Statistical analysis
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.2901 (The reported p-value is representative of the changes in levels of all sCD27 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.375 (The reported p-value is representative of the changes in levels of sCD27 cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.2036 (The reported p-value is representative of the changes in levels of sCD27 cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.0742 (The reported p-value is representative of the changes in levels of sCD27 cytokines at dose level 4.)
SecondaryMedian Ratio of Soluble Cluster of Differentiation 27:40L (sCD27:sCD40L)

Blood samples were collected and changes in serum levels of the ratio of soluble sCD27:sCD40L was assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27:sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.

Time frame:
Pre (Baseline) and Day 85 after 6 vaccinations
Reported as:
Median · Ratio
Median Ratio of Soluble Cluster of Differentiation 27:40L (sCD27:sCD40L)
Ratio4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Median sCD27:sCD40L Pre5.982 (5.71 to 11.67)9.57 (7.88 to 11.26)9.571 (7.67 to 19.89)8.57 (6.93 to 10.62)
Median sCD27:sCD40L d856.428 (4.79 to 9.43)8.294 (7.29 to 9.29)10.47 (6.63 to 19.38)8.257 (6.96 to 8.91)
Statistical analysis
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.1004 (The reported p-value is representative of the changes in levels of all ratio sCD27:sCD40AL cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.625 (The reported p-value is representative of the changes in levels of ratio sCD27:sCD40L cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.6772 (The reported p-value is representative of the changes in levels of ratio sCD27:sCD40L cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.3008 (The reported p-value is representative of the changes in levels of ratio sCD27:sCD40L cytokines at dose level 4.)
SecondaryChanges in Soluble Cluster of Differentiation 40L (sCD40L)

Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.

Time frame:
Pre (Baseline) and Day 85 after 6 vaccinations
Reported as:
Median · ng/ml
Changes in Soluble Cluster of Differentiation 40L (sCD40L)
ng/ml4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Median sCD40L Pre15.3 (11.39 to 17.99)10.24 (9.78 to 11.06)9.648 (5.27 to 13.99)14.72 (13.67 to 18.74)
Median sCD40L d8515.23 (11.96 to 19.42)11.14 (10.84 to 11.43)9.854 (5.86 to 14.52)18.57 (16.09 to 19.51)
Statistical analysis
  • 4 YU (Dose Level 1) vs 40 YU (Dose Level 3) vs 80 YU (Dose Level 4) · Wilcoxon test · p = 0.0621 (The reported p-value is representative of the changes in levels of all sCD40L cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n\>2 to do paired analyses.)
  • 4 YU (Dose Level 1) · Wilcoxon test · p = 0.875 (The reported p-value is representative of the changes in levels of sCD40L cytokines at dose level 1.)
  • 40 YU (Dose Level 3) · Wilcoxon test · p = 0.2402 (The reported p-value is representative of the changes in levels of sCD40L cytokines at dose level 3.)
  • 80 YU (Dose Level 4) · Wilcoxon test · p = 0.3008 (The reported p-value is representative of the changes in levels of sCD40L cytokines at dose level 4.)

Adverse events

Collected over 4 years and 25 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
4 YU (Dose Level 1)0/4 (0%)0/4 (0%)4/4 (100%)
16 YU (Dose Level 2)0/3 (0%)0/3 (0%)3/3 (100%)
40 YU (Dose Level 3)0/16 (0%)5/16 (31.3%)16/16 (100%)
80 YU (Dose Level 4)0/11 (0%)6/11 (54.5%)10/11 (90.9%)
Most frequent serious events
Showing 10 of 19
Most frequent serious events
Event4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Small intestinal obstructionGastrointestinal disorders0/40/33/162/11
Wound infectionInfections and infestations0/40/31/161/11
AtelectasisRespiratory, thoracic and mediastinal disorders0/40/30/161/11
Bone infectionInfections and infestations0/40/30/161/11
CholecystitisHepatobiliary disorders0/40/30/161/11
Eye infectionEye disorders0/40/30/161/11
FatigueGeneral disorders0/40/30/161/11
Lung infectionInfections and infestations0/40/30/161/11
Respiratory, thoracic and mediastinal disorders - Other, lung obstructionRespiratory, thoracic and mediastinal disorders0/40/30/161/11
Soft tissue infectionInfections and infestations0/40/30/161/11
Most frequent other events
Showing 10 of 125
Most frequent other events
Event4 YU (Dose Level 1)16 YU (Dose Level 2)40 YU (Dose Level 3)80 YU (Dose Level 4)
Injection site reactionGeneral disorders4/41/30/169/11
Injection site reactionSkin and subcutaneous tissue disorders4/40/310/160/11
Lymphocyte count decreasedInvestigations3/41/30/160/11
AnemiaBlood and lymphatic system disorders0/42/311/163/11
HypoalbuminemiaMetabolism and nutrition disorders2/40/30/160/11
PainGeneral disorders2/40/30/163/11
HyperglycemiaMetabolism and nutrition disorders0/41/30/165/11
FatigueGeneral disorders0/40/32/164/11
Flu like symptomsGeneral disorders1/41/30/161/11
Platelet count decreasedInvestigations1/41/30/160/11

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)All Participants
<=18 years0
Between 18 and 65 years24
>=65 years10
Age, Continuous
Age, Continuous(years)All Participants
Median58 (32 to 79)
Sex: Female, Male
Sex: Female, Male(Participants)All Participants
Female15
Male19
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Participants
American Indian or Alaska Native0
Asian3
Native Hawaiian or Other Pacific Islander0
Black or African American1
White30
More than one race0
Unknown or Not Reported0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)All Participants
Hispanic or Latino0
Not Hispanic or Latino33
Mexican, Puerto Rican, Cuban Central or So. Americ1
Region of Enrollment
Region of Enrollment(Participants)All Participants
United States34
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants)All Participants
014
120
Tumor Type
Tumor Type(Participants)All Participants
Colorectal11
Chordoma11
Breast5
Pancreatic3
Prostate2
Urothelial1
Lung1

4 further baseline measures are reported on the registry.

08

Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
09

References and documents

Publications

  • Baranova AV, Lobashev AV, Ivanov DV, Krukovskaya LL, Yankovsky NK, Kozlov AP. In silico screening for tumour-specific expressed sequences in human genome. FEBS Lett. 2001 Nov 9;508(1):143-8. doi: 10.1016/s0014-5793(01)03028-9. PubMed 11707285 ↗
  • Krukovskaja LL, Baranova A, Tyezelova T, Polev D, Kozlov AP. Experimental study of human expressed sequences newly identified in silico as tumor specific. Tumour Biol. 2005 Jan-Feb;26(1):17-24. doi: 10.1159/000084182. Epub 2005 Feb 28. PubMed 15741768 ↗
  • Palena C, Polev DE, Tsang KY, Fernando RI, Litzinger M, Krukovskaya LL, Baranova AV, Kozlov AP, Schlom J. The human T-box mesodermal transcription factor Brachyury is a candidate target for T-cell-mediated cancer immunotherapy. Clin Cancer Res. 2007 Apr 15;13(8):2471-8. doi: 10.1158/1078-0432.CCR-06-2353. PubMed 17438107 ↗
  • Heery CR, Singh BH, Rauckhorst M, Marte JL, Donahue RN, Grenga I, Rodell TC, Dahut W, Arlen PM, Madan RA, Schlom J, Gulley JL. Phase I Trial of a Yeast-Based Therapeutic Cancer Vaccine (GI-6301) Targeting the Transcription Factor Brachyury. Cancer Immunol Res. 2015 Nov;3(11):1248-56. doi: 10.1158/2326-6066.CIR-15-0119. Epub 2015 Jun 30. PubMed 26130065 ↗
  • Fenerty KE, Patronas NJ, Heery CR, Gulley JL, Folio LR. Resources Required for Semi-Automatic Volumetric Measurements in Metastatic Chordoma: Is Potentially Improved Tumor Burden Assessment Worth the Time Burden? J Digit Imaging. 2016 Jun;29(3):357-64. doi: 10.1007/s10278-015-9846-9. PubMed 26596767 ↗

Study documents

  • Protocol, analysis plan and consent form · Jan 6, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 29, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01519817
Lead sponsor
National Cancer Institute (NCI)
Responsible party
James Gulley, M.D. (Senior Investigator, National Cancer Institute (NCI)) — Principal investigator
First posted
Jan 27, 2012
Start date
Jan 5, 2012
Primary completion
Mar 3, 2016
Completion
Sep 1, 2016
Results posted
Jul 31, 2017
Last update
Jan 29, 2018

Study contacts

James L Gulley, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

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