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Immunotherapy Study for Patients With Stage IV Melanoma

Sponsor
NewLink Genetics Corporation (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02054520
Collaborator
(none)
47
Enrollment
5
Locations
6
Arms
227
Duration (Months)
9.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effectiveness of immune checkpoint inhibitors (drugs called ipilimumab, nivolumab, or pembrolizumab), either given alone, or in combination with the experimental immunotherapy drug, dorgenmeltucel-L, for melanoma. We hypothesize that this form of combinatorial immunotherapy will result in tumor stabilization or shrinkage, significant prolongation of progression-free, disease-free or overall survival compared to the use of immune checkpoint inhibitors alone.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

According to statistics of the American Cancer Society, an estimated 73,800 individuals will be diagnosed with melanoma and 9,900 will die of the disease in 2015 in the Unites States despite current therapy. This protocol attempts to exploit an approach to melanoma immunotherapy using a naturally occurring barrier to xenotransplantation in humans to increase the effectiveness of immunizing patients against their melanoma. The expression of the murine (1,3)galactosyltransferase [alpha(1,3)GT] gene results in the cell surface expression of (1,3)galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation.

These antibodies may comprise up to 1% of serum IgG. In this phase 2b study, patients with advanced stage melanoma will receive immune checkpoint inhibition consisting of ipilimumab, nivolumab, or pembrolizumab per the treating physician's standard of care. In addition to the immune checkpoint therapy, half of the patients will also receive dorgenmeltucel-L. Dorgenmeltucel-L is composed of irradiated allogeneic melanoma cell lines (HAM-1, HAM-2 and HAM-3). These cell lines have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine (1,3)GT gene. Endpoints of the study include safety assessments, efficacy, and immunological responses.

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2b Study of Immune Checkpoint Inhibition With or Without Dorgenmeltucel-L (HyperAcute Melanoma) Immunotherapy for Stage IV Melanoma Patients
Study Start Date :
Jun 1, 2014
Actual Primary Completion Date :
Apr 5, 2018
Anticipated Study Completion Date :
May 1, 2033

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab

Arm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year.

Drug: HyperAcute®-Melanoma (HAM) Immunotherapy
Other Names:
  • HyperAcute®-Melanoma
  • HAM
  • Dorgenmeltucel-L

    • Drug: Ipilimumab
    Other Names:
  • YERVOY
  • MDX-010
  • MDX-101

    		•
    Active Comparator: Arm 2A Ipilimumab Alone

    Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses.

    Drug: Ipilimumab
    Other Names:
  • YERVOY
  • MDX-010
  • MDX-101

    		•
    Experimental: Arm 1B HyperAcute®-Melanoma (HAM) + nivolumab

    Arm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year.

    Drug: HyperAcute®-Melanoma (HAM) Immunotherapy
    Other Names:
  • HyperAcute®-Melanoma
  • HAM
  • Dorgenmeltucel-L

    • Drug: Nivolumab
    Other Names:
  • Opdivo

    		•
    Active Comparator: Arm 2B Nivolumab alone

    Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks

    Drug: Nivolumab
    Other Names:
  • Opdivo

    		•
    Experimental: Arm 1C HyperAcute®-Melanoma (HAM) + pembrolizumab

    Arm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year.

    Drug: HyperAcute®-Melanoma (HAM) Immunotherapy
    Other Names:
  • HyperAcute®-Melanoma
  • HAM
  • Dorgenmeltucel-L

    • Drug: Pembrolizumab
    Other Names:
  • Keytruda

    		•
    Active Comparator: Arm 2C Pembrolizumab alone

    Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks

    Drug: Pembrolizumab
    Other Names:
  • Keytruda

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety and Tolerability Assessed by Development of AEs and Laboratory Parameters [2 years]

      To determine the safety of administration of immune checkpoint inhibition consisting of ipilimumab, nivolumab, or pembrolizumab with or without dorgenmeltucel-L immunotherapy for patients with stage IV melanoma

    2. Clinical Response Rate [2 years]

      To estimate the clinical response rate of metastatic melanoma patients after immunotherapy with dorgenmeltucel-L immunotherapy plus immune checkpoint inhibition

    Secondary Outcome Measures

    1. Clinical Activity [2 years]

      To estimate the disease-free survival (DFS), progression-free survival (PFS), overall survival (OS) and duration of overall response, duration of complete response (CR) and duration of stable disease (SD) of patients with stage IV melanoma treated with immune checkpoint inhibition with or without dorgenmeltucel-L immunotherapy.

    2. Anti-tumor Immune Response [2 years]

      To measure anti-tumor immune responses in melanoma metastases in responding and non-responding patients.

    3. Immune Activation [2 years]

      To further determine whether the humoral and cellular mediated arms of the host immune system are activated secondary to dorgenmeltucel-L immunotherapy combined with immune checkpoint inhibition.

    4. Anti-Tumor Mechanism [2 years]

      To perform correlative studies of patient samples (blood and tumor when available) to determine the mechanism of any observed anti-tumor effect.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histological/cytological diagnosis of melanoma. AJCC stage IV (any T, any N, M1), metastatic, progressive, refractory, melanoma.

    • Patients may have advanced unresectable stage IV disease, resectable stave IV disease or recently resected stage IV disease (<10 weeks prior) with no apparent disease.

    • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.

    • Serum albumin ≥3.0 gm/dL.

    • Adequate organ function including:

      1. Marrow: Hemoglobin ≥10.0 gm/dL, absolute granulocyte count (AGC) ≥1,000/mm3, platelets ≥75,000/mm3, absolute lymphocyte count ≥475/mm3.
      1. Hepatic: Serum total bilirubin ≤2.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤2.5 x ULN.
      1. Renal: Serum creatinine (sCr) ≤ 1.5 x upper limit of normal.

    • Prior therapy for melanoma that may include surgery, radiation therapy, immunotherapy including interleukins and interferon, and/or ≤2 different regiments of systemic chemotherapy, targeted therapy, or other experimental systemic therapies. Prior treatment with immune checkpoint inhibitors is not allowed.

    • Patients must be ≥4 weeks since major surgery, radiotherapy, chemotherapy (6 weeks if they were treated with nitrosureas) or biotherapy/targeted therapies.

    • Patients must have the ability to understand the study, its risks, side effects, potential benefits and be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney (DPA).

    • Male and female subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental drug, and for one month after the last immunization.

    Exclusion Criteria:

    • Age <18-years-old.

    • Active CNS metastases or carcinomatous meningitis. Patients with CNS lesions that have been treated and who have no evidence of progression in the brain on CT/MRI for

    ≥1 month are eligible. Pregnant or nursing women due to the unknown effects of immunization on the developing fetus or newborn infant.

    • Other malignancy within five years, except the following may be eligible:

    • patients curatively treated for localized squamous or basal cell carcinoma of the skin or for carcinoma in situ of the uterine cervix (CIN) or breast,

    • patients with a history of malignant tumor who have been disease free for at least five years and are not currently being treated.

    • History of an allogeneic solid organ transplant or bone marrow transplant, or current active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.

    • Subjects taking systemic (parentally or orally) corticosteroid therapy for any reason, including replacement therapy for hypoadrenalism, are not eligible. Topical steroids are acceptable as are intranasal steroids.

    • Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C), if deemed clinically significant by the treating physician.

    • Evidence of active autoimmune disease (e.g., systemic lupus erythematosis, rheumatoid arthritis, with the exception of vitiligo. Patients with a remote history of asthma or mild asthma are eligible.

    • Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis).

    • Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc).

    • Patients having previously undergone splenectomy.

    • Patients with known hepatitis or unstable liver disease, and/or positive serologies for Hepatitis B or C and HIV.

    • Patients with sickle-cell anemia or thalassemia major.

    • Subjects who received prior treatment with immune checkpoint inhibition, consisting of ipilimumab, tremelimumab, nivolumab, pembrolizumab or other antibody to CTLA4 or PD-1.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Oncology Specialists Niles Illinois United States 60714
    2 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    3 University of Kansas Cancer Center Westwood Kansas United States
    4 Wake Forest Baptist Health Winston-Salem North Carolina United States 27157
    5 University of Tennessee Medical Center Knoxville Tennessee United States 37920

    Sponsors and Collaborators

    • NewLink Genetics Corporation

    Investigators

    • Study Director: Eugene Kennedy, MD, NewLink Genetics Corporation

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    NewLink Genetics Corporation
    ClinicalTrials.gov Identifier:
    NCT02054520
    Other Study ID Numbers:
    • NLG0304
    • 1303-1217
    First Posted:
    Feb 4, 2014
    Last Update Posted:
    May 28, 2020
    Last Verified:
    May 1, 2020
    Keywords provided by NewLink Genetics Corporation
    Stage IV
    metastatic melanoma
    Additional relevant MeSH terms:
    Melanoma
    Pembrolizumab
    Nivolumab
    Ipilimumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail The enrollment and treatment phase of this trial was terminated early, but the FDA required 15 year long term follow-up for gene therapy is still ongoing.
    Arm/Group Title Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone
    Arm/Group Description Arm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Ipilimumab Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses. Ipilimumab Arm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Nivolumab Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks Nivolumab Arm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Pembrolizumab Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks Pembrolizumab
    Period Title: Overall Study
    STARTED 11 16 6 6 5 3
    COMPLETED 2 11 0 0 0 0
    NOT COMPLETED 9 5 6 6 5 3

    Baseline Characteristics

    Arm/Group Title Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone Total
    Arm/Group Description Arm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Ipilimumab Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses. Ipilimumab Arm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Nivolumab Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks Nivolumab Arm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Pembrolizumab Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks Pembrolizumab Total of all reporting groups
    Overall Participants 11 16 6 6 5 3 47
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    59.5
    63.4
    61.3
    67.5
    60.8
    62.3
    62.4
    Sex: Female, Male (Count of Participants)
    Female
    4
    36.4%
    4
    25%
    3
    50%
    2
    33.3%
    3
    60%
    1
    33.3%
    17
    36.2%
    Male
    7
    63.6%
    12
    75%
    3
    50%
    4
    66.7%
    2
    40%
    2
    66.7%
    30
    63.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    11
    100%
    16
    100%
    6
    100%
    6
    100%
    5
    100%
    3
    100%
    47
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    11
    100%
    16
    100%
    6
    100%
    6
    100%
    5
    100%
    3
    100%
    47
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    ECOG Performance Status (Count of Participants)
    ECOG PS Score 0
    10
    90.9%
    10
    62.5%
    4
    66.7%
    3
    50%
    4
    80%
    2
    66.7%
    33
    70.2%
    ECOG PS Score 1
    1
    9.1%
    6
    37.5%
    2
    33.3%
    3
    50%
    1
    20%
    1
    33.3%
    14
    29.8%

    Outcome Measures

    1. Primary Outcome
    Title Safety and Tolerability Assessed by Development of AEs and Laboratory Parameters
    Description To determine the safety of administration of immune checkpoint inhibition consisting of ipilimumab, nivolumab, or pembrolizumab with or without dorgenmeltucel-L immunotherapy for patients with stage IV melanoma
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    The primary population for safety analyses is the safety analysis set, defined as all randomized subjects who receive at least one administration of study treatment (dorgenmeltucel-L or immune checkpoint therapy).
    Arm/Group Title Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone
    Arm/Group Description Arm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Ipilimumab Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses. Ipilimumab Arm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Nivolumab Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks Nivolumab Arm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Pembrolizumab Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks Pembrolizumab
    Measure Participants 11 16 6 6 5 3
    At least one TEAE
    11
    100%
    16
    100%
    6
    100%
    5
    83.3%
    5
    100%
    3
    100%
    At least one Serious TEAE
    3
    27.3%
    3
    18.8%
    1
    16.7%
    2
    33.3%
    0
    0%
    2
    66.7%
    At least one DLT
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    At least one severe TEAE
    7
    63.6%
    6
    37.5%
    4
    66.7%
    2
    33.3%
    1
    20%
    1
    33.3%
    At least one related TEAE
    11
    100%
    0
    0%
    6
    100%
    0
    0%
    5
    100%
    0
    0%
    At least one TEAE leading to discontinuation
    1
    9.1%
    4
    25%
    2
    33.3%
    1
    16.7%
    1
    20%
    0
    0%
    2. Primary Outcome
    Title Clinical Response Rate
    Description To estimate the clinical response rate of metastatic melanoma patients after immunotherapy with dorgenmeltucel-L immunotherapy plus immune checkpoint inhibition
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    The enrollment and treatment phase of this trial was terminated early, but the FDA required 15 year long term follow-up for gene therapy is still ongoing. The analysis of clinical response rate was limited as enrollment to the trial was closed early.
    Arm/Group Title Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone
    Arm/Group Description Arm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Ipilimumab Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses. Ipilimumab Arm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Nivolumab Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks Nivolumab Arm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Pembrolizumab Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks Pembrolizumab
    Measure Participants 8 14 4 2 4 3
    Count of Participants [Participants]
    2
    18.2%
    4
    25%
    1
    16.7%
    0
    0%
    2
    40%
    1
    33.3%
    3. Secondary Outcome
    Title Clinical Activity
    Description To estimate the disease-free survival (DFS), progression-free survival (PFS), overall survival (OS) and duration of overall response, duration of complete response (CR) and duration of stable disease (SD) of patients with stage IV melanoma treated with immune checkpoint inhibition with or without dorgenmeltucel-L immunotherapy.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    Title Anti-tumor Immune Response
    Description To measure anti-tumor immune responses in melanoma metastases in responding and non-responding patients.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    Title Immune Activation
    Description To further determine whether the humoral and cellular mediated arms of the host immune system are activated secondary to dorgenmeltucel-L immunotherapy combined with immune checkpoint inhibition.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    Title Anti-Tumor Mechanism
    Description To perform correlative studies of patient samples (blood and tumor when available) to determine the mechanism of any observed anti-tumor effect.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame All AEs were collected occurring during the study period from the time of the first dose to the last day of the 30-day post-treatment follow-up period.
    Adverse Event Reporting Description
    Arm/Group Title Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone
    Arm/Group Description Arm 1A will receive ipilimumab at 3 mg/kg given every 3 weeks for 4 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Ipilimumab Arm 2A will receive ipilimumab alone at 3 mg/kg every 3 weeks for a total of four doses. Ipilimumab Arm 1B will receive nivolumab alone at 3 mg/kg given every 2 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Nivolumab Arm 2B will receive nivolumab alone at 3 mg/kg given every 2 weeks Nivolumab Arm 1C will receive pembrolizumab at 2 mg/kg given every 3 weeks and 300 Million HyperAcute®-Melanoma (HAM) Immunotherapy cells per each immunization, given every week for 4 weeks, every 2 weeks for 5 months, every month for 6 months, and every 3 months for one year. HyperAcute®-Melanoma (HAM) Immunotherapy Pembrolizumab Arm 2C will receive pembrolizumab at 2 mg/kg given every 3 weeks Pembrolizumab
    All Cause Mortality
    Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/11 (45.5%) 7/16 (43.8%) 2/6 (33.3%) 1/6 (16.7%) 1/5 (20%) 2/3 (66.7%)
    Serious Adverse Events
    Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/11 (27.3%) 3/16 (18.8%) 1/6 (16.7%) 2/6 (33.3%) 0/5 (0%) 2/3 (66.7%)
    Gastrointestinal disorders
    Diarrhea 1/11 (9.1%) 1 1/16 (6.3%) 1 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 0/3 (0%) 0
    Melena 0/11 (0%) 0 1/16 (6.3%) 1 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 0/3 (0%) 0
    Nausea 1/11 (9.1%) 1 0/16 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 0/3 (0%) 0
    Vomiting 0/11 (0%) 0 0/16 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/5 (0%) 0 0/3 (0%) 0
    Hepatobiliary disorders
    Gallbladder pain 0/11 (0%) 0 0/16 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1
    Immune system disorders
    Hypersensitivity 1/11 (9.1%) 1 0/16 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 0/3 (0%) 0
    Infections and infestations
    Diverticulitis 0/11 (0%) 0 1/16 (6.3%) 1 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 0/3 (0%) 0
    Sepsis 0/11 (0%) 0 0/16 (0%) 0 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 2
    Metabolism and nutrition disorders
    Diabetic Ketoacidosis 0/11 (0%) 0 0/16 (0%) 0 1/6 (16.7%) 1 0/6 (0%) 0 0/5 (0%) 0 0/3 (0%) 0
    Dehydration 0/11 (0%) 0 1/16 (6.3%) 1 0/6 (0%) 0 0/6 (0%) 0 0/5 (0%) 0 0/3 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure 0/11 (0%) 0 0/16 (0%) 0 0/6 (0%) 0 1/6 (16.7%) 1 0/5 (0%) 0 0/3 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm 1A HyperAcute®-Melanoma (HAM) + Ipilimumab Arm 2A Ipilimumab Alone Arm 1B HyperAcute®-Melanoma (HAM) + Nivolumab Arm 2B Nivolumab Alone Arm 1C HyperAcute®-Melanoma (HAM) + Pembrolizumab Arm 2C Pembrolizumab Alone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/11 (100%) 16/16 (100%) 6/6 (100%) 5/6 (83.3%) 5/5 (100%) 3/3 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 2/5 (40%) 0/3 (0%)
    Leukocytosis 0/11 (0%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Lymph node pain 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Lymphadenopathy 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Thrombocytopenia 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Thrombocytosis 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Cardiac disorders
    Angina Pectoris 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Atrial Fibrillation 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Bradycardia 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Myocardial infarction 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Myocarditis 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Palpitations 2/11 (18.2%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Supraventricular Tachycardia 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Tachycardia 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Ear and labyrinth disorders
    Ear Haemorrhage 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Ear Pain 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Middle Ear Inflammation 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Vertigo 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Endocrine disorders
    Hypophysitis 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hypopituitarism 1/11 (9.1%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hypothyroidism 0/11 (0%) 2/16 (12.5%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Eye disorders
    Diplopia 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Eye Discharge 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Watering Eyes 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Gastrointestinal disorders
    Abdominal distention 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Abdominal Pain 0/11 (0%) 2/16 (12.5%) 2/6 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Abdominal tenderness 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Constipation 3/11 (27.3%) 4/16 (25%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Diarrhoea 5/11 (45.5%) 4/16 (25%) 3/6 (50%) 2/6 (33.3%) 1/5 (20%) 0/3 (0%)
    Dry mouth 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Dyspepsia 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Dysphagia 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    enterocolitis 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Flatulence 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Gastoesophaeal Reflux Disease 0/11 (0%) 0/16 (0%) 2/6 (33.3%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Gingival Pain 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Haematochezia 0/11 (0%) 2/16 (12.5%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Lip pain 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Melaena 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Nausea 9/11 (81.8%) 3/16 (18.8%) 4/6 (66.7%) 4/6 (66.7%) 2/5 (40%) 0/3 (0%)
    Oral Pain 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Stomach Pain 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Stomatitis 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Vomiting 3/11 (27.3%) 1/16 (6.3%) 5/6 (83.3%) 3/6 (50%) 1/5 (20%) 0/3 (0%)
    General disorders
    Asthenia 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Chest pain 2/11 (18.2%) 0/16 (0%) 2/6 (33.3%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Chills 5/11 (45.5%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Fatigue 9/11 (81.8%) 7/16 (43.8%) 5/6 (83.3%) 3/6 (50%) 5/5 (100%) 2/3 (66.7%)
    Inflammation 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Influenza like illness 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Injection site erythema 11/11 (100%) 0/16 (0%) 6/6 (100%) 0/6 (0%) 4/5 (80%) 0/3 (0%)
    Injection site induration 9/11 (81.8%) 0/16 (0%) 4/6 (66.7%) 0/6 (0%) 5/5 (100%) 0/3 (0%)
    Injection site irritation 4/11 (36.4%) 0/16 (0%) 2/6 (33.3%) 0/6 (0%) 4/5 (80%) 0/3 (0%)
    Injection site pain 9/11 (81.8%) 0/16 (0%) 5/6 (83.3%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Injection site Pruritus 8/11 (72.7%) 0/16 (0%) 6/6 (100%) 0/6 (0%) 2/5 (40%) 0/3 (0%)
    Injection Site Reaction 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Injection site swelling 11/11 (100%) 0/16 (0%) 5/6 (83.3%) 0/6 (0%) 4/5 (80%) 0/3 (0%)
    Injection site warmth 6/11 (54.5%) 0/16 (0%) 4/6 (66.7%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Malaise 3/11 (27.3%) 0/16 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 1/3 (33.3%)
    Mucosal Inflammation 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Non-cardiac chest pain 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Oedema 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Oedema peripheral 1/11 (9.1%) 1/16 (6.3%) 2/6 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Pain 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Peripheral Swelling 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Pyrexia 4/11 (36.4%) 3/16 (18.8%) 2/6 (33.3%) 2/6 (33.3%) 1/5 (20%) 0/3 (0%)
    Hepatobiliary disorders
    Gallbladder pain 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/3 (33.3%)
    Hyperbilirubinaemia 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 1/3 (33.3%)
    Immune system disorders
    Autoimmune disorder 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Hypersensitivity 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Infections and infestations
    Bronchitis 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Cellulitis 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 1/3 (33.3%)
    Conjunctivitis 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Diverticulitis 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Ear Infection 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Escherichia bacteraemia 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Rhinitis 1/11 (9.1%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Sepsis 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/3 (33.3%)
    Sinusitis 0/11 (0%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Upper respiratory tract infection 2/11 (18.2%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Urinary Tract Infection 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Injury, poisoning and procedural complications
    Contusion 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Fall 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Incision Site Pain 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Skin injury 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Investigations
    Alanine Aminotransferase Increased 0/11 (0%) 2/16 (12.5%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 1/3 (33.3%)
    Aspartate Aminostransferase Increased 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 2/6 (33.3%) 1/5 (20%) 1/3 (33.3%)
    Blood alkaline phosphatase increased 0/11 (0%) 3/16 (18.8%) 1/6 (16.7%) 1/6 (16.7%) 1/5 (20%) 0/3 (0%)
    Blood creatine phosphokinase increased 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Blood Creatinine Increased 0/11 (0%) 0/16 (0%) 4/6 (66.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Blood immunoglobulin E increased 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Blood immunoglobulin G increased 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Blood thyroid stimulating hormone decreased 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Blood thyroid stimulating hormone increased 0/11 (0%) 2/16 (12.5%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Cortisol increased 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    C-reactive protein Increased 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Lymphocyte count decreased 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Thyroxine increased 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Weight Decreased 1/11 (9.1%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Weight Increased 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 5/11 (45.5%) 2/16 (12.5%) 3/6 (50%) 1/6 (16.7%) 1/5 (20%) 0/3 (0%)
    Dehydration 3/11 (27.3%) 1/16 (6.3%) 2/6 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Diabetes mellitus 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Diabetic Ketoacidosis 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hypercalcaemia 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hyperglycaemia 1/11 (9.1%) 1/16 (6.3%) 3/6 (50%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hyperkalaemia 2/11 (18.2%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hypoalbuminaemia 1/11 (9.1%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Hypokalaemia 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 1/6 (16.7%) 1/5 (20%) 0/3 (0%)
    Hyponatraemia 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/11 (0%) 3/16 (18.8%) 2/6 (33.3%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Arthritis 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Back pain 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    bone pain 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Flank Pain 0/11 (0%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Muscle Spasms 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Muscular weakness 1/11 (9.1%) 2/16 (12.5%) 0/6 (0%) 2/6 (33.3%) 0/5 (0%) 0/3 (0%)
    Musculoskeletal Pain 0/11 (0%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Myalgia 2/11 (18.2%) 0/16 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Myositis 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Neck Mass 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Neck Pain 0/11 (0%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Pain in extremity 2/11 (18.2%) 1/16 (6.3%) 3/6 (50%) 0/6 (0%) 0/5 (0%) 1/3 (33.3%)
    Tendonitis 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour Pain 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 1/3 (33.3%)
    Nervous system disorders
    Cognitive Disorder 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    disturbance in attention 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Dizziness 5/11 (45.5%) 4/16 (25%) 3/6 (50%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Dysaesthesia 0/11 (0%) 0/16 (0%) 2/6 (33.3%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Dysgeusia 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Encephalopathy 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Headache 4/11 (36.4%) 4/16 (25%) 5/6 (83.3%) 2/6 (33.3%) 2/5 (40%) 0/3 (0%)
    Hypoaesthesia 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    IIIrd nerve disorder 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Memory Impairment 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Migraine 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Peripheral Sensory Neuropathy 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Presyncope 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/3 (33.3%)
    Somnolence 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Tinnitus 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Tremor 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Psychiatric disorders
    agitation 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Anxiety 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Depression 1/11 (9.1%) 1/16 (6.3%) 2/6 (33.3%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Insomnia 3/11 (27.3%) 4/16 (25%) 1/6 (16.7%) 1/6 (16.7%) 1/5 (20%) 0/3 (0%)
    Libido decreased 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Renal and urinary disorders
    Acute Kidney Injury 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Chromaturia 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Haematuria 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Nocturia 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Polyuria 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Reproductive system and breast disorders
    Breast Discharge 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Vulvovaginal pruritus 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal Pain 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Atelectasis 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Cough 3/11 (27.3%) 2/16 (12.5%) 1/6 (16.7%) 2/6 (33.3%) 2/5 (40%) 0/3 (0%)
    Dysphonia 0/11 (0%) 0/16 (0%) 2/6 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Dyspnoea 1/11 (9.1%) 0/16 (0%) 2/6 (33.3%) 2/6 (33.3%) 2/5 (40%) 0/3 (0%)
    dyspnoea exertional 1/11 (9.1%) 0/16 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Nasal Congestion 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    oropharyngeal pain 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Orthopnoea 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    paranasal sinus discomfort 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Pleural Effusion 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Pneumothorax 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Respiratory Failure 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Rhinitis Allergic 1/11 (9.1%) 1/16 (6.3%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Tachypnoea 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Upper-airway cough syndrome 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Wheezing 1/11 (9.1%) 0/16 (0%) 2/6 (33.3%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis 1/11 (9.1%) 1/16 (6.3%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Eczema 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Erythema 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hair texture abnormal 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hyperhidrosis 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Hyperkeratosis 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Maculopapular Rash 1/11 (9.1%) 2/16 (12.5%) 2/6 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Night Sweats 0/11 (0%) 1/16 (6.3%) 2/6 (33.3%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Pain of skin 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Petechiae 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Pruritus 3/11 (27.3%) 10/16 (62.5%) 4/6 (66.7%) 2/6 (33.3%) 0/5 (0%) 0/3 (0%)
    Rash 2/11 (18.2%) 4/16 (25%) 2/6 (33.3%) 1/6 (16.7%) 1/5 (20%) 0/3 (0%)
    Rash Erythematous 1/11 (9.1%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Rash pruritic 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Skin Mass 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Vitiligo 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 1/5 (20%) 0/3 (0%)
    Yellow Skin 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Vascular disorders
    deep Vein Thrombosis 0/11 (0%) 0/16 (0%) 1/6 (16.7%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Embolism 0/11 (0%) 0/16 (0%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Hot flush 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Hypertension 0/11 (0%) 2/16 (12.5%) 1/6 (16.7%) 1/6 (16.7%) 0/5 (0%) 0/3 (0%)
    Hypotension 1/11 (9.1%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Orthostatic Hypotension 0/11 (0%) 1/16 (6.3%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 0/3 (0%)
    Superior vena cava syndrome 0/11 (0%) 0/16 (0%) 0/6 (0%) 0/6 (0%) 0/5 (0%) 1/3 (33.3%)

    Limitations/Caveats

    Early termination leading to small numbers of subjects analyzed. The enrollment and treatment phase of this trial was terminated early, but the FDA required 15 year long term follow-up for gene therapy is still ongoing.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Manager, Clinical Operations
    Organization NewLink Genetics Corporation
    Phone 515-598-5020 ext 2624
    Email csmith@linkp.com
    Responsible Party:
    NewLink Genetics Corporation
    ClinicalTrials.gov Identifier:
    NCT02054520
    Other Study ID Numbers:
    • NLG0304
    • 1303-1217
    First Posted:
    Feb 4, 2014
    Last Update Posted:
    May 28, 2020
    Last Verified:
    May 1, 2020