Clinical Trials /

Phase 1 Study of GRN-1201 in HLA-A*02 Subjects With Resected Melanoma

NCT02696356

Description:

This is a study of an investigational cancer vaccine called GRN-1201. Treatment with the GRN-1201 vaccine is a type of immunotherapy. The goal of immunotherapy is to stimulate the body's immune system (white blood cells) to attack cancer cells and kill them. GRN-1201 consists of 4 different peptides (small parts of proteins) that are expressed by melanoma cells. The intent of treatment with GRN-1201 is to increase your body's immune response to melanoma. To further increase your body's immune response against tumor cells, the GRN-1201 vaccine will be mixed with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF, also known as sargramostim). GM-CSF is a man-made protein that helps stimulate the immune system and increase the response against the tumor cells. This is a phase I study which means that this will be the first time GRN-1201 is given in combination with GM-CSF to humans. It will be tested in a small number of people to evaluate its safety, find a safe dose, and identify side effects. The safety of GRN-1201 will be tested at three different doses; the GM-CSF dose will remain the same.

Related Conditions:
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Phase 1 Study of GRN-1201 in HLA-A*02 Subjects With Resected <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: Phase 1 Study of GRN-1201 in HLA-A*02 Subjects With Resected Melanoma
  • Official Title: A Phase 1, Open-Label, Multi-Center, Multi-Dose Study of Intradermal GRN-1201 in HLA-A*02 Subjects With Resected Stage IIb, IIc or III Melanoma
  • Clinical Trial IDs

    NCT ID: NCT02696356

    ORG ID: GRN1201-001

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a study of an investigational cancer vaccine called GRN-1201. Treatment with the
    GRN-1201 vaccine is a type of immunotherapy. The goal of immunotherapy is to stimulate the
    body's immune system (white blood cells) to attack cancer cells and kill them. GRN-1201
    consists of 4 different peptides (small parts of proteins) that are expressed by melanoma
    cells. The intent of treatment with GRN-1201 is to increase your body's immune response to
    melanoma.

    To further increase your body's immune response against tumor cells, the GRN-1201 vaccine
    will be mixed with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF, also known as
    sargramostim). GM-CSF is a man-made protein that helps stimulate the immune system and
    increase the response against the tumor cells. This is a phase I study which means that this
    will be the first time GRN-1201 is given in combination with GM-CSF to humans. It will be
    tested in a small number of people to evaluate its safety, find a safe dose, and identify
    side effects. The safety of GRN-1201 will be tested at three different doses; the GM-CSF
    dose will remain the same.

    Detailed Description

    GRN-1201 is a novel HLA-A*02-restricted multiple-peptide, therapeutic cancer vaccine, being
    developed by GreenPeptide for the treatment of melanoma because it can induce immune
    responses against tumor associated antigens (TAAs), particularly cytotoxic T cell (CTL)
    responses. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF) (Leukine,
    SanofiAventis) will be administered in combination with GRN-1201 as an immuno-adjuvant

    In contrast to advanced melanoma, treatment options in the adjuvant setting are limited.
    Surgical resection is the primary treatment of Stage IIb, IIc, and III melanoma patients.
    The rate of disease recurrence in patients with American Joint Committee on Cancer (AJCC)
    TNM Stage II (T2-4N0M0) and Stage III (TanyN+M0) disease ranges between 20 -60%, with 5-year
    overall survival between 45 - 70%. Thus, safe and effective treatment options to reduce the
    risk of recurrence are much needed. Considering their generally safe nature, peptide-based
    cancer vaccines would be ideal to address this unmet medical need. Patients with Stage IIb,
    IIc or III melanoma are, in general, healthy following local therapy. They are anticipated
    to maintain an immune system uncompromised by chemotherapy or disease burden. Further, they
    may have already developed immune response to TAAs targeted by GRN-1201, which may increase
    the probability of developing effective immune responses. It is conceivable that the
    combination of peptide vaccines with an immune checkpoint inhibitor, especially with a PD-1
    pathway inhibitor, could enhance the efficacy of immunotherapy without increasing toxicity.
    Studies evaluating the combination of a melanoma vaccine with nivolumab in advanced melanoma
    [14] and resected high-risk metastatic melanoma patients [15] reported encouraging clinical
    outcome.

    The pre-clinical data suggest that GRN-1201 may have anti-tumor activity in the adjuvant
    setting or may enhance activity of other drugs such as checkpoint inhibitors in the adjuvant
    or metastatic disease setting, by enhancing immune responses against TAAs.

    Trial Arms

    Name Type Description Interventions
    Cohort 1 Experimental 0.1mg GRN-1201
    Cohort 2 Active Comparator 1.0mg GRN-1201
    Cohort 3 Experimental 3.0mg GRN-1201

    Eligibility Criteria

    Inclusion Criteria:

    - Males and females 18 years of age (at the time consent is obtained);

    - Provide written informed consent for study participation, approved by the appropriate
    institutional review board (IRB), and be willing and able to cooperate with all
    aspects of the protocol;

    - Resected, histologically proven, cutaneous melanoma determined to be Stage IIb, IIc,
    or III; according to the American Joint Commission of Cancer Staging, 7th edition

    - Human leukocyte antigen (HLA)-A*02+ by serology by an ASHI accredited laboratory;

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0;

    - Female subjects must have a negative serum human chorionic gonadotropic (hCG) test
    (pregnancy test not required for subjects with bilateral oophorectomy and/or
    hysterectomy or for those subjects who are >1 year post-menopausal); and

    - All female and male subjects of reproductive potential must agree to use an effective
    method of contraception, as determined by the Investigator, during and for 3 months
    after the last dose of study drug.

    Exclusion Criteria:

    - Inadequate hematologic or biologic function as determined by the following laboratory
    tests:

    - Hemoglobin <10 g/dL,

    - Platelet count <100,000/L,

    - Leukocyte count <3000/L,

    - Lymphocyte count <1000/L,

    - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >2 upper limit of
    normal (ULN),

    - Total bilirubin >ULN: Subjects with Gilbert's syndrome are allowed if total bilirubin
    is <3.0 mg/dL and direct bilirubin is ULN,

    - Serum creatinine >ULN, or Prothrombin time (PT) or international normalized ratio
    (INR) >1.5 ULN or activated partial thromboplastin time (aPTT) > 1.5 ULN

    - Greater than 3 months since melanoma resection;

    - Have known fungal, bacterial, and/or viral infection, including human
    immunodeficiency virus (HIV) or hepatitis virus (B or C);

    - Active immunosuppressive therapy associated with: Organ or allogeneic hematopoietic
    stem cell transplant, High-dose steroids, such as daily steroid doses in excess of 20
    mg/day of prednisone (Note: Use of intra-articular or topical corticosteroids or eye
    drops containing corticosteroids is acceptable.), or Inhaled corticosteroids;

    - Known history of autoimmune conditions including, but not limited to: rheumatoid
    arthritis, multiple sclerosis, lupus erythematosus, scleroderma, sarcoidosis,
    inflammatory bowel disease, idiopathic thrombocytopenia purpura, Graves' disease, or
    Hashimoto's thyroiditis;

    - Current requirement for anti-coagulation therapy that prolongs PT or aPTT 7. History
    of prior malignancy except: Curatively treated non-melanoma skin cancer; Solid tumor
    treated curatively >5 years previously without evidence of recurrence; or History of
    other malignancy that in the Investigator's opinion would not affect the
    determination of study treatment effect (e.g., superficial bladder cancer, or
    carcinoma in situ of the prostate, cervix, or breast);

    - Non-healed wound;

    - Prior adjuvant therapy for current melanoma diagnosis;

    - History of any clinically significant cardiovascular disorder (i.e., symptoms above
    Class II per New York Heart Association [NYHA] Functional Classification);

    - History of serious allergic reaction to yeast or yeast-derived products, including
    known or suspected hypersensitivity reaction to sargramostim;

    - Pregnant, breastfeeding, or planning to become pregnant during the study;

    - Received any other investigational therapy within 28 days of Day 1; or

    - Any concurrent medical condition that, in the opinion of the Investigator, would
    complicate or compromise compliance with the study or the well-being of the subject

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Summary of number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0,

    Secondary Outcome Measures

    Immune response by gamma interferon ElliSpot assay

    Trial Keywords

    HLA-A*02