An Investigational Immuno-therapy Study to Evaluate Safety and Effectiveness in Patients With Melanoma That Has Spread to the Brain, Treated With Nivolumab in Combination With Ipilimumab, Followed by Nivolumab by Itself
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Ipilimumab; Nivolumab
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 119.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study of Nivolumab combined with Ipilimumab followed by Nivolumab by itself for the
      treatment of patients with Melanoma that has spread to the brain. Patients with
      histologically confirmed Malignant Melanoma and asymptomatic brain metastases are eligible
      for the study.
    

Eligibility criteria:

        For more information regarding BMS clinical trial participation, please visit
        www.BMSStudyConnect.com

        Inclusion Criteria:

        1. Target Population

          1. Histologically confirmed malignant melanoma with measurable metastases in the brain.
             Both asymptomatic and symptomatic patients.

          2. Cohort A (asymptomatic patients): At least 1 measurable brain metastasis ≥ 0.5 cm in
             and ≤ 3 cm in longest diameter that has not been previously irradiated. No clinical
             requirement for local intervention (surgery, radiosurgery, corticosteroid therapy) or
             other systemic therapy

             Cohort B (symptomatic patients): Subjects with neurologic signs and symptoms related
             to metastatic brain lesions are eligibile. Subjects must have at least 1 measurable
             brain metastasis ≥ 0.5 cm in and ≤ 3 cm in longest diameter that has not been
             previously irradiated. No immediate requirement (within 3 weeks prior to first
             treatment) for local intervention (surgery, radiosurgery, corticosteroid therapy).
             Steroid use is permitted as defined in the protocol.

          3. Prior stereotactic radiotherapy (SRT) and prior excision of up to 3 melanoma brain
             metastases is permitted if there has been complete recovery, with no neurologic
             sequelae, and measurable lesions remain. Growth or change in a lesion previously
             irradiated will not be considered measurable. Regrowth in cavity of previously excised
             lesion will not be considered measurable. lesions or prior excision must have occurred
             ≥ 3 weeks before the start of dosing for this study

          4. Must have tumor tissue available for biomarker analysis. Biopsy should be excisional,
             incisional, punch, or core needle

          5. Cohort A (asymptomatic): Subjects must be free of neurologic signs and symptoms
             related to metastatic brain lesions and must not have required or received systemic
             corticosteroid therapy within 10 days prior to first treatment.

             Cohort B (symptomatic): Subjects with neurologic signs and symptoms related to
             metastatic brain lesions are eligible per Amendment 02. Subjects with neurologic signs
             and symptoms may be treated with a total daily dose of no more than 4 mg of
             dexamethasone that is stable or tapering for 10 days prior to first treatment.
             Subjects with neurologic signs and symptoms who are not being treated with steroids
             are eligible for Cohort B and should have no experience of seizure within 10 days
             prior to first treatment.

          6. Allowable prior therapy:

               1. Approved adjuvant therapies, which may include molecularly-targeted agents, IFN
                  α, and ipilimumab. Patients who received ipilimumab as adjuvant therapy must have
                  a 6 month washout before receiving any dosing on this study

               2. For advanced disease, interleukin-2 at any dose and/or IFN-α (any formulation, no
                  washout required); MEK and BRAF inhibitors: washout for at least 4 weeks prior to
                  the start of dosing in this study

               3. Steroids for physiological replacement are allowed.

          7. Cohort A (asymptomatic): ECOG performance status ≤1 Cohort B (symptomatic): ECOG
             performance status ≤2

        Exclusion Criteria:

        2. Target Disease Exceptions

          1. History of known leptomeningeal involvement (lumbar puncture not required)

          2. Previous stereotactic or highly conformal radiotherapy within 3 weeks before the start
             of dosing for this study. Note the stereotactic radiotherapy field must not have
             included the brain index lesion(s)

          3. Brain lesions >3 lesions which were previously treated with SRT

          4. Brain lesion size > 3cm 3. Medical History and Concurrent Diseases

        a) History of whole brain irradiation b) Subjects with an active, known or suspected
        autoimmune disease c) Subjects with major medical, neurologic or psychiatric condition who
        are judged as unable to fully comply with study therapy or assessments should not be
        enrolled d) Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in
        situ of the cervix. For any prior invasive malignancy, at least 5 years must have elapsed
        since curative therapy and patients must have no residual sequelae of prior therapy e)
        Cohort A (asymptomatic): The use of corticosteroids is not allowed within 10 days prior to
        first treatment (based upon 5 times the expected half life of dexamethasone) except
        patients who are taking steroids for physiological replacement. If alternative
        corticosteroid therapy has been used, consultation with the sponsor Medical Monitor is
        required to determine the washout period prior to initiating study treatment Cohort B
        (symptomatic): Subjects with neurologic sign and symptoms related to brain metastases who
        are being treated with a total daily dose of higher than 4 mg dexamethasone or equivalent
        within 10 prior to the start of treatment with study drug are excluded.

        4. Physical and Laboratory Test Findings

          1. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
             ribonucleic acid (HCV antibody) indicating acute or chronic infection

          2. Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on ART-due to
             the unknown effects of HIV on the immune response to combined nivolumab plus
             ipilimumab or the unique toxicity spectrum of these drugs in patients with HIV

             5. Allergies and Adverse Drug Reaction

        a) History of allergy to study drug components b) History of severe hypersensitivity
        reaction to any monoclonal antibody

        6. Other Exclusion Criteria

          1. Prisoners or subjects who are involuntarily incarcerated

          2. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness Eligibility criteria for this study have
             been carefully considered to ensure the safety of the study subjects and that the
             results of the study can be used. It is imperative that subjects fully meet all
             eligibility criteria

        Other protocol defined inclusion/exclusion criteria could apply