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This is a multicenter, phase II trial of relatlimab (rela), nivolumab (nivo), and ipilimumab (ipi) in patients with asymptomatic and symptomatic melanoma brain metastases.
Enrollment
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Inclusion and exclusion criteria
Inclusion Criteria:
Histologically confirmed non-uveal melanoma that has metastasized to the brain. At least 1 measurable intracranial target lesion (5-40mm) which was not previously treated with local therapy (no prior SRS to this lesion). Prior surgery for a brain metastasis is allowed but this lesion cannot be a target lesion.
a. 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.
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 for Cohort A (asymptomatic), ECOG performance status 0-2 for Cohort B (symptomatic)
No prior anti-CTLA-4, anti-PD-1, or anti-LAG-3 therapy for unresectable stage III/IV melanoma. Prior CTLA-4, PD-1, and/or LAG-3 therapy in the neoadjuvant or adjuvant setting is acceptable if >6 months since last treatment. Participants may have had prior BRAF+MEK inhibitors for adjuvant therapy and/or unresectable/metastatic melanoma if >2 weeks have elapsed since last treatment.
Adequate organ function as assessed by the following parameters:
Patients must have recovered from all prior anti-cancer therapy-related adverse events (AEs) to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v 5.0), except for alopecia, vitiligo, thyroid dysfunction, hypophysitis, or adrenal insufficiency, prior to enrollment.
Cohort A (asymptomatic): participants must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy greater than physiologic replacement (>10 mg of prednisone/day or equivalent) in the 10 days prior to beginning protocol therapy. Cohort B (symptomatic): participants may be on steroids with doses no higher than a total daily dose of 4 mg of dexamethasone or equivalent that is stable or tapering within 10 days prior to treatment. Patients who are symptomatic and are not being treated with steroids are also eligible.
Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to treatment.
Participants with a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection must have been treated and cured. Participants with HBV or HCV infection who are currently on treatment must have an undetectable HCV viral load prior to treatment.
Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) OR at least 4 unstained slides, with an associated pathology report, for testing of tumor PD-L1 expression:
Any radiation treatment or excision of non-target brain lesions must have occurred ≥ 1 weeks before the start of dosing for this study. NOTE: The radiation field must not have included the brain index lesion(s).
Radiation to non-CNS lesions is allowed and does not require a washout period for treatment initiation. Any radiation-related toxicity must have recovered to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v 5.0).
Women of child-bearing potential (WOCBP) must not be breastfeeding and must have a negative pregnancy test within 3 days prior to initiation of dosing. WOCBP (or female partners of male participants) must agree to use an acceptable method of birth control from the time of the negative pregnancy test, through the duration of treatment with the study combination and for 12 months after their last dose of any study component medication.
NOTE: A female participant is eligible to participate if she is not a woman of childbearing potential.
Approved methods of birth control are as follows:
Combined (estrogen and progesterone containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal Progesterone-only hormonal birth control associated with inhibition of ovulation: oral, injectable, implantable Intrauterine device (IUD) Intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Vasectomized partner True sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) is not acceptable
Patients (or legally authorized representative) must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC) and agree to abide by the study restrictions and return to the site for the required assessments.
Exclusion Criteria
Primary purpose
Allocation
Interventional model
Masking
60 participants in 2 patient groups
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Central trial contact
Allison Zhang
Data sourced from clinicaltrials.gov
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