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Nivolumab and Relatlimab for the Treatment of Metastatic Uveal Melanoma

Trial Status: Active

This phase II trial studies how well nivolumab and relatlimab work in treating patients with uveal melanoma that has spread to other places in the body (metastatic). Nivolumab is thought to work by turning off the activity of PD-1 (programmed death-1), which is a protein found on T cells (a type of immune cell) that helps keep the body’s immune responses in check. When PD-1 is blocked, it is thought that the ability of T cells to kill cancer cells is increased. Relatlimab is thought to work by turning off the activity of LAG-3 (lymphocyte activation gene-3), which is a protein found on tumor infiltrating lymphocytes (TIL), a type of immune cell. When LAG-3 is blocked it is thought that TIL cell’s ability to attack cancer cells is increased, thereby reducing tumor growth. Giving nivolumab and relatlimab may increase the ability of the immune system to attack tumor cells in patients with metastatic uveal melanoma.

Inclusion Criteria

  • Have a biopsy-proven diagnosis of metastatic uveal melanoma, previously untreated with anti-PD-1,CTLA-4 and/or LAG-3 blocking antibodies
  • Agree to undergo a pre-treatment and a post-treatment fresh biopsy of the tumor, if easily accessible and low-risk
  • Have completed all previous therapy for a minimum of 3 weeks before the first dose of experimental treatment. All adverse events of previous therapy must have resolved
  • Be willing and able to provide written informed consent/assent for the trial
  • Be >= 18 years of age on day of signing informed consent
  • Have measurable disease based on RECIST 1.1
  • Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Left ventricular ejection fraction (LVEF) assessment with documented LVEF > 50% by either transthoracic echocardiography (TTE) or multigated acquisition (MUGA) (TTE preferred test) within 6 months from first study drug administration
  • Absolute neutrophil count (ANC) >= 1,500 /mcL (performed within 10 days of treatment initiation)
  • Platelets >= 100,000 / mcL (performed within 10 days of treatment initiation)
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (within 7 days of assessment) (performed within 10 days of treatment initiation)
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 10 days of treatment initiation) * Creatinine clearance should be calculated per institutional standard
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 10 days of treatment initiation)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (performed within 10 days of treatment initiation)
  • Albumin >= 2.5 mg/dL (performed within 10 days of treatment initiation)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants(performed within 10 days of treatment initiation)
  • If a female of childbearing potential, have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • If a female of childbearing potential, be willing to use an adequate method of contraception, for the course of the study through 24 weeks after the last dose of study medication. Must abstain from ova donation for a minimum of 5 months after the end of treatment * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
  • If a male of childbearing potential, agree to use an adequate method of contraception, starting with the first dose of study therapy through 7 months after the last dose of study therapy. Must abstain from sperm donation for a minimum of 24 weeks after the end of treatment * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria

  • Are currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of the first dose of treatment
  • Have a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on replacement doses of corticosteroids and patients who received steroids as pre-medication to prevent an imaging contrast allergy are allowed
  • Have a known history of active tuberculosis (Bacillus tuberculosis)
  • Have had prior treatment with a PD-1 and/or LAG-3 targeted agent
  • Have hypersensitivity to nivolumab, relatlimab or any of their excipients
  • Have had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from clinically significant adverse events due to agents administered more than 3 weeks earlier
  • Have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from clinically significant adverse events due to a previously administered agent * Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * Note: Patients will be allowed necessary and palliative radiation therapy to limited fields during the trial, as long as it does not encompass a target lesion
  • Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, ductal carcinoma in situ (DCIS), incidentally discovered asymptomatic thyroid cancer, prostate-specific antigen (PSA) recurrence of prostate cancer stable on hormonal therapy with no otherwise detectable disease, and a previous diagnosis of malignancy that has shown no evidence of disease progression for 5 years or longer
  • Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis as well as a history of previous or current significant brain hemorrhage. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids to treat edema for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which will be excluded regardless of clinical stability
  • Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Have known history of, or any evidence of active, non-infectious pneumonitis
  • Have an active infection requiring systemic therapy
  • Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Have a diagnosis or known history of human immunodeficiency virus (HIV), unless controlled on antiretroviral drugs and have undetectable levels of HIV antibodies
  • Have known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C
  • Have received a live vaccine within 30 days of planned start of study therapy
  • Have a history of myocarditis, regardless of etiology
  • Have a troponin T (TnT) or I (TnI) * > 2 x institutional upper limit of normal (ULN) : patient is excluded * Between > 1 to 2 x ULN enrollment will be permitted if a repeat assessment remains =< 2 x ULN and participant undergoes a cardiac evaluation and is cleared by a cardiologist or cardio-oncologist
  • Are patients with impaired decision-making capacity
  • Are prisoners or participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included as a participant. Strict conditions apply and Bristol-Myers Squibb approval is required)
  • Are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
  • Have psychological, familial, sociological, or geographical conditions that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the participant before registration in the trial

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: ACTIVE
Contact: Jose Lutzky
Phone: 305-689-4037

PRIMARY OBJECTIVE:

I. To evaluate efficacy of the combination of nivolumab and relatlimab (BMS-986016) in terms of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

SECONDARY OBJECTIVE:

I. To evaluate the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety profile of the combination of nivolumab and BMS-986016.

EXPLORATORY OBJECTIVES:

I. Tumor microenvironment (TME) in fresh biopsies pre- and post-treatment and at progression.

II. Blood samples at baseline and predetermined post-treatment time points and at progression.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 60 minutes and relatlimab IV over 60 minutes on day 1. Cycles repeat 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 12 weeks for 2 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Miami Miller School of Medicine-Sylvester Cancer Center

Principal Investigator
Jose Lutzky

  • Primary ID 20200847
  • Secondary IDs NCI-2020-11454, CA224-094
  • Clinicaltrials.gov ID NCT04552223