Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
The purpose of this research is to test if a combination treatment of nivolumab and
relatlimab will result in tumor reduction in patients with metastatic uveal melanoma.
Phase
Phase 2
Funding Agency/Sponsor
Externally Peer-Reviewed
Disease
Cutaneous Malignancies
Enrollment Eligibility
Inclusion Criteria:
1. Have a biopsy-proven diagnosis of metastatic uveal melanoma, previously untreated with
anti-PD-1,Cytotoxic T lymphocyte antigen 4 (CTLA-4) and/or lymphocyte activation gene
3 (LAG-3) blocking antibodies.
2. Agree to undergo a pre-treatment and a post-treatment fresh biopsy of the tumor, if
easily accessible and low-risk.
3. 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.
Palliative radiation therapy to a limited field is allowed within this 3 week period.
4. Be willing and able to provide written informed consent/assent for the trial.
5. Be ≥ 18 years of age on day of signing informed consent.
6. Have measurable disease based on RECIST 1.1.
7. Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale.
8. Left Ventricular Ejection Fraction (LVEF) assessment with documented LVEF 50% by
either TTE or Multiple Gated Acquisition (MUGA) (TTE preferred test) within 6 months
from first study drug administration
9. Demonstrate adequate organ function as defined in Table 1. All screening labs should
be performed within 10 days of treatment initiation:
- Hematological:
- Absolute neutrophil count (ANC) ≥1,500 /microliter (mcL)
- Platelets ≥100,000 / mcL
- Hemoglobin ≥ 9 g/dL or ≥5.6 mmol/L (within 7 days of assessment)
- Renal:
- Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR
- Measured or calculated a creatinine clearance ≥30 mL/min for subject with
creatinine levels > 1.5 X institutional ULN (GFR can also be used in place
of creatinine or CrCl)
- Hepatic:
- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects
with total bilirubin levels > 1.5 ULN
- Aspartate Aminotransferase (AST) (SGOT) and Alanine Amino Transferase (ALT)
(SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
- Albumin ≥ 2.5 mg/dL
- Coagulation:
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤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.
- 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
- Creatinine clearance should be calculated per institutional standard.
10. 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.
11. If a female of childbearing potential, be willing to use an adequate method of
contraception as outlined in Section 5.8 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.
12. If a male of childbearing potential, agree to use an adequate method of contraception
as outlined in Section 5.8- 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:
1. 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.
2. 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.
3. Have a known history of active tuberculosis (Bacillus Tuberculosis)
4. Have had prior treatment with a PD-1 and/or LAG-3 targeted agent
5. Have hypersensitivity to nivolumab, relatlimab or any of their excipients.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Have known history of, or any evidence of active, non-infectious pneumonitis.
12. Have an active infection requiring systemic therapy.
13. 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.
14. Have known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. 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.
16. Have a diagnosis or known history of Human Immunodeficiency Virus (HIV), unless
controlled on antiretroviral drugs and have undetectable levels of HIV antibodies.
17. Have known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C.
18. Have received a live vaccine within 30 days of planned start of study therapy.
19. Have a history of myocarditis, regardless of etiology
20. Have a troponin T (TnT) or I (TnI)
- i) > 2x institutional upper limit of normal (ULN) : patient is excluded.
- ii) 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
21. Are patients with impaired decision-making capacity
22. 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).
23. Are compulsorily detained for treatment of either a psychiatric or physical (eg,
infectious disease) illness
24. 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.