Clinical Trials /

Nivolumab Plus Relatlimab in Patients With Metastatic Uveal Melanoma

NCT04552223

Description:

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.

Related Conditions:
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab Plus Relatlimab in Patients With Metastatic Uveal Melanoma
  • Official Title: A Phase 2 Study of Nivolumab + BMS-986016 (Relatlimab) in Patients With Metastatic Uveal Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 20200847
  • SECONDARY ID: CA224-094
  • NCT ID: NCT04552223

Conditions

  • Metastatic Uveal Melanoma

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab Plus Relatlimab Group
RelatlimabBMS-986016Nivolumab Plus Relatlimab Group

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Nivolumab Plus Relatlimab GroupExperimentalParticipants in this group will receive Nivolumab and Relatlimab administered together on Day 1 of every 4 week cycle. Both drugs will be administered until disease progression or intolerable toxicity for up to 24 months.
  • Nivolumab
  • Relatlimab

Eligibility Criteria

        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.

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:Objective response rate (ORR) will be the proportion of study participants with a confirmed complete response (CR) or partial response PR to study therapy as per treating physician evaluation using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Measure:Disease Control Rate (DCR)
Time Frame:Up to 24 months
Safety Issue:
Description:Disease control rate (DCR) is the proportion of patients with confirmed complete response (CR), partial response (PR), or stable disease (SD) as per treating physician evaluation using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 4 years
Safety Issue:
Description:Progression-free survival (PFS) is defined as the time from the date of enrollment to the date that objective progression disease is documented or death due to any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to 4 years
Safety Issue:
Description:Overall survival (OS) is defined as the time from the date of enrollment to the date of death.
Measure:Duration of Response (DOR)
Time Frame:Up to 4 years
Safety Issue:
Description:Duration of response is defined as the time from the date of first documented response (CR or PR) until date of documented progression or death in the absence of disease progression.
Measure:Proportion of Study Participants with Treatment-Related Toxicity
Time Frame:Up to 25 months
Safety Issue:
Description:The safety profile of the study therapy will be determined by the proportion of study participants experiencing treatment-related adverse events (AEs) and serious adverse events (SAEs). AEs and SAEs will be tabulated by type, grade, severity, treatment attribution according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jose Lutzky, MD

Trial Keywords

  • Metastatic Uveal Melanoma

Last Updated

September 11, 2020