Clinical Trials /

A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma

NCT02302339

Description:

This study will examine the effectiveness and safety of glembatumumab vedotin as monotherapy or in combination with immunotherapies in patients with advanced melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma
  • Official Title: A Phase 2 Study of Glembatumumab Vedotin, an Anti-gpNMB Antibody-drug Conjugate, as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma

Clinical Trial IDs

  • ORG STUDY ID: CDX011-05
  • NCT ID: NCT02302339

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
glembatumumab vedotinCohort 1Glembatumumab vedotin
glembatumumab vedotin and varlilumabCohort 2Glembatumumab vedotin and varlilumab
glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)Cohort 3Glembatumumab vedotin and PD-1 targeted checkpoint inhibitor

Purpose

This study will examine the effectiveness and safety of glembatumumab vedotin as monotherapy or in combination with immunotherapies in patients with advanced melanoma.

Detailed Description

      Glembatumumab vedotin consists of an antibody attached to a drug, monomethyl auristatin E
      (MMAE), that can kill cancer cells. The fully human antibody is designed to deliver the drug
      to cancer cells by attaching to a protein called glycoprotein NMB (gpNMB) that is expressed
      on the cancer cell. The MMAE is then released inside of the cell, where it interferes with
      cell growth and can lead to cell death of the targeted cell, as well as neighboring cells.
      Varlilumab is a fully human antibody that binds to CD27. This antibody allows the body's
      immune system to work against cancer cells. Nivolumab is a fully human antibody and
      pembrolizumab is a humanized antibody. Both bind to PD-1.

      Eligible patients who enroll in the study will receive treatment with one of the following:
      glembatumumab vedotin, glembatumumab vedotin and varlilumab or glembatumumab vedotin and
      either nivolumab OR pembrolizumab.

      All patients enrolled in the study will be closely monitored to determine if their cancer is
      responding to treatment and for any side effects that may occur.
    

Trial Arms

NameTypeDescriptionInterventions
Glembatumumab vedotinExperimentalglembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle.
  • glembatumumab vedotin
Glembatumumab vedotin and varlilumabExperimentalglembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10.
  • glembatumumab vedotin and varlilumab
Glembatumumab vedotin and PD-1 targeted checkpoint inhibitorExperimentalglembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care.
  • glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)

Eligibility Criteria

        Inclusion Criteria:

        Among other criteria, patients must meet all of the following conditions to be eligible for
        the study:

          -  Unresectable, histologically-confirmed advanced (Stage III or Stage IV) melanoma

          -  Disease progression during or after the last anticancer therapy received. For Cohort
             3, progression must have occurred during the PD-1 targeted CPI (checkpoint inhibitor)
             treatment and the investigator has deemed it appropriate to continue treatment with
             the PD-1 targeted CPI beyond confirmed disease progression

          -  No more than one prior chemotherapy-containing regimen for advanced disease.

          -  Prior treatments received must include at least one CPI inhibitor (e.g., Anti-CTLA-4,
             PD-1-, PD-L1-targeted immunotherapy) and for patients with a BRAF mutation at least
             one BRAF- or MEK-targeted therapy, unless patients are not candidates for, or refused,
             these therapies. For cohort 3, prior treatment received must include a PD-1 targeted
             CPI administered during the most recent disease progression and for patients with BRAF
             mutation at least one BRAF- or MEK-targeted therapy when appropriate

          -  The study site will submit paraffin-embedded tumor tissue obtained from the patient
             for gpNMB analysis. Patients may require a biopsy if recent tumor tissue is not
             available. Patients in cohort 2 and 3 must submit a recently obtained biopsy of the
             skin fold for gpNMB analysis.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1

          -  Adequate bone marrow, liver and renal function.

        Exclusion Criteria:

        Among other criteria, patients who meet any of the following conditions are NOT eligible
        for the study:

          -  Previously received glembatumumab vedotin (CR011-vcMMAE, CDX-011) or other
             MMAE-containing agents

          -  Treatment with the following therapies before the planned start of study treatment:

               1. BRAF or MEK inhibitors within 2 weeks

               2. Monoclonal based therapies within 4 weeks except for the PD-1 targeted checkpoint
                  inhibitor in cohort 3

               3. Immunotherapy (tumor vaccine, cytokine, or growth factor given to control the
                  cancer) within 2 weeks

               4. Chemotherapy within 21 days or at least 5 half-lives (whichever is longer)

               5. Investigational therapy within 2 weeks (or at least 5 half-lives, whichever is
                  longer)

          -  Patients with ocular melanoma

          -  Neuropathy that is moderate (Grade 2) or worse.

          -  Cancer that has spread to the brain or spine will be discussed with the study sponsor
             and may exclude patients from the trial.

          -  History of another cancer except:

               1. Patients with adequately treated and cured non-melanoma skin cancer or in situ
                  cancer

               2. Patients with any other cancer from which the patient has been disease-free for ≥
                  3 years

          -  Significant cardiovascular disease

          -  Previously received varlilumab or any other anti-CD27 mAb (Cohort 2 only)

          -  Active systemic infection requiring treatment

          -  Treatment with immunosuppressive medications within 4 weeks or corticosteroids within
             two weeks

          -  Patients with interstitial lung disease (Cohort 3 only)

          -  Patients with active diverticulitis (Cohort 3 only)
      
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:The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1, assessed up to 18 months.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of Response Rate (DOR)
Time Frame:From start date of partial or complete response (whichever is achieved first) to first date that recurrent of progressive disease is objectively documented, assessed up to 18 months.
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:From date of randomization to date of first documented progression or date of death from any cause whichever came first, assessed up to 18 months.
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From the first start date of protocol treatment to the date of death (whatever the cause), assessed up to 5 years.
Safety Issue:
Description:
Measure:Correlation of activity to gpNMB Expression
Time Frame:Up to 18 months following the screening visit
Safety Issue:
Description:To investigate if the anti-cancer activity of glembatumumab vedotin as monotherapy or in combination with immunotherapies in advanced melanoma is dependent upon the degree of gpNMB expression in tumor tissue.
Measure:Adverse Events
Time Frame:Following at least one dose of study treatment through 28 days after last dose of glembatumumab vedotin, or 70 calendar days after last administration of varlilumab or PD-1 targeted checkpoint inhibitor (whichever occurs latest)
Safety Issue:
Description:The percentage of patients experiencing one or more AEs will be summarized by relationship to study drug and severity.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celldex Therapeutics

Trial Keywords

  • Advanced melanoma
  • Unresectable melanoma
  • Metastatic melanoma
  • Targeted Treatment for melanoma
  • GPNMB
  • CDX-011
  • Glembatumumab vedotin
  • Antibody-drug-conjugate
  • Skin neoplasm
  • Varlilumab
  • CDX-1127

Last Updated

June 20, 2017