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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02302339
Recruitment Status : Terminated (Development of glembatumumab vedotin was discontinued)
First Posted : November 27, 2014
Results First Posted : September 6, 2019
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics

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

Condition or disease Intervention/treatment Phase
Melanoma Drug: glembatumumab vedotin Drug: glembatumumab vedotin and varlilumab Drug: glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) Drug: glembatumumab vedotin and CDX-301 Phase 2

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. CDX-301 is a fully human protein that helps boost production of certain white blood cells. This protein allows the body's immune system to work against tumor cells.

Eligible patients who enroll in the study will receive treatment with one of the following: glembatumumab vedotin, glembatumumab vedotin and varlilumab, glembatumumab vedotin and CDX-301 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 132 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : November 2014
Actual Primary Completion Date : June 14, 2018
Actual Study Completion Date : October 3, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Glembatumumab vedotin
glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle.
Drug: glembatumumab vedotin
Other Name: Cohort 1

Experimental: Glembatumumab vedotin and varlilumab
glembatumumab 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.
Drug: glembatumumab vedotin and varlilumab
Other Name: Cohort 2

Experimental: Glembatumumab vedotin and PD-1 targeted checkpoint inhibitor
glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care.
Drug: glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)
Other Name: Cohort 3

Experimental: Glembatumumab vedotin and CDX-301
glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2.
Drug: glembatumumab vedotin and CDX-301
Other Name: Cohort 4




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Every 6 to 9 weeks following treatment initiation until disease progression. ]
    ORR is defined as the percentage of patients who achieved best overall response of complete or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions. ORR was the primary outcome for Cohorts 1-3 and a secondary outcome for Cohort 4.

  2. Adverse Events of the Combination of Glembatumumab Vedotin and CDX-301 (in Cohort 4). [ Time Frame: Up to 18 months following the screening visit ]
    The percentage of patients experiencing one or more adverse events.


Secondary Outcome Measures :
  1. Duration of Response (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. ]
    DOR is the number of months from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented per RECIST 1.1.

  2. Progression-free Survival (PFS) [ Time Frame: Evaluated every 6 to 9 weeks following treatment initiation until progression. ]
    PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or progression in a non-target lesion, or the appearance of new lesions.

  3. Overall Survival (OS) [ Time Frame: During treatment and every 3 months from end of treatment through death or end of study ]
    Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.

  4. Correlation of Activity to gpNMB Expression [ Time Frame: Up to 18 months following the screening visit ]
    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.

  5. 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, CDX-301 or PD-1 targeted checkpoint inhibitor (whichever occurs latest) ]
    The percentage of patients experiencing one or more AEs will be summarized by relationship to study drug and severity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Patients in Cohort 4 will submit a tumor tissue sample while on study.
  • 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)
  • Any non-study vaccination within 4 weeks, or influenza vaccine within 2 weeks, prior to CDX-301 dosing (Cohort 4 only)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02302339


Locations
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United States, California
The Angeles Clinic and Research Institute
Los Angeles, California, United States, 90025
Northern California Melanoma Center/St. Mary's Medical Center
San Francisco, California, United States, 94117
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33916
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
Florida Cancer Specialists
West Palm Beach, Florida, United States, 33407
United States, Georgia
Northside Hospital Cancer Institute
Atlanta, Georgia, United States, 30341
United States, Illinois
University of Chicago Medicine
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, New York
New York University School of Medicine
New York, New York, United States, 10016
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor Research Institute-Sammons Cancer Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Celldex Therapeutics
  Study Documents (Full-Text)

Documents provided by Celldex Therapeutics:
Study Protocol  [PDF] September 28, 2017
Statistical Analysis Plan  [PDF] January 22, 2018

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Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT02302339    
Other Study ID Numbers: CDX011-05
First Posted: November 27, 2014    Key Record Dates
Results First Posted: September 6, 2019
Last Update Posted: September 6, 2019
Last Verified: August 2019
Keywords provided by Celldex Therapeutics:
Advanced melanoma
Unresectable melanoma
Metastatic melanoma
Targeted Treatment for melanoma
GPNMB
CDX-011
Glembatumumab vedotin
Antibody-drug-conjugate
Skin neoplasm
Varlilumab
CDX-1127
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Nivolumab
Glembatumumab vedotin
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs