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

This study is currently recruiting participants.
Verified June 2017 by Celldex Therapeutics
Sponsor:
ClinicalTrials.gov Identifier:
NCT02302339
First Posted: November 27, 2014
Last Update Posted: June 21, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Celldex Therapeutics
  Purpose
This study will examine the effectiveness and safety of glembatumumab vedotin as monotherapy or in combination with immunotherapies in patients with advanced melanoma.

Condition Intervention Phase
Melanoma Drug: glembatumumab vedotin Drug: glembatumumab vedotin and varlilumab Drug: glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:
  • 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. ]

Secondary Outcome Measures:
  • 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. ]
  • 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. ]
  • 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. ]
  • 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.

  • 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) ]
    The percentage of patients experiencing one or more AEs will be summarized by relationship to study drug and severity.


Estimated Enrollment: 120
Study Start Date: November 2014
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  • 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)
  Contacts and Locations
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


Contacts
Contact: Celldex Therapeutics info@celldex.com

Locations
United States, California
The Angeles Clinic and Research Institute Recruiting
Los Angeles, California, United States, 90025
Contact: Saba Mukarram    310-231-2121    smukarram@theangelesclinic.org   
Principal Investigator: Omid Hamid, MD         
Northern California Melanoma Center/St. Mary's Medical Center Recruiting
San Francisco, California, United States, 94117
Contact: Robert Weber, MD    415-750-5660    robert.weber@dignityhealth.org   
Contact: Lonnie Leonard, RN    415-750-4060    Lonnie.Leonard@DignityHealth.org   
Principal Investigator: Robert Weber, MD         
United States, Florida
Florida Cancer Specialists Recruiting
Fort Myers, Florida, United States, 33916
Contact: ask Sarah    877-691-7274    askSarah@scresearch.net   
Principal Investigator: Lowell Hart, MD         
Mount Sinai Comprehensive Cancer Center Recruiting
Miami Beach, Florida, United States, 33140
Contact: Yvonne Enriquez-Nunez    305-674-2625    yenrique@msmc.com   
Principal Investigator: Jose Lutzky, MD         
Florida Cancer Specialists Recruiting
West Palm Beach, Florida, United States, 33407
Contact: ask Sarah    877-691-7274    askSarah@scresearch.net   
Principal Investigator: Neal Rothschild, MD         
United States, Georgia
Northside Hospital Cancer Institute Recruiting
Atlanta, Georgia, United States, 30341
Contact: Charles Sykes, RN,OCN,CCRC    770-496-9418    charles.sykes@gacancer.com   
Principal Investigator: Aaron Alizadeh, MD         
United States, Illinois
University of Chicago Medicine Recruiting
Chicago, Illinois, United States, 60637
Contact: Jason J Luke, MD       JLuke@medicine.bsd.uchicago.edu   
Contact: Karen Matijevich, RN       KMatijev@medicine.bsd.uchicago.edu   
Principal Investigator: Jason J Luke, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Patrick Ott, MD    617-582-5030    Patrick_Ott@dfci.harvard.edu   
Contact: Kristina Kelley, RN    617-582-8687    Kristina_kelley@dfci.harvard.edu   
Principal Investigator: Patrick Ott, MD         
United States, Michigan
Henry Ford Hospital Terminated
Detroit, Michigan, United States, 48202
United States, New York
New York University School of Medicine Recruiting
New York, New York, United States, 10016
Contact: Mackenzie Tsang-Lee, RN    212-731-5682    Mackenzie.Tsang-Lee@nyumc.org   
Contact: Samantha Fields    212-263-4416    Samantha.Fields@nyumc.org   
Principal Investigator: Anna Pavlick, DO         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Shauna Eggerston, RN    919-668-3771      
Contact: April Salama, MD    919-613-0400      
Principal Investigator: April Salama, MD         
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: ask Sarah    877-691-7274    askSarah@scresearch.net   
Principal Investigator: David Spigel, MD         
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: VICC Clinical Trials Information Program    800-811-8480      
Principal Investigator: Douglas B. Johnson, MD         
United States, Texas
Baylor Research Institute-Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Lance Cowey, MD    214-818-8472    cancer.trials@baylorhealth.com   
Contact: Joyce Ghormley       joyce.ghormley@BSWHealth.org   
Principal Investigator: Lance Cowey, MD         
Sponsors and Collaborators
Celldex Therapeutics
  More Information

Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT02302339     History of Changes
Other Study ID Numbers: CDX011-05
First Submitted: November 19, 2014
First Posted: November 27, 2014
Last Update Posted: June 21, 2017
Last Verified: June 2017

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:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs