A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma
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|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
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||132 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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, 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.
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
|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|
|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|