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

September 5, 2019 updated by: Celldex Therapeutics

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

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

132

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Cohort 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Every 6 to 9 weeks following treatment initiation until disease progression.
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.
Up to 18 months following the screening visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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: 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.
Evaluated every 6 to 9 weeks following treatment initiation until progression.
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.
During treatment and every 3 months from end of treatment through death or end of study
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.
Up to 18 months following the screening visit
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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celldex Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

June 14, 2018

Study Completion (Actual)

October 3, 2018

Study Registration Dates

First Submitted

November 19, 2014

First Submitted That Met QC Criteria

November 24, 2014

First Posted (Estimate)

November 27, 2014

Study Record Updates

Last Update Posted (Actual)

September 6, 2019

Last Update Submitted That Met QC Criteria

September 5, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDX011-05

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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