AzTrials
AzTrials

MelanomaPhase 2NCT02302339

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

A Phase 2 study testing glembatumumab vedotin, glembatumumab vedotin and varlilumab and glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) in people with Melanoma, run by Celldex Therapeutics at 14 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
glembatumumab vedotin, glembatumumab vedotin and varlilumab and glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
132 participants
Where
14 sitesUnited States
Study dates
Nov 2014to 3 Oct 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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:
  • BRAF or MEK inhibitors within 2 weeks
  • Monoclonal based therapies within 4 weeks except for the PD-1 targeted checkpoint inhibitor in cohort 3
  • Immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks
Show all 21Show fewer
  • Chemotherapy within 21 days or at least 5 half-lives (whichever is longer)
  • 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:
  • Patients with adequately treated and cured non-melanoma skin cancer or in situ cancer
  • 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)

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Northside Hospital Cancer Institute

    Atlanta, Georgia, 30341

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Chicago Medicine

    Chicago, Illinois, 60637

  • Baylor Research Institute-Sammons Cancer Center

    Dallas, Texas, 75246

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Florida Cancer Specialists

    Fort Myers, Florida, 33916

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Mount Sinai Comprehensive Cancer Center

    Miami Beach, Florida, 33140

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • New York University School of Medicine

    New York, New York, 10016

  • Northern California Melanoma Center/St. Mary's Medical Center

    San Francisco, California, 94117

  • Florida Cancer Specialists

    West Palm Beach, Florida, 33407

Other trials in United States

About this study

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

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

Read the 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.

Conditions
Melanoma
Being tested
glembatumumab vedotin, glembatumumab vedotin and varlilumab, glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab), glembatumumab vedotin and CDX-301
Keywords
Advanced melanoma, Unresectable melanoma, Metastatic melanoma, Targeted Treatment for melanoma, GPNMB, CDX-011, Glembatumumab vedotin, Antibody-drug-conjugate, Skin neoplasm, Varlilumab, CDX-1127
Medical subject headings
Melanoma, Skin Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • glembatumumab vedotinDrug

    Also called Cohort 1

  • glembatumumab vedotin and varlilumabDrug

    Also called Cohort 2

  • glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)Drug

    Also called Cohort 3

  • glembatumumab vedotin and CDX-301Drug

    Also called Cohort 4

Study groups in NCT02302339
Study groupRoleWhat they receive
Glembatumumab vedotinExperimentalglembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle.
Receives: Drug: 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.
Receives: Drug: 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.
Receives: Drug: glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)
Glembatumumab vedotin and CDX-301Experimentalglembatumumab 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.
Receives: Drug: glembatumumab vedotin and CDX-301

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    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.

    Measured: Every 6 to 9 weeks following treatment initiation until disease progression.

  2. Adverse Events of the Combination of Glembatumumab Vedotin and CDX-301 (in Cohort 4).

    The percentage of patients experiencing one or more adverse events.

    Measured: Up to 18 months following the screening visit

Secondary outcomes (5)

  1. Duration of Response (DOR)

    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.

    Measured: 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.

  2. Progression-free Survival (PFS)

    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.

    Measured: Evaluated every 6 to 9 weeks following treatment initiation until progression.

  3. Overall Survival (OS)

    Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.

    Measured: During treatment and every 3 months from end of treatment through death or end of study

  4. Correlation of Activity to gpNMB Expression

    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.

    Measured: Up to 18 months following the screening visit

  5. Adverse Events

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

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2014 (estimated)
  2. Study startNov 2014
  3. Primary completion14 Jun 2018
  4. Study completion3 Oct 2018

Why it stopped: Development of glembatumumab vedotin was discontinued

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
132 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02302339
Sponsor's protocol ID
CDX011-05
Status last verified
Aug 2019
First submitted
19 Nov 2014
Last updated
6 Sep 2019
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing glembatumumab vedotin, glembatumumab vedotin and varlilumab and glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) in people with Melanoma, run by Celldex Therapeutics at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Every 6 to 9 weeks following treatment initiation until disease progression.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02302339.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in