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

NCT ID: NCT02302339

Last Updated: 2019-09-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

132 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-30

Study Completion Date

2018-10-03

Brief Summary

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

Detailed Description

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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

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Melanoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Glembatumumab vedotin

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle.

Group Type EXPERIMENTAL

glembatumumab vedotin

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

glembatumumab vedotin and varlilumab

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

glembatumumab vedotin and CDX-301

Intervention Type DRUG

Interventions

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glembatumumab vedotin

Intervention Type DRUG

glembatumumab vedotin and varlilumab

Intervention Type DRUG

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

Intervention Type DRUG

glembatumumab vedotin and CDX-301

Intervention Type DRUG

Other Intervention Names

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Cohort 1 Cohort 2 Cohort 3 Cohort 4

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celldex Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Angeles Clinic and Research Institute

Los Angeles, California, United States

Site Status

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

San Francisco, California, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Site Status

Florida Cancer Specialists

West Palm Beach, Florida, United States

Site Status

Northside Hospital Cancer Institute

Atlanta, Georgia, United States

Site Status

University of Chicago Medicine

Chicago, Illinois, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

New York University School of Medicine

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Baylor Research Institute-Sammons Cancer Center

Dallas, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CDX011-05

Identifier Type: -

Identifier Source: org_study_id

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