Study of Glembatumumab Vedotin (CDX-011) in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (METRIC)

A Randomized Multicenter Pivotal Study of CDX-011 (CR011-vcMMAE)in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (The METRIC Study)

The main purpose of this study is to see whether CDX-011 (glembatumumab vedotin, an antibody-drug conjugate) is effective in treating patients who have advanced Triple-Negative Breast Cancer (TNBC), and whose tumor cells make a protein called glycoprotein NMB (gpNMB), which CDX-011 binds to. The study will also further characterize the safety of CDX-011 treatment in this patient population.

Study Overview

• Status: Completed
• Conditions: Metastatic gpNMB Over-expressing Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: CDX-011

Detailed Description

CDX-011 consists of an antibody attached to a drug, monomethyl auristatin E (MMAE), that can kill cancer cells. The antibody delivers 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 may lead to cell death.

This study will examine the efficacy and safety of CDX-011 in patients with advanced TNBC that makes the gpNMB protein. The effect of CDX-011 will be compared to treatment with capecitabine.

Eligible patients who enroll in the study will be randomly assigned (by chance) to receive treatment with CDX-011 or with capecitabine. For every three patients enrolled, two will receive CDX-011 and one will receive treatment with capecitabine. 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): 327
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincents Hospital Sydney
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University
    • Tweed Heads, New South Wales, Australia, 2485
      • The Tweed Hospital
    • Wahroonga, New South Wales, Australia, 2076
      • Sydney Adventist Hospital
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Townsville Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Footscray, Victoria, Australia, 3011
      • Western Hospital
    • Heidelberg, Victoria, Australia, 3084
      • Joint Ludwig-Austin Dept of Medical Oncology
    • Richmond, Victoria, Australia, 3121
      • Epworth Health Care
• Belgium
  • Brussels Capital Region, Belgium, 1180
    • Clinique Edith Cavell
  • Bruxelles, Belgium, 1000
    • Institute Jules Bordet
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium, 2610
      • GasthuisZusters Antwerpen
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Grand Hopital de Charleroi asbl
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Canada
  • Ontario
    • Sault Ste Marie, Ontario, Canada, P6B-0A8
      • Algoma District Cancer Program Sault Area Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre Odette Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B Davis Jewish General Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Universite de Montreal-Hopital Du Sacre-Coeur De Montreal
• France
  • Avignon, France, 84000
    • Institut Sainte Catherine
  • Lille, France, 59000
    • Centre OSCAR LAMBRET
  • Lyon, France, 69317
    • Hôpital de La Croix Rousse
  • Mont de Marsan, France, 40000
    • Centre Hospitalier de Mont de Marson - Hôpital Layné
  • Paris, France, 75005
    • Institut Curie
  • Pierre Benite, France, 69495
    • Hospices Civils de Lyon
  • St Gregoire, France, 35768
    • Centre Hospitalier Prive Saint-Gregoire
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06189
      • Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer
  • Rhône
    • Lyon, Rhône, France, 69373
      • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
  • Sarthe
    • Le Mans, Sarthe, France, 72000
      • Centre Jean Bernard Clinique Victor Hugo
• Germany
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin Buch
  • Cologne, Germany, 51067
    • Kliniken der Stadt Koeln gGmbH - Krankenhaus Holweide
  • Düsseldorf, Germany, 40225
    • Universitatsklinikum Dusseldorf
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Frankfurt am Main, Germany, 65929
    • Klinikum Frankfurt Höchst GmbH
  • Halle, Germany, 06120
    • Martin-Luther-Universität Halle-Wittenberg
  • Homberg, Germany, 66421
    • Universität des Saarlandes
  • Munich, Germany, 80637
    • Rotkreuzklinikum Munchen
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Troisdorf, Germany, 53840
    • Hämatologisch-Onkologische Schwerpunktpraxis
  • Baden-Wurttemberg
    • Esslingen Am Neckar, Baden-Wurttemberg, Germany, 73730
      • Klinikum Essingen GmbH
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
  • Torino, Italy, 10126
    • Azienda Ospedaliera Citta della Salute e della Scienza de Torino
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Istituto Scientifico romagnolo Per Lo Studio E La Cura Del Tumori IRST
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A Gemelli
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Istituto Europeo Di Oncologia
    • Milano, Lombardia, Italy, 20133
      • Istituto Nazionale dei Tumori
    • Milano, Lombardia, Italy, 20121
      • Azienda Ospedaliera Fatebenefratelli e Oftaimico
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Centro di Riferimento Oncologico
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • Azienda Ospedaliera Universitaria Pisana
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center Madrid-Espana
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
  • Castellón
    • Castellon de La Plana, Castellón, Spain, 12002
      • Consorcio Hospitalario Provincial de Castellón
  • Communidad Delaware
    • Madrid, Communidad Delaware, Spain, 28034
      • Hospital Universitario Ramon y Cajal
  • Málaga
    • Malaga, Málaga, Spain, 29011
      • Hospital Regional Universitario de Málaga - Hospital General
• United Kingdom
  • City of London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
  • City Of London
    • London, City Of London, United Kingdom, EC1A 7BE
      • Barts Health Nhs Trust
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Derriford Hospital
  • East Sussex
    • Brighton, East Sussex, United Kingdom, BN2 5BE
      • Royal Sussex County Hospital
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G12 0YN
      • Beatson West of Scotland Cancer Centre
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Blackpool Victoria Hospital
  • London, City Of
    • London, London, City Of, United Kingdom, NW1 2PG
      • University College London
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham University Hospitals Nhs Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35211
      • Alabama Oncology
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Cancer Research Insititute
  • Arizona
    • Glendale, Arizona, United States, 85304
      • Arizona Cancer Research Alliance
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Medical Group
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center and Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • Salinas, California, United States, 93901
      • Pacific Cancer Care
    • San Francisco, California, United States, 94115
      • University of California San Francisco
    • Vallejo, California, United States, 94589
      • Kaiser Permaente
    • West Hills, California, United States, 91307
      • Wellness Hematology Oncology
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami Miller School of Medicine
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists South
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Specialists
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial HealthCare
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
    • Atlanta, Georgia, United States, 30318
      • Peachtree Hematology Oncology Consultants, PC
    • Atlanta, Georgia, United States, 30341
      • Georgia Cancer Specialists Clinic
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers P.C.
    • Savannah, Georgia, United States, 31405
      • Summit Cancer Care, PC-Savannah
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Harvey, Illinois, United States, 60426
      • Ingalis Memorial Hospital
    • Peoria, Illinois, United States, 60615
      • Illinois CancerCare
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research Inc.
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Lafayette General Medical Center
    • Marrero, Louisiana, United States, 70072
      • Hematology and Oncology Specialists
    • New Orleans, Louisiana, United States, 70121
      • Oschner Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health New Orleans
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287-0013
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital
    • Silver Spring, Maryland, United States, 20902
      • Holy Cross Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Center
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Health
    • Saint Louis, Missouri, United States, 63141
      • St John's Mercy Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University Dept of Oncology
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Regional Cancer Center
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance, Inc.
    • Lake Success, New York, United States, 11042
      • ProHEALTH Care Associates
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center
    • New York, New York, United States, 10011
      • Beth Isreal Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic-Taussig Cancer Institute-R35
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical Research Center, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Clinic of Oklahoma
  • Oregon
    • Beaverton, Oregon, United States, 97006
      • Oregon Health and Science University
  • Pennsylvania
    • Langhorne, Pennsylvania, United States, 19047
      • St Mary Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates (CHOA)
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology Hematology Associates
    • Knoxville, Tennessee, United States, 37909
      • Center for Biomedical Research, LLC
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Oncology Hematology Consultants PA
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

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:

1. Diagnosed with metastatic (i.e., cancer that has spread) TNBC

   • minimal or no expression of estrogen and progesterone receptors (ER/PR) <10% of cells positive by immunohistochemistry
   • HER 2 staining 0 or 1+ by IHC or copy number <4.0 signals/cell
2. Documented progression of disease based on radiographic, clinical or pathologic assessment during or subsequent to the last anticancer regimen received.
3. Breast cancer tumor confirmed to express gpNMB. This will be determined by submitting a tissue sample from the advanced (locally advanced/recurrent or metastatic) disease setting to a central laboratory for analysis.
4. Received no more than two prior chemotherapy treatments for advanced (locally advanced/recurrent or metastatic) breast cancer.
5. Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or Doxil) if clinically indicated and a taxane (eg: Taxol).
6. ECOG performance status of 0 - 1.
7. Adequate bone marrow, liver and renal function.

Exclusion:

Among other criteria, patients who meet any of the following conditions are NOT eligible for the study:

1. Progression/recurrence of breast cancer during or within 3 months of completion of neoadjuvant or adjuvant chemotherapy.
2. Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are moderate (Grade 2) or worse in severity.
3. Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months.
4. Significant cardiovascular disease.
5. Previously received capecitabine and discontinued due to progression or intolerance; previously received CDX-011 or other MMAE containing agents.
6. Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary.
7. Chronic use of systemic corticosteroids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Capecitabine; Capecitabine will be administered on Days 1 through 14 of each 21 day cycle.	Drug: Capecitabine
Experimental: Drug: CDX-011; CDX-011 administered as an intravenous infusion on Day 1 of each 21 day cycle.	Drug: CDX-011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. The primary analysis of PFS was based on PFS events determined retrospectively by the central independent review committee, blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria.	Evaluated every 6 - 9 weeks following treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of patients who achieve best overall response of complete or partial response. The analysis of ORR was based on ORR events determined retrospectively by the central independent review committee, blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.	Evaluated every 6 - 9 weeks following treatment initiation
Duration of Response	Duration of response (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. The analysis of DOR was determined retrospectively by the central independent review committee,blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.	Evaluated every 6 - 9 weeks following treatment initiation
Overall Survival	Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.	During treatment and 3 months from end of treatment through end of study or approximately up to 5 years.
Adverse Events (AE)	The percentage of patients experiencing one or more adverse events will be summarized by treatment arm, relationship to study drug, and severity.	Usually following at least 1 cycle of study treatment (1 dose of CDX-011 or capecitabine and until discontinuation of follow-up)
Pharmacokinetics (PK)	Concentration of the antibody drug conjugate (ADC), total antibody (TA) and free MMAE will be determined.	Following 1 dose of CDX-011.

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): November 30, 2017
• Study Completion (Actual): August 7, 2018

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: November 27, 2013
• First Posted (Estimate): November 28, 2013

Study Record Updates

• Last Update Posted (Actual): March 8, 2019
• Last Update Submitted That Met QC Criteria: March 6, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Breast cancer; TNBC; Triple Negative Breast Cancer; Metastatic Breast Cancer; Breast Neoplasms; CDX-011; Glembatumumab vedotin; Antibody-drug-conjugate; Progesterone; Triple negative; Locally advanced breast cancer; Estrogen; Targeted treatment for breast cancer; HER2 receptors; gpNMB; METRIC
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: CDX011-04