A Study of CDX-011 (CR011-vcMMAE) in Patients With Advanced GPNMB-expressing Breast Cancer (EMERGE)

A Phase II, Randomized, Multicenter Study of CDX-011 (CR011-vcMMAE) in Patients With Advanced GPNMB-expressing Breast Cancer

The main purpose of this study is to see whether CDX-011 is effective in treating patients who have advanced breast cancer that makes a protein called glycoprotein NMB (GPNMB), and who have already received (or were not candidates for) all available approved therapies for their breast cancer. This study will also further characterize the safety of CDX-011 treatment in this patient population.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: CDX-011; Drug: "Investigator's Choice" chemotherapy

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 effectiveness and safety of CDX-011 in patients with advanced breast cancer that makes the GPNMB protein. To better assess this, the effect of CDX-011 will be compared to treatment with currently available cancer chemotherapy.

Eligible patients who enroll in the study will be randomly assigned by chance to receive treatment with CDX-011 or with a chemotherapy chosen by their study doctor from a list of currently available drugs ("Investigator's Choice" chemotherapy). For each three patients enrolled, two will receive CDX-011 and one will receive treatment with "Investigator's Choice". Patients initially assigned to "Investigator's Choice" chemotherapy may be offered treatment with CDX-011 if their cancer worsens during this initial treatment.

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): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham Comprehensive Cancer Center
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • California
    • Long Beach, California, United States, 90806
      • Breastlink Medical Group
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Florida
    • West Coast, Florida, United States
      • Florida Cancer Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Georgia Cancer Specialists
    • Atlanta, Georgia, United States, 30318
      • Peachtree Hematology-Oncology Consultants PC
  • Illinois
    • Skokie, Illinois, United States, 60076
      • Orchard Healthcare Research Inc.
    • Zion, Illinois, United States, 60099
      • Cancer Treatment Centers of America at Midwestern Regional Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Cancer Care of Louisiana
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Montana
    • Missoula, Montana, United States, 59802
      • Montana Cancer Institute Foundation
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance Inc.
    • New York, New York, United States, 10065
      • Weill Cornell Breast Center/Weill Cornell Medical College
    • The Bronx, New York, United States, 10467
      • Montefiore-Einstein Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Cancer Institute/Blumenthal Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Clinic, Ltd.
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates
    • Sumter, South Carolina, United States, 29150
      • Santee Hematology Oncology, Inc.
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Center for Biomedical Research
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institution

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. 18 years of age or older.
2. Locally advanced or metastatic breast cancer.
3. Previous treatment with at least two but no more than seven prior chemotherapy treatments for progressive, recurrent or metastatic breast cancer.
4. Unless not a candidate for these agents, prior therapies must have included a taxane, an anthracycline, and capecitabine, as well as trastuzumab and lapatinib for patients whose tumors are positive for the human epidermal growth factor receptor 2 (HER2). (Patients who received incomplete courses of therapy with these agents due to intolerance will be eligible.)
5. Breast cancer tumor confirmed to express GPNMB. This will be determined by submitting a tissue sample (obtained during a diagnostic biopsy or surgery) to a central laboratory for analysis.

Exclusion Criteria:

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

1. Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are moderate (Grade 2) or worse in severity.
2. Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months.
3. Significant cardiovascular disease or any other underlying medical condition that, in the Investigator's opinion, will make the administration of study treatment (CDX-011 or chemotherapy) hazardous or would obscure the interpretation of side effects.

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
Experimental: CDX-011	Drug: CDX-011; CDX-011 (1.88 mg/kg) administered as an intravenous infusion on Day 1 of each 21 day cycle.
Active Comparator: "Investigator's Choice" chemotherapy	Drug: "Investigator's Choice" chemotherapy; Any of the following single-agent chemotherapy may be given at the discretion of the investigator, with a cycle length not to exceed four weeks: Capecitabine, Vinorelbine, Gemcitabine, Docetaxel, Paclitaxel, Albumin-bound paclitaxel, Doxorubicin HCL, Liposomal doxorubicin, Ixabepilone and Eribulin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guideline.	6 or more weeks following treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival is defined as the time from randomization to the earlier of disease progression or death due to any cause.	At least 18 months following treatment initiation
Adverse Events	The number and 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 "Investigator's Choice" chemotherapy and 3 to 4 weeks of follow-up)

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Publications and helpful links

General Publications

• Yardley DA, Weaver R, Melisko ME, Saleh MN, Arena FP, Forero A, Cigler T, Stopeck A, Citrin D, Oliff I, Bechhold R, Loutfi R, Garcia AA, Cruickshank S, Crowley E, Green J, Hawthorne T, Yellin MJ, Davis TA, Vahdat LT. EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer. J Clin Oncol. 2015 May 10;33(14):1609-19. doi: 10.1200/JCO.2014.56.2959. Epub 2015 Apr 6.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: June 30, 2010
• First Submitted That Met QC Criteria: July 2, 2010
• First Posted (Estimate): July 5, 2010

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: breast cancer; GPNMB; CDX-011; metastatic breast cancer; locally advanced breast cancer; Locally advanced or metastatic breast cancer; CR011-vcMMAE; Targeted treatment for breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Glembatumumab vedotin
• Other Study ID Numbers: CDX011-03