Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab in Refractory Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02475213
Recruitment Status : Recruiting
First Posted : June 18, 2015
Last Update Posted : January 19, 2018
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Keytruda (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC), Urothelial Cancer and other B7-H3 expressing cancers. The study will also evaluate what is the highest dose of enoblituzumab that can be given safely when given with pembrolizumab. Assessments will also be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of MGA271 in combination with pembrolizumab.

Condition or disease Intervention/treatment Phase
Melanoma Head and Neck Cancer Non Small Cell Lung Cancer Urethelial Carcinoma Biological: Enoblituzumab Biological: Pembrolizumab Phase 1

Detailed Description:

This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up study of enoblituzumab administered intravenously (IV) on a weekly schedule for up to 51 doses in combination with IV pembrolizumab administered on an every-3-week schedule for up to 17 doses.

The dose escalation phase is designed to characterize the safety and tolerability of the combination of enoblituzumab and pembrolizumab and to define the maximum tolerated or maximum administered dose (MTD/MAD). Patients with methothelioma, urethelial cancer, NSCLC, SCCHN, clear cell renal cell carcinoma (ccRCC), ovarian cancer, melanoma, thyroid cancer, triple negative breast cancer (TBNC), pancreatic cancer, colon cancer, soft tissue sarcoma, or prostate cancer will be enrolled in this study phase.

During the Cohort Expansion Phase, additional cohorts of patients with B7-H3 expressing unresectable, locally-advanced or metastatic melanoma (up to n=16), 2 cohorts of NSCLC (n= up to 20 in each cohort), 2 cohorts of SCCHN (up to n=20 in each cohort) or urothelial cancer (up to n=16) will be enrolled to receive MGA271 in combination with pembrolizumab at the MTD (or MAD) established from the Dose Escalation Phase of the study.

The efficacy follow-up period consists of the 2-year period after the final dose of study drug.

All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination With Pembrolizumab in Patients With B7-H3-Expressing Melanoma, Squamous Cell Cancer of the Head and Neck, Non-Small Cell Lung Cancer and Other B7H3 Expressing Cancers
Study Start Date : July 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2020

Arm Intervention/treatment
Experimental: enoblituzumab plus pembrolizumab
Enoblituzumab: Fc-optimized, humanized monoclonal antibody. Pembrolizumab: Keytruda; human programmed death receptor-1 (PD-1)-blocking antibody approved by the US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor, or with advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express a protein called PD-L1. Keytruda is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, the first test designed to detect PD-L1 expression in non-small cell lung tumors.
Biological: Enoblituzumab
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Name: MGA271

Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Name: Keytruda

Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: one year ]
    Adverse Events, Serious Adverse Events

Secondary Outcome Measures :
  1. Peak plasma concentration [ Time Frame: 7 weeks ]
    PK of MGA271 in combination with pembrolizumab

  2. Number of participants that develop anti-drug antibodies [ Time Frame: One year ]
    Proportion of patients who develop anti-MGA271 antibodies, immunogenicity

  3. Change in tumor volume [ Time Frame: Weeks 6, 15, 24, 33, 42, 51 ]
    Anti-tumor activity of MGA271 in combination with pembrolizumab using both conventional RECIST 1.1 and immune-related RECIST criteria.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN, NSCLC, and other cancers that express B7-H3.
  • Melanoma that has progressed during or following at least 1 and up to 5 prior systemic treatments for unresectable locally advanced or metastatic disease, or melanoma patients who are intolerable of or have refused standard cancer therapy. Pre- and on-study biopsy required.
  • SCCHN that has progressed during or following at least 1 and up to 5 prior systemic treatments for metastatic or recurrent disease deemed to be incurable. Patient who refuse radical resection for recurrent disease or are intolerant of or refused standard first line therapy are eligible to enroll
  • NSCLC that has progressed during or following 1 - 5 prior systemic therapies for unresectable locally advanced or metastatic disease (at least one docetaxel, gemcitabine, or platinum analogue based therapy), or are intolerant of or refused standard cancer therapy. For squamous cell carcinoma, or adenocarcinoma without known activating mutation: the prior systemic therapy is at least one platinum analogue. For adenocarcinoma with known activating driver mutation: the prior systemic therapy is at least TKI directed
  • Urothelial cancer arising in the bladder, renal pelvis, ureter or urethra that has progressed during or following at least 1 and up to 5 prior systemic treatments for unresectable locally advanced or metastatic disease (includes anti-PD-L1,anti-PD-1, but excludes other experimental therapies). Patients must have received at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], dose-dense methotrexate/vinblastine/doxorubicin/cisplatin [DDMVAC], or carboplatinum/gemcitabine). No more than 5 prior systemic regimens allowed.
  • Measurable disease per RECIST 1.1 criteria
  • Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria:

  • Patients with a history of symptomatic central nervous system metastases, unless treated and asymptomatic
  • Patients with history of autoimmune disease with certain exceptions such as vitiligo, resolved chilhood atopic dermatitis, psoriasis not requiring systemic therapy within the past 2 years, patients with history of Grave's disease that are now euthyroid clinically and by lab testing
  • History of allogeneic bone marrow, stem cell, or solid organ transplant
  • Treatment with systemic cancer therapy or investigational therapy within 4 weeks of first study drug administration; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of first study drug administration
  • Trauma or major surgery within 4 weeks of first study drug administration
  • History of clinically-significant cardiovascular disease; gastrointestinal perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4 weeks of first study drug administration
  • Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration
  • Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction (PCR)
  • Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome
  • Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGA271 or pembrolizumab.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02475213

Contact: Rosetta Cavallo 240-552-8104

United States, Arizona
Mayo Clinic - AZ Not yet recruiting
Scottsdale, Arizona, United States, 85259
Principal Investigator: Ramesh Ramanathan, MD         
United States, Florida
Boca Raton Regional Hospital Not yet recruiting
Boca Raton, Florida, United States, 33486
Principal Investigator: Edgardo Santos Castillero, MD         
Mayo Clinic - FL Not yet recruiting
Jacksonville, Florida, United States, 32224
Principal Investigator: Yanyan Lou, MD, PhD         
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Kristina Trajic    813-745-4673 ext 1480   
Principal Investigator: Scott Antonia, MD         
United States, Kentucky
Norton Cancer Institute Research Program Active, not recruiting
Louisville, Kentucky, United States, 40202
United States, Maryland
University of Maryland Greenbaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Cheryl Young   
Principal Investigator: Dan Zandberg, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Tess Ferguson    617-632-1991   
Principal Investigator: Osama Rahma, MD         
United States, Michigan
South Texas Accelerated Research Therapeutics, LLC - Midwest Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Kathy Estkowski    616-954-5551   
Principal Investigator: Nehal Lakhani, MD, PhD         
United States, Minnesota
Mayo Clinic - MN Not yet recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Alex Adjei, MD, PhD         
United States, Nebraska
Nebraska Cancer Specialists Recruiting
Omaha, Nebraska, United States, 68130
Contact: Gladys Pierce    402-690-6972   
Principal Investigator: Ralph Hauke, MD         
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Kim Bradstreet, RN    702-952-3443   
Principal Investigator: Nicholas Vogelzang, MD         
United States, New York
Roswell Park Cancer Institute Not yet recruiting
Buffalo, New York, United States, 14263
Contact: Dawn DePaolo   
Principal Investigator: Gurkamal Chatta, MD         
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Molly McGuinness    212-304-5552   
Principal Investigator: Naiyer Rizvi, MD         
United States, Ohio
Gabrail Cancer Institute Not yet recruiting
Canton, Ohio, United States, 44718
Principal Investigator: Nashat Gabrail, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania/Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maryann Ghallagher, RN    215-662-7758   
Principal Investigator: Charu Aggarwal, MD         
University of Pittsburg Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Shea McQuilkin, BSN, RN    412-623-6650   
Principal Investigator: Robert Ferris, MD         
United States, Rhode Island
Rhode Island Hospital Not yet recruiting
Providence, Rhode Island, United States, 02903
Principal Investigator: Ariel Birnbaum, MD         
United States, South Carolina
Greenville Health System Not yet recruiting
Greenville, South Carolina, United States, 29605
Contact: Lisa Johnson    864-455-3735   
Principal Investigator: Jeffery Edenfield, MD         
United States, Texas
Mary Crowley Cancer Research Center Not yet recruiting
Dallas, Texas, United States, 75230
Principal Investigator: James Strauss, MD         
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Christina Duralde, RN, MSN    210-593-5242   
Principal Investigator: Anthony Tolcher, M.D.         
Sponsors and Collaborators
Study Director: James Vasselli, M.D. MacroGenics

Responsible Party: MacroGenics Identifier: NCT02475213     History of Changes
Other Study ID Numbers: CP-MGA271-03
First Posted: June 18, 2015    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by MacroGenics:
Malanoma, Non small cell lung cancer, SCCHN
Other B7-H3 expressing cancers

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Head and Neck Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents