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Trial record 1 of 1 for:    NCT02475213
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Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab in Refractory Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by MacroGenics
Sponsor:
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT02475213
First received: June 16, 2015
Last updated: September 26, 2016
Last verified: September 2016
  Purpose
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), 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 Intervention Phase
Melanoma
Head and Neck Cancer
Non Small Cell Lung Cancer
Mesothelioma
Urethelial Carcinoma
Clear Cell Renal Cell Carcinoma
Ovarian Cancer
Thyroid Cancer
Triple Negative Breast Cancer
Pancreatic Cancer
Colon Cancer
Soft Tissue Sarcoma
Prostate Cancer
Biological: Enoblituzumab
Biological: Pembrolizumab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by MacroGenics:

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


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

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

  • 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.


Estimated Enrollment: 75
Study Start Date: July 2015
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

In the cohort expansion phase, 3 cohorts of 16 patients each will be enrolled to further evaluate the safety and potential efficacy of the combination administered at the MTD/MAD dose in patients with melanoma, NSCLC, and SCCHN. Pre- and on-study biopsies are required for melanoma patients in the cohort expansion phase.

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).

  Eligibility

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

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
  • Mesothelioma that has progressed during or following at least 1 and up to 3 prior systemic treatments for unresectable locally advanced or metastatic disease. The prior systemic chemotherapy must have included a pemetrexed (anti-folate)-based regimen in combination with platinum agent. For patients in whom pemetrexed was contraindicated or not tolerated or not an approved therapy (e.g., peritoneal mesothelioma), prior therapy with a first-line platinum-based regimen is required.
  • 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.
  • Thyroid cancer that has progressed during or following at least 1 and up to 5 prior chemotherapy regimen(s). Prior therapy excludes experimental therapies given in Phase 1 trials.
  • Pancreatic cancer that has progressed during or following at least 1 and up to 3 prior chemotherapy regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.
  • Ovarian cancer that has progressed during or following at least 2 and up to 4 prior therapeutic regimens (e.g., 2 prior platinum containing regimens or if platinum resistant, a liposomal doxorubicin or topotecan containing regimen). Prior therapy excludes experimental therapies given in Phase 1 trials
  • Colon cancer that has progressed during or following at least 2 and up to 4 prior therapeutic regimens (e.g., fluoropyrimidine and/or irinotecan and/or oxaliplatin and/or anti-EGFR antibody containing regimens). Prior therapy excludes experimental therapies given in Phase 1 trials.
  • Prostate cancer that has progressed during or following at least 1 and up to 5 prior therapeutic regimens (e.g., abiraterone, enzalutamide, docetaxel). Prior therapy excludes experimental therapies given in Phase 1 trials.
  • Soft tissue sarcoma that has progressed during or following at least 1 and up to 5 prior therapeutic regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.
  • TNBC that has progressed during or following at least 1 and up to 5 prior therapeutic regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.
  • ccRCC that has progressed during or following at least 1 and up to 5 prior therapeutic regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02475213

Contacts
Contact: Soyoung Yun 240 552-8058 yuns@macrogenics.com

Locations
United States, Florida
Moffitt Cancer Center Active, not recruiting
Tampa, Florida, United States, 33612
United States, Maryland
University of Maryland Greenbaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Shirley George       shirleygeorge@umm.edu   
Principal Investigator: Dan Zandberg, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Molly McGuinness    212-304-5552    mm5016@cumc.columbia.edu   
Principal Investigator: Naiyer Rizvi, 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    maryann.gallagher@uphs.upenn.edu   
Contact: , RN         
Principal Investigator: Charu Aggarwal, MD         
University of Pittsburg Recruiting
Pittsburg, Pennsylvania, United States
Contact: Shea McQuilkin, BSN, RN    412-623-6650    mcquilkinm@upmc.edu   
Principal Investigator: Robert Ferris, MD         
United States, Texas
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Christina Duralde, RN, MSN    210-593-5242    christina.duralde@start.stoch.com   
Principal Investigator: Anthony Tolcher, M.D.         
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: James Vasselli, M.D. MacroGenics
  More Information

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02475213     History of Changes
Other Study ID Numbers: CP-MGA271-03
Study First Received: June 16, 2015
Last Updated: September 26, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by MacroGenics:
Malanoma, Non small cell lung cancer, SCCHN
Other B7H3 expressing cancers

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma
Pancreatic Neoplasms
Head and Neck Neoplasms
Carcinoma, Renal Cell
Mesothelioma
Thyroid Neoplasms
Sarcoma
Triple Negative Breast Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
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
Neoplasms, Glandular and Epithelial
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases

ClinicalTrials.gov processed this record on March 23, 2017