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Enoblituzumab (MGA271) in Children With B7-H3-expressing Solid Tumors

This study is currently recruiting participants.
Verified September 2017 by MacroGenics
Sponsor:
ClinicalTrials.gov Identifier:
NCT02982941
First Posted: December 6, 2016
Last Update Posted: September 19, 2017
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.
Information provided by (Responsible Party):
MacroGenics
  Purpose
This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or refractory malignant solid tumors.

Condition Intervention Phase
Neuroblastoma Rhabdomyosarcoma Osteosarcoma Ewing Sarcoma Wilms Tumor Desmoplastic Small Round Cell Tumor Drug: Enoblituzumab Phase 1

Study Type: Interventional
Study Design: 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 Pediatric Patients With B7-H3-Expressing Relapsed or Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • Safety and tolerability of enoblituzumab. [ Time Frame: Time of first dose through end of treatment (up to 2 years) ]
    Adverse events, SAEs, incidence of treatment-emergent AE


Secondary Outcome Measures:
  • Peak plasma concentration [ Time Frame: Time of first dose through end of treatment (up to 96 weeks) ]
    PK of enoblituzumab

  • Number of participants that develop anti-drug antibodies [ Time Frame: Time of first dose through end of treatment (up to 96 weeks) ]
    Proportion of patients who develop anti-MGA271 antibodies, immunogenicity

  • Antitumor activity of enoblituzumab [ Time Frame: Time of first dose through end of treatment (up to 96 weeks) ]
    Anti-tumor activity of enoblituzumab using conventional RECIST 1.1 and immune related RECIST criteria


Estimated Enrollment: 112
Study Start Date: December 2016
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation & Cohort Expansion
enoblituzumab administered IV weekly
Drug: Enoblituzumab
enoblituzumab administered IV weekly for up to 96 weeks
Other Name: MGA271

Detailed Description:

This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or refractory malignant solid tumors.

The study consists of a Dose Escalation Phase to determine the MTD (or MAD) of enoblituzumab followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of enoblituzumab. In the cohort expansion phase, 5 cohorts of 10 patients each will be enrolled to further evaluate the safety and potential efficacy of enoblituzumab administered at the MTD/MAD in patients with:1) neuroblastoma - measurable disease, 2) neuroblastoma - non-measurable disease, 3) rhabdomyosarcoma, 4) osteosarcoma, and 5) Ewing's sarcoma, Wilms' tumor and desmoplastic small round cell tumors.

All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC). Disease assessment in patients with neuroblastoma will use neuroblastoma overall response criteria.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

General Inclusion Criteria:

  • Age ≥ 1 to 21 years at diagnosis of primary tumor (treatment up to the age of 30 years old).
  • Relapsed or refractory malignant solid tumors of any histology for which no standard curative therapy is available (escalation phase).
  • Histologically proven: neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma/ primitive neuroectodermal tumor, Wilms tumor, desmoplastic small round cell tumor (cohort expansion phase).
  • Must have malignant solid tumors that demonstrate B7-H3 expression at 2+ or greater levels on the membranous surface of at least 10% of tumor cells or ≥ 25% of tumor vasculature by IHC.
  • With the exception of patients with non-measurable neuroblastoma patients must have measurable disease as per RECIST 1.1
  • Karnofsky (patients > 16 years)/Lansky (patients ≤ 16 years) index ≥ 70.
  • Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria:

  • Patients are to be excluded from the study if they have any of the following:
  • Patients with a history of symptomatic central nervous system (CNS) unless they have been treated and are asymptomatic.
  • Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment within the past 2 years, and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
  • History of prior allogeneic bone marrow/stem-cell or solid organ transplantation.
  • Patients receiving autologous stem cell transplantation must wait 8 weeks before initiation of study drug administration.
  • Treatment with systemic chemotherapy or investigational therapy within 4 weeks of first study drug administration; other agents (e.g., biologics) within 2 weeks; radiation within 2 weeks; patients receiving 131I-MIBG therapy must wait 6 weeks prior to the initiation of study drug administration; corticosteroids (≥ 0.2 mg/kg/day prednisone or equivalent) or other immune suppressive drugs within the 2 weeks prior to the initiation of study drug administration.
  • History of clinically significant cardiovascular disease
  • Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug.
  • Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
  • Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction.
  • Second primary invasive malignancy that has not been in remission for greater than 2 years.
  • History of severe trauma or major surgery within 4 weeks prior to the initiation of study drug administration.
  • Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for enoblituzumab
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02982941


Contacts
Contact: Lisa Adali-Piston adalipistonl@macrogenics.com

Locations
United States, California
Lucile Packard Children's Hospital, Stanford Recruiting
Palo Alto, California, United States, 94304
Contact: Christin New    650-497-8815    newc@stanford.edu   
Principal Investigator: Crystal Mackall, MD         
United States, Maryland
National Cancer Institute, Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Melissa Amaya    240-760-6101    melissa.amaya@nih.gov   
Principal Investigator: Rosandra Kaplan, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maria Gemino-Borroemo    267-425-1987    geminoborm@email.chop.edu   
Principal Investigator: John M Maris, MD         
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Kathy McCarthy    832-824-4804    ksmccart@txch.org   
Principal Investigator: Meenakshi Hegde, MD         
United States, Washington
Seattle Children's Recruiting
Seattle, Washington, United States, 98105
Contact: Kimberly Starr    206-884-8163    kimberly.starr@seattlechildrens.org   
Principal Investigator: Julie Park, MD         
United States, Wisconsin
University of Wisconsin, American Family Children's Hospital Recruiting
Madison, Wisconsin, United States, 53792
Contact: Jenny Weiland    608-890-8070    jlweiland@pediatrics.wisc.edu   
Principal Investigator: Kenneth DeSantes, MD         
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: Sadhna Shankar, MD MacroGenics
  More Information

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02982941     History of Changes
Other Study ID Numbers: CP-MGA271-04
First Submitted: November 30, 2016
First Posted: December 6, 2016
Last Update Posted: September 19, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by MacroGenics:
Neuroblastoma
Rhabdomyosarcoma
Osteosarcoma
Ewing Sarcoma
Wilms Tumor
Desmoplastic Small Round Cell Tumor
pediatric

Additional relevant MeSH terms:
Neoplasms
Sarcoma
Neuroblastoma
Osteosarcoma
Rhabdomyosarcoma
Sarcoma, Ewing
Wilms Tumor
Desmoplastic Small Round Cell Tumor
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn