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

NCT02982941 | Completed Phase 1

• 1 other identifier: CP-MGA271-04
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Neuroblastoma; Rhabdomyosarcoma; Osteosarcoma; Ewing Sarcoma; Wilms Tumor; Desmoplastic Small Round Cell Tumor

Keywords

Neuroblastoma; Rhabdomyosarcoma; Osteosarcoma; Ewing Sarcoma; Wilms Tumor; Desmoplastic Small Round Cell Tumor; pediatric

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of enoblituzumab.

  Adverse events, SAEs, incidence of treatment-emergent AE

  Time of first dose through end of treatment (up to 2 years)

Secondary Outcomes (3)

• Peak plasma concentration

  Time of first dose through end of treatment (up to 96 weeks)

• Number of participants that develop anti-drug antibodies

  Time of first dose through end of treatment (up to 96 weeks)

• Antitumor activity of enoblituzumab

  Time of first dose through end of treatment (up to 96 weeks)

Study Arms (1)

Dose Escalation & Cohort Expansion

EXPERIMENTAL

enoblituzumab administered IV weekly

Drug: Enoblituzumab

Interventions

Enoblituzumab DRUG

enoblituzumab administered IV weekly for up to 96 weeks

Also known as: MGA271

Dose Escalation & Cohort Expansion

Eligibility Criteria

• Age: 1 Year - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age at treatment 1 to 35 years.
• 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 or malignant solid tumors of any other histology that test positive for B7-H3 .
• 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.

You may not qualify if:

• 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
• Patients in Canada may not have a history or evidence of latent or active tuberculosis infection.

Sponsors & Collaborators

• MacroGenics: lead

Study Sites (6)

Lucile Packard Children's Hospital, Stanford

Palo Alto, California, 94304, United States

Location

National Cancer Institute, Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's

Seattle, Washington, 98105, United States

Location

University of Wisconsin, American Family Children's Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Rhabdomyosarcoma; Osteosarcoma; Sarcoma, Ewing; Wilms Tumor; Desmoplastic Small Round Cell Tumor

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Chief Medical Officer

  MacroGenics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 6, 2016
• Study Start: December 1, 2016
• Primary Completion: May 22, 2019
• Study Completion: May 22, 2019
• Last Updated: February 8, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)