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

A Phase 1, Open-label, Dose Escalation Study of MGA271 in Pediatric Patients With B7-H3-Expressing Relapsed or Refractory Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Osteosarcoma; Ewing Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Wilms Tumor; Desmoplastic Small Round Cell Tumor
• Intervention / Treatment: Drug: Enoblituzumab

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, desmoplastic small round cell tumors, or malignant solid tumors of any other histology that test positive for B7-H3.

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital, Stanford
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute, Center for Cancer Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin, American Family Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

General Inclusion Criteria:

• 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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation & Cohort Expansion; enoblituzumab administered IV weekly	Drug: Enoblituzumab; enoblituzumab administered IV weekly for up to 96 weeks; Other Names: MGA271

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration	PK of enoblituzumab	Time of first dose through end of treatment (up to 96 weeks)
Number of participants that develop anti-drug antibodies	Proportion of patients who develop anti-MGA271 antibodies, immunogenicity	Time of first dose through end of treatment (up to 96 weeks)
Antitumor activity of enoblituzumab	Anti-tumor activity of enoblituzumab using conventional RECIST 1.1 and immune related RECIST criteria	Time of first dose through end of treatment (up to 96 weeks)

Collaborators and Investigators

• Sponsor: MacroGenics

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): May 22, 2019

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: pediatric; Ewing Sarcoma; Rhabdomyosarcoma; Osteosarcoma; Neuroblastoma; Desmoplastic Small Round Cell Tumor; Wilms Tumor
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Neoplasms, Glandular and Epithelial; Genetic Diseases, Inborn; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Neoplasms, Complex and Mixed; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive; Neoplasms, Muscle Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Myosarcoma; Neoplasms; Sarcoma; Sarcoma, Ewing; Osteosarcoma; Neuroblastoma; Rhabdomyosarcoma; Wilms Tumor; Desmoplastic Small Round Cell Tumor
• Other Study ID Numbers: CP-MGA271-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No