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

• Status: Completed
• Trial end date: 2019-05-22
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MacroGenics

Criteria

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.