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

Sponsor

MacroGenics (Industry)

Overall Status

Completed

CT.gov ID

NCT02982941

Collaborator

(none)

Enrollment

Locations

Arm

29.6

Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

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

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

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

Study Start Date :

Dec 1, 2016

Actual Primary Completion Date :

May 22, 2019

Actual Study Completion Date :

May 22, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Safety and tolerability of enoblituzumab. [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 of first dose through end of treatment (up to 96 weeks)]
PK of enoblituzumab
Number of participants that develop anti-drug antibodies [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 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lucile Packard Children's Hospital, Stanford	Palo Alto	California	United States	94304
2	National Cancer Institute, Center for Cancer Research	Bethesda	Maryland	United States	20892
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
4	Texas Children's Hospital	Houston	Texas	United States	77030
5	Seattle Children's	Seattle	Washington	United States	98105
6	University of Wisconsin, American Family Children's Hospital	Madison	Wisconsin	United States	53792