Enoblituzumab (MGA271) in Children With B7-H3-expressing 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.

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.

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.