Study of the Safety and Efficacy of Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb) in Patients With Relapsed/Refractory Neuroblastoma, Osteosarcoma and Other Solid Tumor Cancers

Inclusion Criteria:

Phase I

- Patients must have either (1) a diagnosis of NB as defined by international
criteria,i.e.,histopathology (confirmed by the MSKCC Department of Pathology) or BM
metastases plus high urine catecholamine levels, or (2) high grade osteosarcoma
verified by histopathology (confirmed by the MSKCC Department of Pathology), or (3)
other GD2-expressing solid tumor.

- For tumors other than NB and osteosarcoma, only tumors known to be GD2 positive are
eligible: melanoma, desmoplastic small round cell tumors, retinoblastoma,
medulloblastoma, and soft tissue sarcomas including liposarcoma, fibrosarcoma,
malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma. Patients
with medulloblastoma are eligible only if they have metastatic disease outside the CNS
(e.g. in the bone marrow)

- NB patients must have chemorefractory (e.g. refractory to standard induction
chemotherapy including cyclophosphamide, vincristine, cisplatin, etoposide) or
relapsed high-risk (HR) neuroblastoma. HR NB is defined as MYCN-amplified stage 3/4/4S
of any age, or MYCNnonamplified stage 4 in patients > 18 months of age at diagnosis.

- Osteosarcoma patients must have relapsed or refractory osteosarcoma after receiving
standard systemic chemotherapy (e.g. combination methotrexate, doxorubicin, and
cisplatin [MAP]).

- For non-NB and non-osteosarcoma tumors known to be GD2(+), patients must have relapsed
or refractory disease that is resistant to standard therapy.

Phase II

Group 1:

- NB patients must have chemo refractory or relapsed HR NB. HR NB is defined as
MYCNamplified stage 3/4/4S of any age, or MYCN-nonamplified stage 4 in patients > 18
months of age at diagnosis.

- The diagnosis of NB must be defined by international criteria i.e., histopathology
(confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine
catecholamine levels.

Group 2:

- Patients must have a diagnosis of high grade osteosarcoma defined by histopathology
(confirmed by the MSKCC Department of Pathology).

- Patients must have relapsed or refractory osteosarcoma after receiving standard
systemic chemotherapy (e.g. combination methotrexate, doxorubicin, and cisplatin
[MAP]).

All criteria below are common to both phase I and phase II:

Disease status

- For NB patients, patients must have measurable or evaluable disease (e.g. abnormal
findings in computed tomography (CT), magnetic resonance imaging (MRI),
metaiodobenzylguanidine (MIBG) scan, or positron emission tomography (PET)) OR
morphologic evidence of disease in bone marrow.

- For osteosarcoma or other GD2(+) solid tumor patients, patients must have measurable
disease.

Other criteria:

- Patients must be ≥ 1 year of age.

- Patients with prior exposure to anti-GD2 antibodies must have HAHA titer <1300U/ml.

- Adequate hematopoietic function defined as:

- Absolute neutrophil count ≥500/ul

- Absolute lymphocyte count ≥500/ul

- Platelet count ≥25,000/ul

- Negative serum pregnancy test in women of child-bearing potential.

- Women of child-bearing potential must be willing to practice an effective method of
birth control while on treatment.

- Signed informed consent indicating awareness of the investigational nature of this
program.

Exclusion Criteria:

- Patients who are in complete remission.

- Existing severe major organ dysfunction. i.e. renal, cardiac, hepatic, neurologic,
pulmonary, or gastrointestinal toxicity ≥ Grade 3 except for hearing loss, alopecia,
anorexia, nausea, hyperbilirubinemia or hypomagnesemia from TPN, which may be Grade 3.

- Hematologic and active CNS malignancies including CNS metastasis.

- Active life-threatening infection.

- Pregnant women or women who are breast-feeding.

- Inability to comply with protocol requirements.

- History of autoimmune disease with potential CNS involvement or a current autoimmune
disease.

- Chemotherapy or immunotherapy within three weeks prior to study enrollment. T-cell
based immunotherapies (e.g. CAR-modified T cells, checkpoint inhibitors) should have
been completed >6 weeks prior to treatment with hu3F8-BsAb.