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

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of a study drug called humanized 3F8 bispecific antibody (Hu3F8-BsAb).

Official Title
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Phase I/II Study of Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb) in Patients With Relapsed/Refractory Neuroblastoma, Osteosarcoma, and Other GD2(+) Solid Tumors

Conditions
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Neuroblastoma, Osteosarcoma, Other Solid Tumor Cancers

Intervention / Treatment
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* Biological: Humanized 3F8 Bispecific Antibody
* Other: Blood draw


Participation Criteria
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Eligibility Criteria
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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 ( protocol amendment 1.0-5.0) Patients must be ≥ 1 year of age and < 18 years of age (protocol amendment 6.0-10.0) Patients with prior exposure to anti-GD2 antibodies must have a negative HAHA antibody titer 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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This phase I/II trial will assess the toxicity and pharmacokinetics (PK) of the humanized anti-GD2 x anti-CD3 bispecific antibody (hu3F8-BsAb) in phase I and the anti-tumor activity of hu3F8-BsAb in phase II.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hu3F8-BsAb<br>Phase I Hu3F8-BsAb is given IV over  1-3 hours on Days 1 and 8 for each cycle. In cycle 1, blood is drawn for PK studies.Phase II Hu3F8-BsAb is given IV over  1-3 hours on Days 1 and 8 for each cycle. | Biological: Humanized 3F8 Bispecific Antibody<br>* Phase I Hu3F8-BsAb is given IV over  1-3 hours on Days 1 and 8 for each cycle.Phase II Hu3F8-BsAb is given IV over  1-3 hours on Days 1 and 8 for each cycle.<br>* Other names: Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb);Other: Blood draw<br>* In cycle 1, blood is drawn for PK studies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLTs) Phase I | Summary of DLTs in DLT evaluable subjects. | Days 1 through 28 in cycle 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb), 18-034