Clinical trial NCT03860207: 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
Official title: Phase I/II Study of Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb) in Patients With Relapsed/Refractory Neuroblastoma, Osteosarcoma, and Other GD2(+) Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Neuroblastoma
Osteosarcoma
Other Solid Tumor Cancers
Keywords: Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb)
18-034
Lead sponsor: Y-mAbs Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-03-01
Enrollment: 12
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs) Phase I
timeFrame: Days 1 through 28 in cycle 1
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
References:
citation: Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.