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

NCT03860207 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 18-034
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Neuroblastoma; Osteosarcoma; Other Solid Tumor Cancers

Keywords

Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb); 18-034

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (DLTs) Phase I

  Summary of DLTs in DLT evaluable subjects.

  Days 1 through 28 in cycle 1

Study Arms (1)

Hu3F8-BsAb

EXPERIMENTAL

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; Other: Blood draw

Interventions

Humanized 3F8 Bispecific Antibody BIOLOGICAL

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.

Also known as: Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb)

Hu3F8-BsAb

Blood draw OTHER

In cycle 1, blood is drawn for PK studies.

Hu3F8-BsAb

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 31401903 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The study was terminated after 11 subjects due to a business strategy decision. At this point the maximum tolerated dose was not established.

Results Point of Contact

• Title: Joris Wilms
• Organization: Y-mAbs Therapeutics

clinicaltrials@ymabs.com

+45 7026 1414

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 1, 2019
• Study Start: February 22, 2019
• Primary Completion: October 20, 2021
• Study Completion: October 20, 2021
• Last Updated: September 13, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-08

Locations

US (1)