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

August 31, 2023 updated by: Y-mAbs Therapeutics

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

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

Study Overview

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 17 years (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hu3F8-BsAb
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.
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.
Other Names:
  • Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb)
In cycle 1, blood is drawn for PK studies.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2019

Primary Completion (Actual)

October 20, 2021

Study Completion (Actual)

October 20, 2021

Study Registration Dates

First Submitted

February 28, 2019

First Submitted That Met QC Criteria

February 28, 2019

First Posted (Actual)

March 1, 2019

Study Record Updates

Last Update Posted (Actual)

September 13, 2023

Last Update Submitted That Met QC Criteria

August 31, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

IPD Plan Description

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

IPD Sharing Supporting Information Type

  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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