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

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

Sponsors

Lead Sponsor: Memorial Sloan Kettering Cancer Center

Source Memorial Sloan Kettering Cancer Center
Brief Summary

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

Overall Status Recruiting
Start Date February 22, 2019
Completion Date February 2022
Primary Completion Date February 2022
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
maximum tolerated dosage (MTD) Phase I Days 1 through 28
Enrollment 30
Condition
Intervention

Intervention Type: Biological

Intervention Name: Humanized 3F8 Bispecific Antibody

Description: 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.

Arm Group Label: Hu3F8-BsAb

Other Name: Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb)

Intervention Type: Other

Intervention Name: Blood draw

Description: In cycle 1, blood is drawn for PK studies.

Arm Group Label: 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.

- 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.

Gender: All

Minimum Age: 2 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Shakeel Modak, MD Principal Investigator Memorial Sloan Kettering Cancer Center
Overall Contact

Last Name: Shakeel Modak, MD

Phone: 212-639-7623

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: Memorial Sloan Kettering Cancer Center Shakeel Modak, MD 212-639-7623 Shakeel Modak Principal Investigator
Location Countries

United States

Verification Date

November 2019

Responsible Party

Type: Sponsor

Keywords
Condition Browse
Number Of Arms 1
Arm Group

Label: Hu3F8-BsAb

Type: Experimental

Description: 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.

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

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

Masking: None (Open Label)

Source: ClinicalTrials.gov