Neuroblastoma, Osteosarcoma, Other Solid Tumor Cancers
Conditions
Keywords
Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb), 18-034
Brief summary
The purpose of this study is to test the safety of a study drug called humanized 3F8 bispecific antibody (Hu3F8-BsAb).
Interventions
BIOLOGICALHumanized 3F8 Bispecific Antibody
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.
OTHERBlood draw
In cycle 1, blood is drawn for PK studies.
Sponsors
Y-mAbs Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) Phase I | Days 1 through 28 in cycle 1 | Summary of DLTs in DLT evaluable subjects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.009 mcg/kg/Cycle Phase I Hu3F8-BsAb Dose level 1 (0.009 mcg/kg/cycle) is given IV over \
1-3 hours on Days 1 (0.0045 mcg/kg) and 8 (0.0045 mcg/kg) for each cycle. | 1 |
| 0.09 mcg/kg/Cycle Phase I Hu3F8-BsAb Dose level 2 (0.09 mcg/kg/cycle) is given IV over \
1-3 hours on Days 1 (0.045 mcg/kg) and 8 (0.45 mcg/kg) for each cycle. | 1 |
| 0.9 mcg/kg/Cycle Phase I Hu3F8-BsAb Dose level 3 (0.9 mcg/kg/cycle) is given IV over \
1-3 hours on Days 1 (0.45 mcg/kg) and 8 (0.45 mcg/kg) for each cycle. | 1 |
| 2.6 mcg/kg/Cycle Phase I Hu3F8-BsAb Dose level 4 (2.6 mcg/kg/cycle) is given IV over \
1-3 hours on Days 1 (1.3 mcg/kg) and 8 (1.3 mcg/kg) for each cycle. | 3 |
| 4.8 mcg/kg/Cycle Phase I Hu3F8-BsAb Dose level 5 (4.8 mcg/kg/cycle) is given IV over \
1-3 hours on Days 1 (1.3 mcg/kg) and 8 (3.5 mcg/kg) for each cycle. | 2 |
| 9.3 mcg/kg/Cycle Phase I Hu3F8-BsAb Dose level 6 (9.3 mcg/kg/cycle) is given IV over \
1-3 hours on Days 1 (1.3 mcg/kg) and 8 (8 mcg/kg) for each cycle. | 3 |
| Total | 11 |
Baseline characteristics
| Characteristic | 0.09 mcg/kg/Cycle | 0.9 mcg/kg/Cycle | 0.009 mcg/kg/Cycle | 2.6 mcg/kg/Cycle | 4.8 mcg/kg/Cycle | 9.3 mcg/kg/Cycle | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized 0- 6 years | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Customized 12-17 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized 18 years and above | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Age, Customized 7-11 years | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Disease Type High Grade Ostersarcoma | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Disease Type Neuroblastoma | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 9 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | 1 participants | 3 participants | 2 participants | 3 participants | 11 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 0 / 1 | 1 / 1 | 2 / 3 | 2 / 2 | 3 / 3 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 3 / 3 | 2 / 2 | 3 / 3 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 0 / 1 | 1 / 3 | 1 / 2 | 3 / 3 |
Outcome results
Primary
Dose Limiting Toxicities (DLTs) Phase I
Summary of DLTs in DLT evaluable subjects.
Time frame: Days 1 through 28 in cycle 1
Population: DLT Evaluable Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.009 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Nervous system disorder | 0 Participants |
| 0.009 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | Any DLT | 0 Participants |
| 0.009 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Syncope | 0 Participants |
| 0.09 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Nervous system disorder | 0 Participants |
| 0.09 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | Any DLT | 0 Participants |
| 0.09 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Syncope | 0 Participants |
| 0.9 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Nervous system disorder | 0 Participants |
| 0.9 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | Any DLT | 0 Participants |
| 0.9 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Syncope | 0 Participants |
| 2.6 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Nervous system disorder | 0 Participants |
| 2.6 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | Any DLT | 0 Participants |
| 2.6 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Syncope | 0 Participants |
| 4.8 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Nervous system disorder | 0 Participants |
| 4.8 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | Any DLT | 0 Participants |
| 4.8 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Syncope | 0 Participants |
| 9.3 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | Any DLT | 2 Participants |
| 9.3 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Syncope | 1 Participants |
| 9.3 mcg/kg/Cycle | Dose Limiting Toxicities (DLTs) Phase I | DLT Type - Nervous system disorder | 1 Participants |