Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma (NBL), Osteosarcoma, Synovial Sarcoma
Conditions
Brief summary
This is a pediatric basket study to investigate the safety and efficacy of afamitresgene autoleucel in HLA-A\*02 eligible and MAGE-A4 positive subjects aged 2-17 years of age with advanced cancers.
Interventions
GENETICAfamitresgene autoleucel
Single infusion of afamitresgene autoleucel Dose: For subjects ≥10 kg to \<40 kg: starting dose of 0.025 - 0.200 x 10'9 transduced cells/kg. For subjects ≥40 kg 1.0x109 to 10x109 transduced by a single intravenous infusion
Sponsors
USWM CT, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma (SS), (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma (OS). * Age: (A) Synovial Sarcoma: 2 to 17 years (B) MPNST, Neuroblastoma and Osteosarcoma: 2 to 21 years * Body weight ≥ 10 kg * Must have previously received a systemic chemotherapy * Measurable disease prior to lymphodepletion according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only). * HLA-A\*02 positive * Tumor shows MAGE-A4 expression confirmed by central laboratory. * Performance Status: (A) Subjects ≥16: Eastern Cooperative Oncology Group (ECOG) 0 or 1 (B) Subjects 2 to 16: Lansky score ≥ 80 • Subject has anticipated life expectancy of greater than 3 months in the opinion of the investigator.
Exclusion criteria
* Positive for HLA-A\*02:05 in either allele; or any A\*02 having same protein sequence as HLA-A\*02:05 * History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide. * History of autoimmune or immune mediated disease * Known central nervous system (CNS) metastases. * Other prior malignancy that is not considered by the Investigator to be in complete remission * Clinically significant cardiovascular disease * Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus * Pregnant or breastfeeding * Experiencing ongoing rapid disease progression that in the opinion of the Investigator significantly increases the subjects risk associated with treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, duration, and severity of Treatment Emergent Adverse Events as assessed by Investigator Evaluation. | 3.5 years | Determination of incidence, severity and duration of adverse events * Incidence of dose limiting toxicities DLTs * AEs including serious adverse events (SAEs) * Incidence, severity, and duration of the AEs of special interest * Replication competent lentivirus (RCL) * T-cell clonality and insertional oncogenesis (IO) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Objective response rate (ORR) assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (or by International Neuroblastoma Response Criteria [INRC] 2017 in Neuroblastoma subjects) | 3.5 years | ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017 |
| Time to response (TTR) | 3.5 years | For patients who are observed to respond to afamitresgene autoleucel in the time from date of infusion to achieve a partial response or complete response (TTR) is assessed |
| Duration of Response (DoR) | 3.5 years | For patients who are observed to respond to afamitresgene autoleucel the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression |
| Best overall response (BOR) | 3.5 years | BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for Neuroblastoma subjects) |
| Progression Free Survival (PFS) | 3.5 years | PFS is assessed by the investigator from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death. |
| Overall Survival (OS) | 15 years | OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death. |
| Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence. | 3.5 years | Obtain PBMC samples for the evaluation of peak persistence of afamitresgene autoleucel. |
| Development and validation of an invitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval. | 3.5 years | Retention of additional tumor tissue during Pre-Screening to enable development and validation of a MAGE-A4 antigen expression companion diagnostic (CDx) assay. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFiorella Iglesias Cardenas, MD
Memorial Sloan Kettering Kids
Outcome results
None listed