Title
A Phase 1/2, Open-Label, Basket Study to Assess the Safety, Tolerability, and Anti-Tumor Activity of Afamitresgene Autoleucel in Pediatric Subjects with MAGE-A4 Positive Tumors

Description
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 2-21 years of age with advanced cancers

Objective
Primary: Incidence, duration, and severity of Treatment Emergent Adverse Events as assessed by Investigator Evaluation.
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:
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 NB subjects).
ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017
Time to response (TTR).
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).
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).
BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for NB subjects)
Progression Free Survival (PFS).
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 INCR, 2017 (for NB subjects) or death.
Overall Survival (OS).
OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.
Pharmacokinetics (PK). Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence.
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..
Retention of additional tumor tissue during Pre-Screening to enable development and validation of the MAGE-A4 antigen expression companion diagnostic (CDx) assay.
Invitro diagnostic (IVD) assay for screening.
Development and validation of the MAGE-A4 antigen expression companion diagnostic assay

Treatment Genetic: Afamitresgene autoleucel

Key Eligibility Inclusion Criteria:

Age 2-21 years
Body weight >/= 10 kg
Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
Must have previously received a systemic chemotherapy
Measurable disease 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: ECOG 0-1 or Lansky Score >/= 80

Applicable Disease Sites
Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Uterus

Participating Institutions
American Family Children's Hospital (AFCH); UW Health University Hospital