RecruitingPhase 1Phase 2NCT05642455

SPEARHEAD-3 Pediatric Study

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

Sponsor

USWM CT, LLC

Enrollment

20 participants

Start Date

Sep 1, 2023

Study Type

INTERVENTIONAL

Conditions

Osteosarcoma Synovial Sarcoma Malignant Peripheral Nerve Sheath Tumor (MPNST)Neuroblastoma (NBL)

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.

Eligibility

Min Age: 2 YearsMax Age: 21 Years

Inclusion Criteria11

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 Criteria9

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.

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