SPEARHEAD-3 Pediatric Study

Phase 1

Recruiting

• Conditions: Synovial Sarcoma; Malignant Peripheral Nerve Sheath Tumor (MPNST); Neuroblastoma; Osteosarcoma
• Interventions: Genetic: Afamitresgene autoleucel

• Registration Number: NCT05642455
• Lead Sponsor: Adaptimmune

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 2-21 years of age with advanced cancers

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-12-06
• Study First Posted: 2022-12-08
• Study Start: 2023-09-01
• Status Verified: 2024-04
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-26
• Primary Completion: 2026-10-01
• Study Completion: 2038-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Afamitresgene autoleucel	Afamitresgene autoleucel	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 the MAGE-A4 antigen expression companion diagnostic (CDx) assay.
Best overall response (BOR)	3.5 years	BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for NB subjects)
Pharmacokinetics (PK). 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.
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
Invitro diagnostic (IVD) assay for screening	3.5 years	Development and validation of the MAGE-A4 antigen expression companion diagnostic assay
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)	3.5 years	ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017
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
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 INCR, 2017 (for NB subjects) or death.
Overall Survival (OS)	15 years	OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.

Trial Locations

Locations (11)

National Institutes of Health; 🇺🇸 Bethesda, Maryland, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Memorial Sloan Kettering Kids; 🇺🇸 New York, New York, United States

Duke University School of Medicine; 🇺🇸 Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Children's Hospital of Philedephia; 🇺🇸 Philadelphia, Pennsylvania, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

University of Wisconsin Cancer Center; 🇺🇸 Madison, Wisconsin, United States