SPEARHEAD-3 Pediatric Study

NCT05642455 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ADP-0044-004
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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)

  3.5 years

Secondary Outcomes (8)

• 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

• Time to response (TTR)

  3.5 years

• Duration of Response (DoR)

  3.5 years

• Best overall response (BOR)

  3.5 years

• Progression Free Survival (PFS)

  3.5 years

Study Arms (1)

Afamitresgene autoleucel

EXPERIMENTAL

Genetic: Afamitresgene autoleucel

Interventions

Afamitresgene autoleucel GENETIC

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

Afamitresgene autoleucel

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• USWM CT, LLC: lead

Study Sites (10)

Stanford University

Palo Alto, California, 94305, United States

RECRUITING

National Institutes of Health

Bethesda, Maryland, 20892, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 10065, United States

NOT YET RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Kids

New York, New York, 10065, United States

NOT YET RECRUITING

Duke University School of Medicine

Durham, North Carolina, 27710, United States

NOT YET RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philedephia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

NOT YET RECRUITING

University of Wisconsin Cancer Center

Madison, Wisconsin, 53715, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma, Synovial; Neurofibrosarcoma; Neuroblastoma; Osteosarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Bone Tissue

Study Officials

• Fiorella Iglesias Cardenas, MD

  Memorial Sloan Kettering Kids

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: December 8, 2022
• Study Start: September 1, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): July 30, 2038
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (10)