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NCT Number: NCT05642455

SPEARHEAD-3 Pediatric Study

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.

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Key information

Conditions

Synovial Sarcoma Fibrosarcoma Malignant Peripheral Nerve Sheath Tumor (MPNST) Neoplasms Neoplasms by Histologic Type Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Fibrous Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Nerve Sheath Neoplasms Nervous System Diseases Nervous System Neoplasms Neuroblastoma Neuroblastoma (NBL) Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Neurofibroma Neurofibrosarcoma Neuromuscular Diseases Osteosarcoma Peripheral Nervous System Diseases Peripheral Nervous System Neoplasms Sarcoma Sarcoma, Synovial

Age range

2 year–21 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Stanford University, Palo Alto, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Primary outcomes

  1. Incidence, duration, and severity of Treatment Emergent Adverse Events as assessed by Investigator Evaluation.

    Time frame: 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 outcomes

  1. 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)

    Time frame: 3.5 years

    ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017

  2. Time to response (TTR)

    Time frame: 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

  3. Duration of Response (DoR)

    Time frame: 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

  4. Best overall response (BOR)

    Time frame: 3.5 years

    BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for Neuroblastoma subjects)

  5. Progression Free Survival (PFS)

    Time frame: 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.

  6. Overall Survival (OS)

    Time frame: 15 years

    OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.

  7. Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence.

    Time frame: 3.5 years

    Obtain PBMC samples for the evaluation of peak persistence of afamitresgene autoleucel.

  8. Development and validation of an invitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval.

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

USWM CT, LLC

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2026
Study completion
2038
First posted
Dec 8, 2022
Registry last updated
Feb 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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