SPEARHEAD-3 Pediatric Study

February 5, 2026 updated by: USWM CT, LLC

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Recruiting
        • Stanford University
        • Principal Investigator:
          • Sneha Ramakrishna, MD
        • Contact:
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health
        • Principal Investigator:
          • John Glod, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 10065
        • Not yet recruiting
        • Dana Farber Cancer Institute
        • Principal Investigator:
          • Natalie Collins, MD
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Principal Investigator:
          • Amy Armstrong, MD
        • Contact:
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Memorial Sloan Kettering Kids
        • Contact:
        • Principal Investigator:
          • Fiorella Iglesias Cardenas, MD
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Not yet recruiting
        • Duke University School of Medicine
        • Principal Investigator:
          • Kris Mahadeo, MD
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Principal Investigator:
          • Brian Turpin, DO
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philedephia
        • Principal Investigator:
          • Theodore Laetsch, MD
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98105
        • Not yet recruiting
        • Seattle Children's Hospital
        • Principal Investigator:
          • Mark Fluchel, MD
    • Wisconsin
      • Madison, Wisconsin, United States, 53715
        • Recruiting
        • University of Wisconsin Cancer Center
        • Principal Investigator:
          • Christian Capitini, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Afamitresgene autoleucel
Genetic: Afamitresgene 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
3.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3.5 years
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
3.5 years
Overall Survival (OS)
Time Frame: 15 years
OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.
15 years
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
3.5 years
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)
3.5 years
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.
3.5 years
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.
3.5 years
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.
3.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

USWM CT, LLC

Investigators

  • Principal Investigator: Fiorella Iglesias Cardenas, MD, Memorial Sloan Kettering Kids

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2023

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

July 30, 2038

Study Registration Dates

First Submitted

November 7, 2022

First Submitted That Met QC Criteria

December 6, 2022

First Posted (Actual)

December 8, 2022

Study Record Updates

Last Update Posted (Actual)

February 9, 2026

Last Update Submitted That Met QC Criteria

February 5, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADP-0044-004

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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