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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT05642455Sponsor: USWM CT, LLCLast updated: 2026-02-09

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.

Arms & 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

Outcome measures

Primary

  • 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)

    Time frame: 3.5 years

Secondary

  • 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

  • Time to response (TTR)

    Time frame: 3.5 years

  • Duration of Response (DoR)

    Time frame: 3.5 years

  • Best overall response (BOR)

    Time frame: 3.5 years

  • Progression Free Survival (PFS)

    Time frame: 3.5 years

  • Overall Survival (OS)

    Time frame: 15 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

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

    Time frame: 3.5 years

Eligibility criteria

Sex: AllAge: 2 Years to 21 YearsHealthy volunteers: No
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 locations (10)

Stanford University

Palo Alto, California, 94305

Recruiting
Sneha Ramakrishna, MD · Principal Investigator

National Institutes of Health

Bethesda, Maryland, 20892

Recruiting
Kane Kaosaard · Contact
John Glod, MD · Principal Investigator

Dana Farber Cancer Institute

Boston, Massachusetts, 10065

Not Yet Recruiting
Natalie Collins, MD · Principal Investigator

Washington University

St Louis, Missouri, 63110

Recruiting
Tina Primeau, BA · Contact
Catie Knoerle, BA · Contact
Amy Armstrong, MD · Principal Investigator

Memorial Sloan Kettering Kids

New York, New York, 10065

Not Yet Recruiting
Fiorella Iglesias Cardenas, MD · Contact
Fiorella Iglesias Cardenas, MD · Principal Investigator

Duke University School of Medicine

Durham, North Carolina, 27710

Not Yet Recruiting
Kris Mahadeo, MD · Contact
Kris Mahadeo, MD · Principal Investigator

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

Recruiting
Brian Turpin, DO · Contact
Brian Turpin, DO · Principal Investigator

Children's Hospital of Philedephia

Philadelphia, Pennsylvania, 19104

Recruiting
Shelby Brizzolara-Dove, BS · Contact
Theodore Laetsch, MD · Principal Investigator

Seattle Children's Hospital

Seattle, Washington, 98105

Not Yet Recruiting
Mark Fluchel, MD · Principal Investigator

University of Wisconsin Cancer Center

Madison, Wisconsin, 53715

Recruiting
Christian Capitini, MD · Principal Investigator
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