SPEARHEAD-3 Pediatric Study

Phase 2RecruitingNCT05642455

USWM CT, LLC20 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

Afamitresgene autoleucelGENETIC

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

Eligibility

Sex: ALLMin age: 2 YearsMax age: 21 Years

Medical Language ↔ Plain English

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.

Locations (10)

Stanford University

Palo Alto, California, United States

RECRUITING

National Institutes of Health

Bethesda, Maryland, United States

RECRUITING

Outcomes

Primary Outcomes

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 Outcomes

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)

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

Time frame: 3.5 years

Time to response (TTR)

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

Time frame: 3.5 years

Duration of Response (DoR)

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

Time frame: 3.5 years

Best overall response (BOR)

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

Time frame: 3.5 years

Progression Free Survival (PFS)

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.