Clinical trial NCT05642455: SPEARHEAD-3 Pediatric Study
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Synovial Sarcoma
Malignant Peripheral Nerve Sheath Tumor (MPNST)
Neuroblastoma
Osteosarcoma
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2022-12-08
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 2-21 years of age with advanced cancers


Eligibility criteria: Inclusion Criteria:

* Age 2-21 years
* Body weight ≥ 10 kg
* Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
* Must have previously received a systemic chemotherapy
* Measurable disease 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: ECOG 0-1 or Lansky Score ≥ 80

Exclusion Criteria:

* 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

Primary outcomes:
measure: Incidence, duration, and severity of Treatment Emergent Adverse Events as assessed by Investigator Evaluation.
timeFrame: 3.5 years
Secondary outcomes:
measure: 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 NB subjects)
timeFrame: 3.5 years
measure: Time to response (TTR)
timeFrame: 3.5 years
measure: Duration of Response (DoR)
timeFrame: 3.5 years
measure: Best overall response (BOR)
timeFrame: 3.5 years
measure: Progression Free Survival (PFS)
timeFrame: 3.5 years
measure: Overall Survival (OS)
timeFrame: 15 years
measure: Pharmacokinetics (PK). Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence.
timeFrame: 3.5 years
measure: Development and validation of an invitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval.
timeFrame: 3.5 years
measure: Invitro diagnostic (IVD) assay for screening
timeFrame: 3.5 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Kids
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philedephia
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Memorial Sloan Kettering Kids
name: Fiorella Iglesias Cardenas, MD
role: PRINCIPAL_INVESTIGATOR
References: