SPEARHEAD-3 Pediatric Study

Neuroblastoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05642455
• Other study ID #: ADP-0044-004
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2023
• Est. completion date: July 30, 2038

Study information

• Verified date: April 2024
• Source: Adaptimmune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 30, 2038
• Est. primary completion date: October 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Malignant Peripheral Nerve Sheath Tumor (MPNST)
• Nerve Sheath Neoplasms
• Neuroblastoma
• Osteosarcoma
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

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

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	National Institue of Health	Bethesda	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University School of Medicine	Durham	North Carolina
United States	University of Wisconsin Cancer Center	Madison	Wisconsin
United States	Memorial Sloan Kettering Kids	New York	New York
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philedephia	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Adaptimmune

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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)	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 NB subjects)	ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017	3.5 years
Secondary	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	3.5 years
Secondary	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	3.5 years
Secondary	Best overall response (BOR)	BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for NB subjects)	3.5 years
Secondary	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 INCR, 2017 (for NB subjects) or death.	3.5 years
Secondary	Overall Survival (OS)	OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.	15 years
Secondary	Pharmacokinetics (PK). Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence.	Obtain PBMC samples for the evaluation of peak persistence of afamitresgene autoleucel.	3.5 years
Secondary	Development and validation of an invitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval.	Retention of additional tumor tissue during Pre-Screening to enable development and validation of the MAGE-A4 antigen expression companion diagnostic (CDx) assay.	3.5 years
Secondary	Invitro diagnostic (IVD) assay for screening	Development and validation of the MAGE-A4 antigen expression companion diagnostic assay	3.5 years