Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

Synovial Sarcoma Clinical Trial

Official title:

A Phase 2 Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR™ T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04044768
• Other study ID #: ADP 0044-002
• Status: Recruiting
• Phase: Phase 2
• Start date: August 13, 2019
• Est. completion date: April 1, 2038

Study information

• Verified date: February 2024
• Source: Adaptimmune
• Contact: Adaptimmune Patient Enquiries
• Phone: 215-825-9260
• Email: patients[@]adaptimmune.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study to investigate the efficacy and safety of ADP-A2M4 in HLA-A*02 eligible and MAGE-A4 positive subjects with metastatic or inoperable (advanced) Synovial Sarcoma (Cohort 1, 2 and 3 ) or MRCLS (Cohort 1) .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: April 1, 2038
• Est. primary completion date: October 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 75 Years

Eligibility

Key Inclusion Criteria

• Age =16 (10 years at selected sites) and <=75 years
• Diagnosis of advanced synovial sarcoma (Cohort 1, Cohort 2 and Cohort 3) or myxoid liposarcoma / myxoid round cell liposarcoma (Cohort 1 only) confirmed by cytogenetics.
• Previously received either an anthracycline or ifosfamide containing regimen.
• Measurable disease according to RECIST v1.1 prior to lymphodepletion
• HLA-A*02:01, HLA-A*02:02, HLA-A*02:03 or HLA-A*02:06 positive
• Tumor shows MAGE-A4 expression confirmed by central laboratory. North America Only (United States and Canada): Tumor (either an archival specimen or a fresh biopsy) shows MAGE-A4 expression of =1+ staining in =10% of the cells by immunohistochemistry.
• ECOG Performance Status of 0 or1. For subjects aged =10 to =16 years old:

Lansky Score =60%.

• Left ventricular ejection fraction (LVEF) =50%. Note: other protocol defined Inclusion criteria may apply

Key Exclusion Criteria:

• HLA-A*02:05 in either allele
• Received or plans to receive the following therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy: Cytotoxic chemotherapy, Tyrosine kinase inhibitor (TKI) (e.g. pazopanib), Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors,), Anti-cancer Vaccine, Gene therapy using an integrating vector (subjects who have received a gene therapy using a lentiviral vector may be eligible for the study), Corticosteroids or any other immunosuppressive therapy, Investigational treatment or interventional clinical trial, Allogeneic hematopoietic stem cell transplant, Radiotherapy to the target lesions, Major surgery
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
• History of autoimmune or immune mediated disease
• Symptomatic CNS metastases including leptomeningeal disease.
• Other prior malignancy that is not considered by the Investigator to be in complete remission
• Clinically significant cardiovascular disease
• Uncontrolled intercurrent illness
• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
• Pregnant or breastfeeding Note: other protocol defined Exclusion criteria may apply.

Related Conditions & MeSH terms

• Liposarcoma
• Liposarcoma, Myxoid
• Myxoid Liposarcoma
• Sarcoma
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

Genetic:
• afamitresgene autoleucel (previously ADP-A2M4)
Single infusion of autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) Dose: 1.0 x109 to 10x109 transduced by a single intravenous infusion

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	Centre Leon Berard	Lyon
France	Hospital Haut Leveque, CHU Bordeaux	Pessac
France	Gustave Roussy Cancer Center	Villejuif
Spain	Hospital Universitari Vall D'Hebron	Barcelona	Cataluna
Spain	Start Madrid-FJD, Fundación Jim?nez Díaz	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	UCLH Cancer Clinical Trials Unit	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	National Cancer Institute	Bethesda	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Medical College of WI Froedtert Hospital	Milwaukee	Wisconsin
United States	Vanderbilt	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Stanford Cancer Center	Palo Alto	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Fred Hutch	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Adaptimmune

Countries where clinical trial is conducted

United States,  Canada,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Overall Response Rate (ORR)	ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1	2.5 years
Secondary	Number of subjects with treatment -related adverse events (AEs), including serious adverse events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs)	2.5 years
Secondary	Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells	Evaluation of RCL using PCR -based assay in peripheral blood.	15 years
Secondary	Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs).	Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs )	2.5 years
Secondary	Efficacy: Best overall response (BOR)	BOR is per RECIST V1.1.	2.5 years
Secondary	Time to response (TTR)	For patients who are observed to respond to ADP-A2M4, the time taken from date of infusion to achieve a partial response or complete response (TTR) is assessed.	2.5 years
Secondary	Duration of Response (DoR)	For patients who are observed to respond to ADP-A2M4, the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression per RECIST v 1.1 or death.	2.5 years
Secondary	Progression Free Survival (PFS)	PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death.	2.5 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	Quantitation of genetically engineered T-cells in PBMCs	Quantitation of genetically engineered T-cells in PBMCs by qPCR	2.5 years
Secondary	Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs	Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry	2.5 years
Secondary	Quantitation of genetically engineered T-cells in PBMCs	Quantitation of genetically engineered T-cells in PBMCs by flow cytometry	2.5 years
Secondary	Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs	Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR	2.5 years
Secondary	In vitro diagnostic (IVD) assay for screening	Development and validation of the MAGE-A4 antigen expression companion diagnostic assay	2.5 years