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

February 16, 2024 updated by: Adaptimmune

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

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) .

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Cancer Centre
        • Principal Investigator:
          • Albiruni G Razak, MD
        • Contact:
        • Contact:
  • France
      • Lyon, France
        • Recruiting
        • Centre Léon Bérard
        • Contact:
        • Principal Investigator:
          • Jean-Yves BLAY, MD
      • Pessac, France, 33604
        • Recruiting
        • Hospital Haut Leveque, CHU Bordeaux
        • Contact:
        • Principal Investigator:
          • Edouard Forcade, MD
      • Villejuif, France, 94805
        • Recruiting
        • Gustave Roussy Cancer Center
        • Contact:
        • Principal Investigator:
          • Axel Le Cesne, MD
  • Spain
      • Madrid, Spain, 28040
      • Sevilla, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen Del Rocio
        • Contact:
        • Contact:
        • Principal Investigator:
          • Irene Carrasco Garcia, MD
    • Cataluna
      • Barcelona, Cataluna, Spain, 119-129
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Principal Investigator:
          • Claudia Valverde, MD
        • Contact:
  • United Kingdom
      • London, United Kingdom, NW1 2PG
        • Recruiting
        • UCLH Cancer Clinical Trials Unit
        • Principal Investigator:
          • Sandra Strauss, MD
        • Contact:
        • Contact:
      • Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie NHS Foundation Trust
        • Principal Investigator:
          • Fiona Thistlethwaite, MD
        • Contact:
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Principal Investigator:
          • Mark Agulnik, MD
        • Contact:
        • Contact:
      • Palo Alto, California, United States, 94305
        • Recruiting
        • Stanford Cancer Center
        • Principal Investigator:
          • Kristen Ganjoo, MD
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado
        • Principal Investigator:
          • Breelyn Wilky, MD
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 33612
        • Recruiting
        • Mayo Clinic Jacksonville
        • Principal Investigator:
          • Steven Attia, MD
        • Contact:
      • Tampa, Florida, United States, 33612
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University Robert H. Lurie Comprehensive Cancer Center
        • Principal Investigator:
          • Seth Pollack, MD
        • Contact:
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Cancer Institute
        • Principal Investigator:
          • John Glod, MD
        • Contact:
    • Massachusetts
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Principal Investigator:
          • Scott Schuetze
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Brian Van Tine, M.D.
        • Contact:
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
        • Contact:
        • Principal Investigator:
          • Sandra D'Angelo, MD
      • New York, New York, United States, 10032
        • Withdrawn
        • Columbia University
    • Ohio
      • Columbus, Ohio, United States, 43210
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Recruiting
        • Vanderbilt
        • Principal Investigator:
          • Vicki Keedy, MD
        • Contact:
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Dejka Araujo, MD
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutch
        • Principal Investigator:
          • Elizabeth Loggers, MD
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of WI Froedtert Hospital
        • Principal Investigator:
          • John Charlson
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy: Overall Response Rate (ORR)
Time Frame: 2.5 years
ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1
2.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs).
Time Frame: 2.5 years
Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs )
2.5 years
Efficacy: Best overall response (BOR)
Time Frame: 2.5 years
BOR is per RECIST V1.1.
2.5 years
Time to response (TTR)
Time Frame: 2.5 years
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
Duration of Response (DoR)
Time Frame: 2.5 years
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
Progression Free Survival (PFS)
Time Frame: 2.5 years
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
Overall Survival (OS)
Time Frame: 15 years
OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death
15 years
Quantitation of genetically engineered T-cells in PBMCs
Time Frame: 2.5 years
Quantitation of genetically engineered T-cells in PBMCs by qPCR
2.5 years
Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs
Time Frame: 2.5 years
Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry
2.5 years
Quantitation of genetically engineered T-cells in PBMCs
Time Frame: 2.5 years
Quantitation of genetically engineered T-cells in PBMCs by flow cytometry
2.5 years
Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs
Time Frame: 2.5 years
Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR
2.5 years
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
Time Frame: 2.5 years
Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs)
2.5 years
Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells
Time Frame: 15 years
Evaluation of RCL using PCR -based assay in peripheral blood.
15 years
In vitro diagnostic (IVD) assay for screening
Time Frame: 2.5 years
Development and validation of the MAGE-A4 antigen expression companion diagnostic assay
2.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Adaptimmune

Investigators

  • Principal Investigator: Dejka Araujo, MD, MD Anderson Cancer Center; Houston TX 77030

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 13, 2019

Primary Completion (Actual)

October 10, 2021

Study Completion (Estimated)

April 1, 2038

Study Registration Dates

First Submitted

July 9, 2019

First Submitted That Met QC Criteria

August 1, 2019

First Posted (Actual)

August 5, 2019

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 16, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADP 0044-002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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