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

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: Active, not recruiting
• Conditions: Myxoid Liposarcoma; Synovial Sarcoma
• Intervention / Treatment: Genetic: afamitresgene autoleucel (previously ADP-A2M4)

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• France
  • Lyon, France
    • Centre Léon Bérard
  • Pessac, France, 33604
    • Hospital Haut Leveque, CHU Bordeaux
  • Villejuif, France, 94805
    • Gustave Roussy Cancer Center
• Spain
  • Madrid, Spain, 28040
    • Start Madrid-FJD, Fundación Jimѐnez Díaz
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Catalonia
    • Barcelona, Catalonia, Spain, 119-129
      • Hospital Universitari Vall d'Hebron
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • UCLH Cancer Clinical Trials Unit
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Jacksonville, Florida, United States, 33612
      • Mayo Clinic Jacksonville
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Robert H. Lurie Comprehensive Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of WI Froedtert Hospital

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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
Overall Response Rate (ORR) (Cohort 1)	Percentage of participants with confirmed tumor response (complete [CR] or partial [PR] response) to treatment as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Independent Radiologist review (Cohort 1)	From T-cell infusion until disease progression/recurrence as of data cut off (up to 2 years). Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE) Including Serious Adverse Events (SAE), SAE, and Adverse Events of Special Interest (AESI) (Cohort 1)	An AE was defined as any untoward medical occurrence in a subject or clinical study participant temporally associated with the use of the study intervention, whether or not considered related to the study intervention. Therefore, an AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants with AEs (including SAE), SAE and AESI including cytokine release syndrome, neurotoxicity, ICANS, prolonged cytopenia are presented.	AEs, SAEs, and AESIs were collected at each visit from the start of lymphodepletion of the first subject until the last subject discontinued the interventional phase in cohort 1 as of the safety cut off (up to 3.2 years).
The Number of Participants With Replication Competent Lentivirus (RCL)	The presence of RCL was assessed by qPCR targeting a segment of the vesicular stomatitis virus glycoprotein (VSV G) coding sequence.	From T-cell infusion to months 3, 6, and 12 post-infusion, then annually post-infusion (up to 2.8 years as of the data cut off).
Insertional Oncogenesis (IO)	Deoxyribonucleic acid (DNA) from participants peripheral blood mononuclear cell (PBMC) samples was subjected to lentiviral vector integration site analysis by next-generation sequencing, thus evaluating both the clonality status of the transduced cell population and the genomic localization of individual integration sites. The count of participants with integration sites representing more than 5% of all unique sites is presented.	From 10 months post T-cell infusion up to 20 months post T-cell infusion (as of the data cut off)
Best Overall Response (BOR) (Cohort 1)	BOR is the best response recorded from the start of T-cell infusion until disease progression/recurrence as assessed by Independent Radiologist review. Response categories are confirmed CR, confirmed PR, stable disease and confirmed progressive disease (PD). Best overall response is a stable disease, if CR or PR are unconfirmed.	From T-cell infusion until disease progression/recurrence as of data cut off (up to 2.6 years). Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.
Time to Response (TTR) (Cohort 1)	TTR was defined as the interval (weeks) from the date of T-cell infusion to the earliest date of the first documented confirmed CR or confirmed PR as assessed by Independent Radiologist review. TTR (in weeks) = [date of initial confirmed CR or PR - date of T-cell infusion + 1]/7.	From T-cell infusion until first documented confirmed CR or confirmed PR. Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.
Duration of Response (DoR) (Cohort 1)	DoR (in months) is defined as ((date of PD (or censoring) - date of initial confirmed CR/PR + 1)/365.25)*12 as assessed by Independent Radiologist review. Outcome Measure not yet reached as participants are ongoing in study	From initial confirmed response (CR or PR) until PD (or censored date) as of data cut off.
Progression Free Survival (PFS) (Cohort 1)	PFS is defined as the time from T-cell infusion to the date of the first documentation of PD or death due to any cause, whichever occurs first, as assessed by Independent Radiologist review. PFS (in weeks) was calculated as (date of PD/death [or censored date] - first T-cell infusion date + 1)/7.	From T-cell infusion until first documented PD or death due to any cause (or censored date), whichever occurs first, as of data cut off (up to 2.6 years). Response was assessed at Week 4, 8,12,16, 24, and every 2 months until confirmed PD
Overall Survival (OS) (Cohort 1)	OS is defined as the time from the date of T-cell infusion to the date of death (due to any reason) or censored date. OS in months was calculated as ((death date - first T-cell infusion date + 1)/365.25)*12. Outcome Measure not yet reached as participants are ongoing in study	From T-cell infusion to death due to any reason (or censored date) as of data cut off (up to 2.6 years).
Peak Persistence (Cohort 1)	Peak persistence of afamitresgene autoleucel cells was reported as vector copy numbers per microgram of genomic DNA from peripheral blood mononuclear cell (PBMC).	From T-cell infusion to 3.2 years (as of data cut off).
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
Quantitation of Genetically Engineered T-cells in PBMCs	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 taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR	2.5 years
In Vitro Diagnostic (IVD) Assay for Screening	Development and validation of the MAGE-A4 antigen expression companion diagnostic assay	2.5 years

Collaborators and Investigators

• Sponsor: USWM CT, LLC
• Investigators: Principal Investigator: Dejka Araujo, MD, MD Anderson Cancer Center; Houston TX 77030

Publications and helpful links

General Publications

• Sanderson JP, Crowley DJ, Wiedermann GE, Quinn LL, Crossland KL, Tunbridge HM, Cornforth TV, Barnes CS, Ahmed T, Howe K, Saini M, Abbott RJ, Anderson VE, Tavano B, Maroto M, Gerry AB. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology. 2019 Nov 24;9(1):1682381. doi: 10.1080/2162402X.2019.1682381. eCollection 2020.
• D'Angelo SP, Araujo DM, Abdul Razak AR, Agulnik M, Attia S, Blay JY, Carrasco Garcia I, Charlson JA, Choy E, Demetri GD, Druta M, Forcade E, Ganjoo KN, Glod J, Keedy VL, Le Cesne A, Liebner DA, Moreno V, Pollack SM, Schuetze SM, Schwartz GK, Strauss SJ, Tap WD, Thistlethwaite F, Valverde Morales CM, Wagner MJ, Wilky BA, McAlpine C, Hudson L, Navenot JM, Wang T, Bai J, Rafail S, Wang R, Sun A, Fernandes L, Van Winkle E, Elefant E, Lunt C, Norry E, Williams D, Biswas S, Van Tine BA. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. Lancet. 2024 Apr 13;403(10435):1460-1471. doi: 10.1016/S0140-6736(24)00319-2. Epub 2024 Mar 27.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2019
• Primary Completion (Actual): August 29, 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 6, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Sarcoma; Immuno-oncology; T Cell Therapy; SPEAR T Cell; MRCLS; MAGE A-4
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Liposarcoma; Sarcoma; Sarcoma, Synovial; Liposarcoma, Myxoid
• 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