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

NCT04044768 | Active Not Recruiting Phase 2 Results FDA Drug

• 1 other identifier: ADP 0044-002
• Study Type: interventional
• Target: 52
• Locations: 5 countries
• Sites: 26

Brief 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) .

Conditions

Synovial Sarcoma; Myxoid Liposarcoma

Keywords

Cell Therapy; T Cell Therapy; SPEAR T Cell; Sarcoma; MRCLS; MAGE A-4; Immuno-oncology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Adverse Events (AE) Including Serious Adverse Events (SAE), SAE, and Adverse Events of Special Interest (AESI) (Cohort 1)

  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)

  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)

  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)

  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)

  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.

Study Arms (1)

Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells

EXPERIMENTAL

Genetic: afamitresgene autoleucel (previously ADP-A2M4)

Interventions

afamitresgene autoleucel (previously ADP-A2M4) GENETIC

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

Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells

Eligibility Criteria

• Age: 10 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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

Sponsors & Collaborators

• USWM CT, LLC: lead

Study Sites (26)

City of Hope

Duarte, California, 91010, United States

Location

Stanford Cancer Center

Palo Alto, California, 94305, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Vanderbilt

Nashville, Tennessee, 37212, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutch

Seattle, Washington, 98109, United States

Location

Medical College of WI Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Leon Berard

Lyon, France

Location

Hospital Haut Leveque, CHU Bordeaux

Pessac, 33604, France

Location

Gustave Roussy Cancer Center

Villejuif, 94805, France

Location

Hospital Universitari Vall D'Hebron

Barcelona, Catalonia, 119-129, Spain

Location

Start Madrid-FJD, Fundación Jimѐnez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

UCLH Cancer Clinical Trials Unit

London, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 38554725 BACKGROUND

• 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.

  PMID: 32002290 DERIVED

MeSH Terms

Conditions

Sarcoma, Synovial; Liposarcoma, Myxoid; Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Liposarcoma; Neoplasms, Adipose Tissue

Results Point of Contact

• Title: Clinical Trials Management
• Organization: Adaptimmune

clinicaltrials@adaptimmune.com

+1 (215) 825 9260

Study Officials

• Dejka Araujo, MD

  MD Anderson Cancer Center; Houston TX 77030

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: August 5, 2019
• Study Start: August 13, 2019
• Primary Completion: August 29, 2021
• Study Completion (Estimated): April 1, 2038
• Last Updated: February 6, 2026
• Results First Posted: January 13, 2025

Record last verified: 2026-01

Locations

CA (1); ES (3); GB (2); FR (3); US (17)