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Synovial SarcomaPhase 2NCT04044768

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

A Phase 2 study testing afamitresgene autoleucel (previously ADP-A2M4) in people with Synovial Sarcoma and Myxoid Liposarcoma, run by USWM CT, LLC at 26 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

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) . Read more about this study

Who is it for?
Ages 10 to 75 years
Conditions the study is for
Synovial Sarcoma, Myxoid Liposarcoma
What is being tested?
afamitresgene autoleucel (previously ADP-A2M4)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
26 sitesin 5 countries
Study dates
13 Aug 2019to 1 Apr 2038
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

26 sites in 5 countries.

26 sites in 5 countries

United States17 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Colorado

    Aurora, Colorado, 80045

  • National Cancer Institute

    Bethesda, Maryland, 20892

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern University Robert H. Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • Ohio State University

    Columbus, Ohio, 43210

  • City of Hope

    Duarte, California, 91010

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 33612

  • Medical College of WI Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Vanderbilt

    Nashville, Tennessee, 37212

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Stanford Cancer Center

    Palo Alto, California, 94305

  • Fred Hutch

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

France3 sites

  • Centre Leon Berard

    Lyon

  • Hospital Haut Leveque, CHU Bordeaux

    Pessac, 33604

  • Gustave Roussy Cancer Center

    Villejuif, 94805

Other trials in France

Spain3 sites

  • Hospital Universitari Vall D'Hebron

    Barcelona, Catalonia, 119-129

  • Start Madrid-FJD, Fundación Jimѐnez Díaz

    Madrid, 28040

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

Other trials in Spain

United Kingdom2 sites

  • UCLH Cancer Clinical Trials Unit

    London, NW1 2PG

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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

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) .

Being tested
afamitresgene autoleucel (previously ADP-A2M4)
Keywords
Cell Therapy, T Cell Therapy, SPEAR T Cell, Sarcoma, MRCLS, MAGE A-4, Immuno-oncology
Medical subject headings
Sarcoma, Synovial, Liposarcoma, Myxoid, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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

Study groups in NCT04044768
Study groupRoleWhat they receive
Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cellsExperimentalNot described
Receives: Genetic: afamitresgene autoleucel (previously ADP-A2M4)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 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)

  1. 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.

    Measured: 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).

  2. 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.

    Measured: 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).

  3. 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.

    Measured: From 10 months post T-cell infusion up to 20 months post T-cell infusion (as of the data cut off)

  4. 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.

    Measured: 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.

  5. 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.

    Measured: 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.

  6. 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

    Measured: From initial confirmed response (CR or PR) until PD (or censored date) as of data cut off.

  7. 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.

    Measured: 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

  8. 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

    Measured: From T-cell infusion to death due to any reason (or censored date) as of data cut off (up to 2.6 years).

  9. 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).

    Measured: From T-cell infusion to 3.2 years (as of data cut off).

  10. 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

    Measured: 2.5 years

  11. Quantitation of Genetically Engineered T-cells in PBMCs

    Quantitation of genetically engineered T-cells in PBMCs by flow cytometry

    Measured: 2.5 years

  12. 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

    Measured: 2.5 years

  13. In Vitro Diagnostic (IVD) Assay for Screening

    Development and validation of the MAGE-A4 antigen expression companion diagnostic assay

    Measured: 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2019
  2. Study start13 Aug 2019
  3. Primary completion29 Aug 2021
  4. Study completion1 Apr 2038 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04044768
Sponsor's protocol ID
ADP 0044-002
Status last verified
Aug 2026
First submitted
9 Jul 2019
Last updated
26 Aug 2026
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38554725

  • 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.

    PubMed 32002290

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing afamitresgene autoleucel (previously ADP-A2M4) in people with Synovial Sarcoma and Myxoid Liposarcoma, run by USWM CT, LLC at 26 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, France, Spain, United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (Cohort 1) (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04044768, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

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