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Active, Not Recruiting

NCT Number: NCT04044768

Spearhead 1 Study 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) .

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Synovial Sarcoma Liposarcoma Liposarcoma, Myxoid Myxoid Liposarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Adipose Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Sarcoma Sarcoma, Synovial

Age range

10 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Princess Margaret Cancer Centre, Toronto, Ontario, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Primary outcomes

  1. 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.

    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)

Secondary outcomes

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

    Time frame: 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).

    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.

  2. The Number of Participants With Replication Competent Lentivirus (RCL)

    Time frame: 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).

    The presence of RCL was assessed by qPCR targeting a segment of the vesicular stomatitis virus glycoprotein (VSV G) coding sequence.

  3. Insertional Oncogenesis (IO)

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

    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.

  4. Best Overall Response (BOR) (Cohort 1)

    Time frame: 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.

    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.

  5. Time to Response (TTR) (Cohort 1)

    Time frame: 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.

    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.

  6. Duration of Response (DoR) (Cohort 1)

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

    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

  7. Progression Free Survival (PFS) (Cohort 1)

    Time frame: 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

    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.

  8. Overall Survival (OS) (Cohort 1)

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

    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

  9. Peak Persistence (Cohort 1)

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

    Peak persistence of afamitresgene autoleucel cells was reported as vector copy numbers per microgram of genomic DNA from peripheral blood mononuclear cell (PBMC).

  10. 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

  11. Quantitation of Genetically Engineered T-cells in PBMCs

    Time frame: 2.5 years

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

  12. 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

  13. In Vitro Diagnostic (IVD) Assay for Screening

    Time frame: 2.5 years

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

Sponsors and collaborators

Lead sponsor

USWM CT, LLC

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2021
Study completion
2038
First posted
Aug 5, 2019
Registry last updated
Feb 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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