A Phase II Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma.

Study Identifier:
ADP-0044-002
CT.gov Identifier:
NCT04044768
EudraCT Identifier:
2019-000589-39
EU Trial (CTIS) Number:
2024-512847-21-00
Study Contact Information:
(210) 593-5651 or [email protected]
Study Complete

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Study Summary

To evaluate ADP-A2M4 patients with synovial sarcoma and myxoid round cell liposarcoma (hla-a*02 & mage-a4 antigen positive) who have received prior chemotherapy.

To evaluate the efficacy, safety and tolerability of ADP-A2M4 SPEAR T-cells.

To evaluate genetically-engineered ADP-A2M4 in HLA-A*02 subjects with metastatic or inoperable (advanced) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma (MRCLS) who have received prior chemotherapy and whose tumor expresses the MAGE-A4 tumor antigen.

To evaluate the efficacy, safety and tolerability of ADP-A2M4 in patients with advanced/metastatic SS or MRCLS who are HLA-A*02 positive and whose tumors express the MAGE-A4 protein.

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 and Cohort 2) or MRCLS (Cohort 1).

To support the continued investigation of potential mechanisms of response and acquired resistance in SS and MRCLS patients, ongoing translational analyses, described in more detail below, are being performed.

Tumor biopsy sample analyses includes duplexed TCR RNAscope, anti-CD3 IHC analysis, and multiplex immunofluorescence for spatial analyses of T-cell infiltration in context with tumor microenvironment (TME) molecular profiling.

To evaluate the efficacy and safety of afami-cel in pretreated pts with advanced/metastatic synovial sarcoma (Cohorts 1 and 2) or myxoid/round cell

liposarcoma (Cohort 1).

To report updated interim mOS data in pts with advanced synovial sarcoma in Cohort 1

To evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel's engineered TCR T-cells target MAGE-A4+ tumors.

The primary efficacy analysis is for Cohort 1 only. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses. Cohort 2 has an overall response rate nearly identical to Cohort 1 (data will be reported when follow-up is mature). Cohort 3 is now open to provide access to afami-cel ahead of planned commercialization.

The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Soft Tissue Sarcoma
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    II
    Sex
    Female & Male
    Age
    10 - 75 Years
    Study Drug
  • Drug: Experimental: Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR T cells
    • Read More
  • Drug: Patients will receive doses of up to 10 billion ADP-A2M4 SPEAR T-cells and the lymphodepletion regimen of fludarabine (30 mg/m^2/day for 4 days) and cyclophosphamide (600 mg/m^2/day for 3 days). Following apheresis, T-cells are isolated, transduced with MAGEA4c1032TCR, and expanded. Prior to infusion, patients will receive lymphodepletion consisting of fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (600 mg/m2/day x 3 days). Patients will receive 1 - 10 × 10^9 transduced T-cells. Disease will be assessed by independent review per RECIST v1.1 by CT/MRI at weeks 4, 8, 12, 16, 24, and every 2 months thereafter until confirmed disease progression.
  • Drug: ASCO 2020:
  • Drug: Patients undergo leukapheresis for collection of autologous T-cells for processing and manufacture into afamitresgene autoleucel cells. Pts were treated with afamitresgene autoleucel doses between 1-10 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.
  • Drug: ASCO 2023:
  • Drug: Approximately 90 patients were planned to be treated: 45 in Cohort 1 and 45 in Cohort 2.
  • Drug: Eligible patients received a single dose of afami-cel between 1-10 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.
  • Drug: 44 patients with advanced synovial sarcoma were treated with a single dose of afami-cel after undergoing lymphodepleting chemotherapy with cyclophosphamide and fludarabine
  • Drug: Patients received a single intravenous dose of afami-cel (transduced dose range 10×109-100×109 T cells) after lymphodepletion.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    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
    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.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Soft Tissue Sarcoma