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

• ClinicalTrials.gov Identifier: NCT04044768
• Recruitment Status: Recruiting
• First Posted: August 5, 2019
• Last Update Posted: February 20, 2024
• Sponsor: Adaptimmune
• Information provided by (Responsible Party): Adaptimmune

Tracking Information

• First Submitted Date: July 9, 2019
• First Posted Date: August 5, 2019
• Last Update Posted Date: February 20, 2024
• Actual Study Start Date: August 13, 2019
• Actual Primary Completion Date: October 10, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 1, 2019)

Efficacy: Overall Response Rate (ORR) [ Time Frame: 2.5 years ]

ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 16, 2024)

• Number of subjects with treatment -related adverse events (AEs), including serious adverse events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: 2.5 years ]
  Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs)
• Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells [ Time Frame: 15 years ]
  Evaluation of RCL using PCR -based assay in peripheral blood.
• Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs). [ Time Frame: 2.5 years ]
  Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs )
• Efficacy: Best overall response (BOR) [ Time Frame: 2.5 years ]
  BOR is per RECIST V1.1.
• Time to response (TTR) [ Time Frame: 2.5 years ]
  For patients who are observed to respond to ADP-A2M4, the time taken from date of infusion to achieve a partial response or complete response (TTR) is assessed.
• Duration of Response (DoR) [ Time Frame: 2.5 years ]
  For patients who are observed to respond to ADP-A2M4, the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression per RECIST v 1.1 or death.
• Progression Free Survival (PFS) [ Time Frame: 2.5 years ]
  PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death.
• Overall Survival (OS) [ Time Frame: 15 years ]
  OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death
• Quantitation of genetically engineered T-cells in PBMCs [ Time Frame: 2.5 years ]
  Quantitation of genetically engineered T-cells in PBMCs by qPCR
• 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
• Quantitation of genetically engineered T-cells in PBMCs [ Time Frame: 2.5 years ]
  Quantitation of genetically engineered T-cells in PBMCs by flow cytometry
• 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
• In vitro diagnostic (IVD) assay for screening [ Time Frame: 2.5 years ]
  Development and validation of the MAGE-A4 antigen expression companion diagnostic assay

Original Secondary Outcome Measures (submitted: August 1, 2019)

• Number of subjects with treatment -related adverse events (AEs), including serious adverse events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: 2.5 years ]
  Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs
• Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells [ Time Frame: 2.5 years ]
  Evaluation of RCL using PCR -based assay in peripheral blood.
• Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs). [ Time Frame: 2.5 years ]
  Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs )
• Efficacy: Best overall response (BOR) [ Time Frame: 2.5 years ]
  BOR is per RECIST V1.1.
• Time to response (TTR) [ Time Frame: 2.5 years ]
  For patients who are observed to respond to ADP-A2M4, the time taken from date of infusion to achieve a partial response or complete response (TTR) is assessed.
• Duration of Response (DoR) [ Time Frame: 2.5 years ]
  For patients who are observed to respond to ADP-A2M4, the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression per RECIST v 1.1 or death.
• Progression Free Survival (PFS) [ Time Frame: 2.5 years ]
  PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death.
• Overall Survival (OS) [ Time Frame: 15 years ]
  OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death
• Quantitation of genetically engineered T-cells in PBMCs [ Time Frame: 2.5 years ]
  Quantitation of genetically engineered T-cells in PBMCs by qPCR
• 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
• Quantitation of genetically engineered T-cells in PBMCs [ Time Frame: 2.5 years ]
  Quantitation of genetically engineered T-cells in PBMCs by flow cytometry
• 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
• Invitro diagnostic (IVD) assay for screening [ Time Frame: 2.5 years ]
  Development and validation of the MAGE-A4 antigen expression companion diagnostic assay

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
• 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
• 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) .
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Synovial Sarcoma
• Myxoid Liposarcoma

Intervention

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

Study Arms

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

Intervention: Genetic: afamitresgene autoleucel (previously ADP-A2M4)

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 11, 2023): 120
• Original Estimated Enrollment (submitted: August 1, 2019): 60
• Estimated Study Completion Date: April 1, 2038
• Actual Primary Completion Date: October 10, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Adaptimmune Patient Enquiries; 215-825-9260; patients@adaptimmune.com

• Listed Location Countries: Canada, France, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04044768
• Other Study ID Numbers: ADP 0044-002
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Adaptimmune
• Original Responsible Party: Same as current
• Current Study Sponsor: Adaptimmune
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dejka Araujo, MD; MD Anderson Cancer Center; Houston TX 77030

• PRS Account: Adaptimmune
• Verification Date: February 2024