Description:
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
and Cohort 2) or MRCLS (Cohort 1) .
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
ADP 0044-002
- NCT ID:
NCT04044768
Conditions
- Synovial Sarcoma
- Myxoid Liposarcoma
Purpose
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
and Cohort 2) or MRCLS (Cohort 1) .
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells | Experimental | | |
Eligibility Criteria
Key Inclusion Criteria
- Age ≥16 and <=75 years
- Diagnosis of advanced synovial sarcoma (Cohort 1 and Cohort 2) 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.
- HLA-A*02 positive
- Tumor shows MAGE-A4 expression confirmed by central laboratory.
- ECOG Performance Status of 0 or1.
- Left ventricular ejection fraction (LVEF) ≥50%.
Note: other protocol defined Inclusion criteria may apply
Key Exclusion Criteria:
- HLA-A*02:05 in either allele
- 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.
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 16 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Efficacy: Overall Response Rate (ORR) |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 |
Secondary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs |
| Measure: | Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | Evaluation of RCL using PCR -based assay in peripheral blood. |
| Measure: | Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs). |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs ) |
| Measure: | Efficacy: Best overall response (BOR) |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | BOR is per RECIST V1.1. |
| Measure: | Time to response (TTR) |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of Response (DoR) |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death. |
| Measure: | Overall Survival (OS) |
| Time Frame: | 15 years |
| Safety Issue: | |
| Description: | OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death |
| Measure: | Quantitation of genetically engineered T-cells in PBMCs |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | Quantitation of genetically engineered T-cells in PBMCs by qPCR |
| Measure: | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry |
| Measure: | Quantitation of genetically engineered T-cells in PBMCs |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | Quantitation of genetically engineered T-cells in PBMCs by flow cytometry |
| Measure: | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR |
| Measure: | Invitro diagnostic (IVD) assay for screening |
| Time Frame: | 2.5 years |
| Safety Issue: | |
| Description: | Development and validation of the MAGE-A4 antigen expression companion diagnostic assay |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Adaptimmune |
Trial Keywords
- Cell Therapy
- T Cell Therapy
- SPEAR T Cell
- Sarcoma
- MRCLS
- MAGE A-4
- Immuno-oncology
Last Updated
June 21, 2021
