Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
- Conditions
- Myxoid LiposarcomaSynovial Sarcoma
- Interventions
- Genetic: afamitresgene autoleucel (previously ADP-A2M4)
- Registration Number
- NCT04044768
- Lead Sponsor
- Adaptimmune
- 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 52
Not provided
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells afamitresgene autoleucel (previously ADP-A2M4) -
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) (Cohort 1) 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 Outcome Measures
Name Time Method Best Overall Response (BOR) (Cohort 1) 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.
Duration of Response (DoR) (Cohort 1) 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 studyProgression Free Survival (PFS) (Cohort 1) 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.
Adverse Events (AE) Including Serious Adverse Events (SAE), SAE, and Adverse Events of Special Interest (AESI) (Cohort 1) 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.
The Number of Participants With Replication Competent Lentivirus (RCL) 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.
Insertional Oncogenesis (IO) 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.
Time Taken to Achieve Peak Expansion of Genetically Engineered T-cells in PBMCs 2.5 years Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR
Time to Response (TTR) (Cohort 1) 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.
Overall Survival (OS) (Cohort 1) 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 studyPeak Persistence (Cohort 1) 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).
Quantitation of Genetically Engineered T-cells in PBMCs 2.5 years Quantitation of genetically engineered T-cells in PBMCs by flow cytometry
In Vitro Diagnostic (IVD) Assay for Screening 2.5 years Development and validation of the MAGE-A4 antigen expression companion diagnostic assay
Trial Locations
- Locations (26)
City of Hope
🇺🇸Duarte, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Northwestern University Robert H. Lurie Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
National Cancer Institute
🇺🇸Bethesda, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Centre Leon Berard
🇫🇷Lyon, France
Vanderbilt
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutch
🇺🇸Seattle, Washington, United States
Medical College of WI Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hospital Haut Leveque, CHU Bordeaux
🇫🇷Pessac, France
Gustave Roussy Cancer Center
🇫🇷Villejuif, France
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Cataluna, Spain
Start Madrid-FJD, Fundación Jimѐnez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
UCLH Cancer Clinical Trials Unit
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom