Synovial sarcoma, Myxoid round cell liposarcoma MedDRA version: 20.0 Level: PT Classification code 10075333 Term: Soft tissue sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10075333 Term: Soft tissue sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: ADP-A2M4
Product Code: ADP-A2M4
Pharmaceutical Form: Infusion
Current Sponsor code: ADP-A2M4
Sponsors
Adaptimmune LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject (or legally authorized representative) voluntarily agrees to participate by giving written Informed Consent (and Assent as applicable)in accordance with ICH GCP guidelines and applicable local regulations. 2. Subject (or legally authorized representative) agrees to abide by all protocol required procedures including study related assessments and management by the treating institution for the duration of the study, including long term follow-up. 3. Age =16 and =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Positive for HLA-A*02:05 in either allele via Adaptimmune designated central laboratory testing. HLA-A*02 alleles having the same protein sequence as HLA-A*02:05 in the peptide binding domain (P groups) will also be excluded. Other alleles may be exclusionary after adjudication with the sponsor. 2. Received or plans to receive therapy/treatment prior to leukaphereseisis or lymphodepleting chemotherapy 3. Toxicity from previous anti-cancer therapy must have recovered to = Grade 1 prior to enrollment (except for nonclinically significant toxicities, e.g., alopecia, vitiligo). Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g. peripheral neuropathy) can be enrolled. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study. 5. History of autoimmune or immune mediated disease. Subjects with hypothyroidism, diabetes, adrenal insufficiency or pituitary insufficiency that are stable on replacement therapy are eligible. Subjects with disorders such as asthma, psoriasis or atopic dermatitis that are well controlled without requiring systemic immunosuppression are also eligible. 6. Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases. Subjects with a prior history of symptomatic CNS metastases must have received treatment (i.e., stereotactic radiosurgery (SRS), whole brain radiation (WBRT) or surgery) and be neurologically stable for at least 1 month, not requiring anti-seizure medications and off of steroids for at least 14 days prior to leukapheresis and lymphodepletion. Antiseizure prophylaxis is permitted. Subjects who have asymptomatic CNS metastases without associated edema, shift, requirement for steroids or anti-seizure medications for the treatment of seizures are eligible. 7. Any other prior malignancy that is not in complete remission. Resectable squamous or basal cell carcinoma of the skin is acceptable. Prior malignancies that have been surgically resected and show no evidence of disease are acceptable. 8. Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection; • Clinically significant cardiac disease defined by congestive heart failure New York Heart Association (NYHA) Class 3 or Class 4; • Uncontrolled clinically significant arrhythmia; Acute Coronary Syndrome (ACS) (angina or MI) in last 6 months; • Interstitial lung disease (subjects with existing pneumonitis as a result of radiation are not excluded, however, subjects must not be oxygen dependent); • Congenital or family history of long QT syndrome; • Current uncontrolled hypertension despite optimal medical therapy; • History of stroke or central nervous system bleeding; transient ischemic attack (TIA) or reversible ischemic neurologic deficit (RIND) in last 6 months; 9. Active infection with HIV, HBV, HCV or HTLV as defined below: • Positive serology for HIV; • Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Subjects who are hepatitis B surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA and receive prophylaxis against viral reactivation. Prophylaxis should be initiated prior to lymphodepleting therapy and continued for 6 months; Active hepatitis C infection as demonstrated by hepatitis C RNA test. Subjects who are HCV antibody positive will be screened for HCV RNA by any RT PCR or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Study secondary objectives are: - To evaluate the safety and tolerability of autologous genetically modified T cells (ADP-A2M4) in HLA-A*02 positive patients with MAGE-A4 expressing advanced synovial sarcoma or MRCLS - To evaluate the efficacy of autologous genetically modified T cells (ADP-A2M4) in HLA-A*02 positive patients with MAGE-A4 expressing advanced synovial sarcoma or MRCLS - Development and validation of an in vitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval - Characterise the in vivo cellular pharmacokinetics (PK) profile of ADPA2M4 cells;Main Objective: The primary objective of this study is to evaluate the efficacy of autologous genetically modified T cells (ADP-A2M4) in HLA-A*02 positive patients with MAGE-A4 expressing advanced synovial sarcoma or MRCLS .;Primary end point(s): Overall Response Rate (ORR) per RECIST v1.1 by independent review;Timepoint(s) of evaluation of this end point: Anytime during the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability • Adverse events (AEs) including serious adverse events (SAEs) • Incidence, severity and duration of the AEs of special interest • Replication Competent Lentivirus (RCL) • T cell Clonality and Insertional oncogenesis (IO). Efficacy • Time to Response (TTR) • Duration of Response (DoR) • Best Overall Response (BOR) • Progression Free Survival (PFS) • Overall Survival (OS). Development and validation of an in vitro diagnostic (IVD) assay • Retention of additional tumor tissue during Pre-screening to enable development and validation of the MAGE-A4 antigen expression companion diagnostic assay PK •Peak persistence and other relevant PK parameters of ADP-A2M4 cells;Timepoint(s) of evaluation of this end point: Anytime during the study | — |
Countries
Canada, France, Spain, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs
Adaptimmune LLC
Outcome results
None listed