Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
- Conditions
- Neoplasms
- Interventions
- Registration Number
- NCT05993299
- Lead Sponsor
- Adaptimmune
- Brief Summary
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors. This trial is a sub study of the Master study NCT03967223.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 7
- Participant must be greater than or equal to 10 years of age on the day of signing informed consent.
- Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg
- Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a designated central laboratory
- Participant's tumor is positive for NY-ESO-1 expression by a designated central laboratory.
- Participant has a diagnosis of synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS)
- Performance status: dependent on age - Lansky > 60, Karnofsky > 60, Eastern
- Cooperative Oncology Group 0-1.
- Participant must have adequate organ function and blood cell counts, within 7 days prior to leukapheresis.
- At time of treatment, participant has measurable disease according to RECIST v1.1.
- Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
- Consultation for prior history per protocol specifications.
- Central nervous system metastases.
- Any other prior malignancy that is not in complete remission.
- Clinically significant systemic illness (.(Serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the participant's ability to tolerate protocol therapy or significantly increase the risk of complications)
- Prior or active demyelinating disease.
- History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn's disease, systemic lupus) requiring steroids or other immunosuppressive treatments.
- Previous treatment with genetically engineered NY-ESO-1-specific T cells.
- Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
- Prior gene therapy using an integrating vector.
- Previous allogeneic hematopoietic stem cell transplant.
- Washout periods for prior radiotherapy and systemic chemotherapy must be followed.
- Participant had major surgery in less than or equal to 28 days of first dose of study intervention.
- Prior radiation exceeds protocol specified limits.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Letetresgene autoleucel Cyclophosphamide - Letetresgene autoleucel Fludarabine - Letetresgene autoleucel Letetresgene autoleucel -
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to approximately 36 months ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline). 95% CI is based on Clopper-Pearson exact confidence interval.
- Secondary Outcome Measures
Name Time Method Time to Cmax (Tmax) Day 1 to Day 14 Tmax was defined as time to reach Cmax, determined directly from the persistence-time data. Blood samples were collected for PK analysis.
Time to Response (TTR) Up to approximately 54 months Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Up to approximately 54 months An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.
Percentage of Participants With Replication Competent Lentivirus (RCL) Positive Up to approximately 54 months RCL was monitored using a polymerase chain reaction (PCR)-based assay that detects and measures copies of the gene coding for the vector's envelope protein, namely vesicular stomatitis virus G protein (VSV-G).
Instances of Insertional Oncogenesis (IO) Up to approximately 54 months Instances of Insertional Oncogenesis (IO) was summarized descriptively.
Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28]) Up to 28 days Area under the persistence-time curve from time zero to Day 28. Blood samples were collected for PK analysis.
Duration of Response (DOR) Up to approximately 54 months Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease as assessed by local investigators, or death among participants with a confirmed response per RECIST 1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline).
Number of Participants With AESIs by Severity Up to approximately 54 months An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included cytokine release syndrome (CRS), hematopoietic cytopenias (including pancytopenia and aplastic anemia), graft vs host disease (GVHD), ICANS, Guillain-Barre syndrome, treatment-related inflammatory response at tumor site(s), and neutropenia Grade 4 lasting ≥28 days.
Disease Control Rate (DCR) Up to approximately 36 months DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with a minimal 12 weeks (84 days ± 7 day window) duration relative to the total number of participants within the analysis population at the time of primary analysis as determined by local investigators per RECIST v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. The disease progression (PD) is defined as the date of radiological disease progression based on imaging data per RECIST v1.1. 95% CI is based on Clopper-Pearson exact confidence interval.
Progression Free Survival (PFS) Up to approximately 54 months PFS is defined as the interval of time between from the date of T-cell infusion to the earliest date of radiological progression of disease (PD) as assessed by local investigator per RECIST v1.1, or death due to any cause. The PD is defined as the date of radiological disease progression based on imaging data per RECIST v1.1.
Number of Participants With AEs of Special Interest (AESIs) Up to approximately 54 months An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included cytokine release syndrome (CRS), hematopoietic cytopenias (including pancytopenia and aplastic anemia), graft vs host disease (GVHD), ICANS, Guillain-Barre syndrome, treatment-related inflammatory response at tumor site(s), and neutropenia Grade 4 lasting ≥28 days.
Number of Participants With TEAEs and TESAEs by Severity Up to approximately 54 months An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs and SAEs were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences; Grade 5- Death related to AE.
Maximum Transgene Expansion (Cmax) Day 1 to Day 14 Cmax was defined as maximum observed persistence, determined directly from the persistence-time data. Blood samples were collected for PK analysis.
Trial Locations
- Locations (38)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Sarah Cannon Research Institute
🇺🇸Denver, Colorado, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Iowa College of Medicine
🇺🇸Iowa City, Iowa, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Minnesota Oncology Hematology
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering cancer center
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Ohio State University-Columbus
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Pittsburgh, Hillman Cancer centre
🇺🇸Pittsburgh, Pennsylvania, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
University Of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
CIUSSS de L'Est-De-Lile-De-Montreal
🇨🇦Montreal, Quebec, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
Centre Léon Bérard
🇫🇷Lyon cedex, France
CHU de Bordeaux GH Sud Hôpital Haut Lévêque
🇫🇷Pessac, Cedex, France
Fondazione IRCCS Instituto Nazionale Dei Tumori
🇮🇹Milano, Italy
Ircss Istituto Clinico Humanitas
🇮🇹Romano Di Lombardia, Italy
The Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
Hospital Santa Creu Y Sant Pau
🇪🇸Barcelona, Spain
Ico Duran y Reynals l'Hospitalet de Llobrega
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Virgen Del Rocio
🇪🇸Sevilla, Spain
Royal Marsden Hospital
🇬🇧London, United Kingdom
University College Hospital-London
🇬🇧London, United Kingdom
Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom