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

Phase 2Active Not RecruitingNCT05993299

Adaptimmune7 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms

Interventions

Letetresgene autoleucelDRUG

Letetresgene autoleucel will be administered.

CyclophosphamideDRUG

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

FludarabineDRUG

Fludarabine will be used as a lymphodepleting chemotherapy.

Eligibility

Sex: ALLMin age: 10 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Locations (38)

Outcomes

Primary Outcomes

Overall Response Rate (ORR)

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.

Time frame: Up to approximately 36 months

Secondary Outcomes

Time to Response (TTR)

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).

Time frame: Up to approximately 54 months

Duration of Response (DOR)

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).

Data from ClinicalTrials.gov

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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

...and 28 more locations

Time frame: Up to approximately 54 months

Disease Control Rate (DCR)

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.

Time frame: Up to approximately 36 months

Progression Free Survival (PFS)

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.

Time frame: Up to approximately 54 months

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Time frame: Up to approximately 54 months

Number of Participants With AEs of Special Interest (AESIs)

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.

Time frame: Up to approximately 54 months

Number of Participants With TEAEs and TESAEs by Severity

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.

Time frame: Up to approximately 54 months

Number of Participants With AESIs by Severity

Time frame: Up to approximately 54 months

Percentage of Participants With Replication Competent Lentivirus (RCL) Positive

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).

Time frame: Up to approximately 54 months

Instances of Insertional Oncogenesis (IO)

Instances of Insertional Oncogenesis (IO) was summarized descriptively.

Time frame: Up to approximately 54 months

Maximum Transgene Expansion (Cmax)

Cmax was defined as maximum observed persistence, determined directly from the persistence-time data. Blood samples were collected for PK analysis.

Time frame: Day 1 to Day 14

Time to Cmax (Tmax)

Tmax was defined as time to reach Cmax, determined directly from the persistence-time data. Blood samples were collected for PK analysis.

Time frame: Day 1 to Day 14

Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])

Area under the persistence-time curve from time zero to Day 28. Blood samples were collected for PK analysis.

Time frame: Up to 28 days