Evaluation of Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

USWM CT, LLC38 sites in 7 countries87 target enrollmentDecember 31, 2019

ConditionsNeoplasms

InterventionsLetetresgene autoleucel (Lete-Cel (GSK3377794))Cyclophosphamide Fludarabine

DrugsExperimental: Letetresgene autoleucel

Overview

Phase: Phase 2
Intervention: Letetresgene autoleucel (Lete-Cel (GSK3377794))
Conditions: Neoplasms
Sponsor: USWM CT, LLC
Enrollment: 87
Locations: 38
Primary Endpoint: ORR (Overall Response Rate)
Status: Active, not recruiting
Last Updated: 24 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

December 31, 2019

End Date

July 31, 2026

Last Updated

24 days ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

USWM CT, LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participant must be ≥10 years of age at the time of signing the informed consent.
•Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg.
•Participant has a diagnosis of synovial sarcoma or myxoid/round cell liposarcoma, confirmed by local histopathology with evidence of disease-specific translocation.
•Participant has advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma. Unresectable refers to a tumor lesion in which clear surgical excision margins cannot be obtained without leading to significant functional compromise.
•Male or female. Contraception requirements will apply at the time of leukapharesis and treatment.
•Life expectancy ≥24 weeks
•Participant has confirmed evidence of a relevant disease-specific translocation per below:
•For synovial sarcoma, presence of a translocation involving chromosome 18 (SYT gene) and/or chromosome X (SSX1, SSX2 or SSX4 genes).
•For myxoid/round cell liposarcoma, presence of a translocation involving chromosome 12 (DDIT3 gene) and/or chromosome 16 (FUS gene) and/or chromosome 22 (EWSR1 gene).
•Participant is either currently being treated with or has completed at least one standard-of-care treatment including anthracycline-containing regimens (e.g., doxorubicin alone, doxorubicin with ifosfamide) for advanced (metastatic or inoperable) disease. Participants who are intolerant to anthracycline may receive ifosfamide alone unless intolerant to or ineligible to receive ifosfamide. Participants who received anthracycline-based therapy in the neoadjuvant/adjuvant setting and progressed will be eligible.

Exclusion Criteria

•Central nervous system (CNS) metastases.
•Any other prior malignancy that is not in complete remission.
•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
•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) or prior or active demyelinating disease
•Participant has received cytotoxic therapy within 3 weeks prior to lymphodepleting chemotherapy
•Systemic corticosteroids or any other immunosuppressive therapy within 2 weeks prior to lymphodepleting chemotherapy.
•Participant has received ≥50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the Investigator's opinion would predispose patients to prolonged cytopenia after lymphodepletion.

Arms & Interventions

Letetresgene autoleucel

Intervention: Letetresgene autoleucel (Lete-Cel (GSK3377794))

Letetresgene autoleucel

Intervention: Cyclophosphamide

Letetresgene autoleucel

Intervention: Fludarabine

Outcomes

Primary Outcomes

ORR (Overall Response Rate)

Time Frame: 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 Outcomes

DCR (Disease Control Rate)(Up to approximately 36 months)
PFS (Progression Free Survival)(Up to approximately 54 months)
OS (Overall survival)(up to 15 years post-T-cell infusion)
DOR (Duration of response)(Up to approximately 54 months)
TTR (Time to response)(Up to approximately 54 months)
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(Up to approximately 54 months)
Number of Participants with AEs of Special Interest (AESIs)(Up to approximately 54 months)
Number of Participants with TEAEs and TESAEs by Severity(Up to approximately 54 months)
Number of Participants with AESIs by Severity(Up to approximately 54 months)
Percentage of Participants with Replication Competent Lentivirus (RCL) Positive(Up to approximately 54 months)
Instances of Insertional Oncogenesis (IO)(Up to approximately 54 months)
Maximum Transgene Expansion (Cmax)(Day 1 to Day 14)
Time to Cmax (Tmax)(Day 1 to Day 14)
Area Under the Time Curve from Zero to Time 28 Days (AUC [0-28])(Up to 28 days)