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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT05993299

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Letetresgene autoleucel	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of 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

Actual Study Start Date :

Dec 31, 2019

Actual Primary Completion Date :

Oct 12, 2022

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Letetresgene autoleucel	Drug: Letetresgene autoleucel Letetresgene autoleucel will be administered.

Arm

Intervention/Treatment

Experimental: Letetresgene autoleucel

Drug: Letetresgene autoleucel

Letetresgene autoleucel will be administered.

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [Up to approximately 36 months]
Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants within the analysis population per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. as determined by the local investigators.

Secondary Outcome Measures

Time to response (TTR) [Up to approximately 53 months]
Time to response is defined as time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by local investigators per RECIST v1.1.
Duration of response (DOR) [Up to approximately 53 months]
Duration of response is defined as, in the subset of participants who show a confirmed CR or PR as assessed by local investigators, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
Disease control rate (DCR) [Up to approximately 53 months]
Disease control rate is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with minimal 12 weeks duration as determined by local investigators per RECIST v1.1 relative to the total number of participants within the analysis population.
Progression free survival (PFS) [Up to approximately 53 months]
Progression free survival is defined as the time from the date of T-cell administration until first documented sign of disease progression per RECIST v1.1, or death.
Number of Participants with adverse events (AEs), serious adverse events (SAEs) according to severity [Up to approximately 53 months]
AEs, SAEs and AESIs will be collected. Severity of AEs and SAEs will be summarized using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Number of Participants with AEs of special interest (AESI) according to severity [Up to approximately 53 months]
Number of participants with replication competent lentivirus (RCL) [Up to approximately 53 months]
Number of participants with insertional oncogenesis (IO) [Up to approximately 53 months]
Maximum transgene expansion (Cmax) of letetresgene autoleucel [Up to approximately 53 months]
Time to Cmax (Tmax) of letetresgene autoleucel [Up to approximately 53 months]
Area under the concentration time curve from zero to time 28 days (AUC[0-28]) of letetresgene autoleucel [Up to 28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must be greater than or equal to 10 years of age on the day of signing informed consent.
Participant must be positive for HLA-A02:01, HLA-A02:05, 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.
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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15232
2	GSK Investigational Site	Dallas	Texas	United States	75390-9063
3	GSK Investigational Site	Milwaukee	Wisconsin	United States	53226
4	GSK Investigational Site	Montreal	Quebec	Canada	H1T 2M4
5	GSK Investigational Site	Amsterdam		Netherlands	1066 CX
6	GSK Investigational Site	London		United Kingdom	SW3 6JJ