Clinical trial NCT05993299: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Neoplasms
Keywords: Adoptive T-cell therapy
Letetresgene autoleucel
Lete-cel
GSK3377794
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2023-08-15
Enrollment: 7
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 36 months
Secondary outcomes:
measure: Time to Response (TTR)
timeFrame: Up to approximately 54 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 54 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 36 months
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 54 months
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Up to approximately 54 months
measure: Number of Participants With AEs of Special Interest (AESIs)
timeFrame: Up to approximately 54 months
measure: Number of Participants With TEAEs and TESAEs by Severity
timeFrame: Up to approximately 54 months
measure: Number of Participants With AESIs by Severity
timeFrame: Up to approximately 54 months
measure: Percentage of Participants With Replication Competent Lentivirus (RCL) Positive
timeFrame: Up to approximately 54 months
measure: Instances of Insertional Oncogenesis (IO)
timeFrame: Up to approximately 54 months
measure: Maximum Transgene Expansion (Cmax)
timeFrame: Day 1 to Day 14
measure: Time to Cmax (Tmax)
timeFrame: Day 1 to Day 14
measure: Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa College of Medicine
state: Iowa
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering cancer center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University-Columbus
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Hillman Cancer centre
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: University Of Texas Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Montreal
country: Canada
facility: CIUSSS de L'Est-De-Lile-De-Montreal
state: Quebec
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Lyon cedex
country: France
facility: Centre Léon Bérard
city: Pessac, Cedex
country: France
facility: CHU de Bordeaux GH Sud Hôpital Haut Lévêque
city: Milano
country: Italy
facility: Fondazione IRCCS Instituto Nazionale Dei Tumori
city: Romano Di Lombardia
country: Italy
facility: Ircss Istituto Clinico Humanitas
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Barcelona
country: Spain
facility: Hospital Santa Creu Y Sant Pau
city: Hospitalet de Llobregat, Barcelona
country: Spain
facility: Ico Duran y Reynals l'Hospitalet de Llobrega
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Sevilla
country: Spain
facility: Hospital Virgen Del Rocio
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: London
country: United Kingdom
facility: University College Hospital-London
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
Study officials:
References: