Clinical trial NCT06703346: Study to Evaluate 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Neoplasms
Keywords: Adoptive T-cell therapy
Letetresgene autoleucel
Lete-cel
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2024-11-25
Enrollment: 87
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 ≥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.

Participant must be positive for HLA-A\*02:01, HLA-A\*02:05, and/or HLA-A\*02:06 alleles by a validated test in a designated central lab prior to leukapheresis Participant's tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+ by immunohistochemistry.

Left ventricular ejection fraction ≥45% with no evidence of clinically significant pericardial effusion.

Performance status: for participants \<16 years of age, Lansky \>60, or for participants ≥16 and \<18 years of age, Karnofsky \>60, or for participants ≥18 years of age, Eastern Cooperative Oncology Group (ECOG) of 0-1.

Participant must have adequate organ function and blood cell counts, within 7 days prior to the day of the leukapheresis procedure Participant is fit for leukapheresis and has adequate venous access for the cell collection Female participants of childbearing potential (FCBP) must have a negative urine or serum pregnancy test.

Participant has measurable disease according to RECIST v1.1. Participant has documented radiographic evidence of disease progression from prior line of therapy.

A biopsy (excisional, incisional, or core) of non-target tumor tissue obtained within 28 days prior to initiating lymphodepleting chemotherapy is mandatory if clinically feasible. This biopsy will be used as baseline for biomarker analyses. If it is not feasible to obtain a fresh biopsy, an archival tumor tissue (FFPE block) taken preferably after completion of the participant's last line of therapy, preferably within 90 days prior to initiating lymphodepleting chemotherapy, may be accepted.

A haematologist has been consulted prior to lymphodepletion in participants who have had a serious/significant bleeding/thrombosis history.

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.

All of the participant's measurable lesions have been irradiated within 3 months prior to lymphodepletion. An irradiated measurable lesion with unequivocal progression following irradiation may be considered a target lesion regardless of time from last radiotherapy dose.

Participant has received an anti-cancer vaccine within 2 months in the absence of tumor response. The participant should be excluded if their disease is responding to an experimental vaccine given within 6 months.

Participant has received live vaccine within 4 weeks prior to lymphodepletion or intends to receive live vaccine during the 3-month period following administration of lete-cel.

Participant has received immune therapy (monoclonal antibody therapy, checkpoint inhibitors) within 4 weeks of lymphodepletion.

Participant had major surgery ≥28 days of first dose of study intervention

Primary outcomes:
measure: ORR (Overall Response Rate)
timeFrame: Up to approximately 36 months
Secondary outcomes:
measure: DCR (Disease Control Rate)
timeFrame: Up to approximately 36 months
measure: PFS (Progression Free Survival)
timeFrame: Up to approximately 54 months
measure: OS (Overall survival)
timeFrame: up to 15 years post-T-cell infusion
measure: DOR (Duration of response)
timeFrame: Up to approximately 54 months
measure: TTR (Time to response)
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: Sarah Cannon Research Institute
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: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de L'Est-De-Lile-De-Montreal
state: Quebec
city: Lyon cedex 08
country: France
facility: Centre Léon Bérard
city: Pessac cedex
country: France
facility: CHU de Bordeaux GH Sud Hôpital Haut Lévêque
city: Milan
country: Italy
facility: Fondazione IRCCS Instituto Nazionale Dei Tumori
state: Lombardia
city: Rozzano (MI)
country: Italy
facility: Ircss Istituto Clinico Humanitas
state: Lombardia
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Barcelona
country: Spain
facility: Hospital Santa Creu Y Sant Pau
city: 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: