Clinical trial NCT03967223: Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors
Official title: Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, Alone or in Combination With Other Agents, in HLA-A2+ Participants With NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Neoplasms
Keywords: Adoptive T-cell therapy
Advanced metastatic disease
Advanced unresectable disease
Synovial sarcoma
Myxoid/round cell liposarcoma
GSK3377794
Positive solid tumors
T-cell receptors
Leukapheresis
Letetresgene autoleucel
Lete-cel
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2019-05-30
Enrollment: 103
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.

Detailed description: New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T cells directed against NY-ESO-1/LAGE-1a have shown objective responses. Letetresgene autoleucel (lete-cel, GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor engineered T cells. This is a master protocol investigating T-cell therapies. It will initially consist of a core protocol with two independent substudies investigating Letetresgene autoleucel in previously untreated (1L) Human Leukocyte Antigen (HLA)-A\*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS) (Substudy 1) and Letetresgene autoleucel as second line or higher (2L+) treatment in HLA-A\*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) SS or MRCLS who have progressed following treatment with anthracycline based chemotherapy (Substudy 2).

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: Substudy 1: Overall response rate (ORR)
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 2: Overall response rate (ORR) as assessed by central independent review
timeFrame: Up to 5 years
Secondary outcomes:
measure: Substudy 1 and 2: Time to response (TTR)
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Duration of response (DOR)
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Disease control rate (DCR)
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Progression free survival (PFS)
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL)
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Number of participants with insertional oncogenesis (IO)
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel
timeFrame: Until disease progression (up to 5 years)
measure: Substudy 2: Overall response rate (ORR) as determined by the local investigators
timeFrame: Up to 5 years
measure: Substudy 2: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel
timeFrame: Up to 36 months
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
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: Milano
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: 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:
affiliation: Adaptimmune
name: Adaptimmune
role: STUDY_DIRECTOR
References: