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

Neoplasms Clinical Trial

— IGNYTE-ESO  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03967223
• Other study ID #: 208467
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 31, 2019
• Est. completion date: July 31, 2026

Study information

• Verified date: April 2024
• Source: Adaptimmune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 103
• Est. completion date: July 31, 2026
• Est. primary completion date: August 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Letetresgene autoleucel (lete-cel, GSK3377794)
letetresgene autoleucel will be administered.
• Fludarabine
Fludarabine will be used as the lymphodepleting chemotherapy
• Cyclophosphamide
Cyclophosphamide will be used as the lymphodepleting chemotherapy.

Locations

Country	Name	City	State
Canada	CIUSSS de L'Est-De-Lile-De-Montreal	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	Centre Léon Bérard	Lyon cedex 08
France	CHU de Bordeaux GH Sud Hôpital Haut Lévêque	Pessac cedex
Italy	Fondazione IRCCS Instituto Nazionale Dei Tumori	Milano	Lombardia
Italy	Ircss Istituto Clinico Humanitas	Rozzano (MI)	Lombardia
Netherlands	The Netherlands Cancer Institute	Amsterdam
Spain	Hospital Santa Creu Y Sant Pau	Barcelona
Spain	Ico Duran y Reynals l'Hospitalet de Llobrega	Hospitalet de Llobregat, Barcelona
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Virgen Del Rocio	Sevilla
United Kingdom	Royal Marsden Hospital	London
United Kingdom	University College Hospital-London	London
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University-Columbus	Columbus	Ohio
United States	University Of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Sarah Cannon Research Institute	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Iowa College of Medicine	Iowa City	Iowa
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	Minnesota Oncology Hematology	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering cancer center	New York	New York
United States	University of Pittsburgh, Hillman Cancer Centre	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research	Seattle	Washington
United States	Stanford Hospital and Clinics	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Adaptimmune

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Substudy 1: Overall response rate (ORR)	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 at any time per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. as determined by the local investigators.	Until disease progression (up to 5 years)
Primary	Substudy 2: Overall response rate (ORR) as assessed by central independent review	Overall response rate is defined as the percentage of participants with a confirmed CR or PR relative to the total number of participants within the analysis population at any time per RECIST v1.1. as assessed by central independent review.	Up to 5 years
Secondary	Substudy 1 and 2: Time to response (TTR)	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.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Duration of response (DOR)	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.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Disease control rate (DCR)	Disease control rate is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with minimal 12 weeks duration relative to the total number of participants within the analysis population at the time of primary analysis as determined by Investigators per RECIST v1.1.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Progression free survival (PFS)	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.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity	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.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL)	RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Number of participants with insertional oncogenesis (IO)	Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.	Until disease progression (up to 5 years)
Secondary	Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters	Blood and urine samples will be collected for assessment of hematology, clinical chemistry and urinalysis parameters.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel	Whole blood samples will be collected at indicated time points for evaluation of Cmax.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel	Whole blood samples will be collected at indicated time points for evaluation of Tmax.	Until disease progression (up to 5 years)
Secondary	Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel	Whole blood samples will be collected at indicated time points for evaluation of AUC(0-t).	Until disease progression (up to 5 years)
Secondary	Substudy 2: Overall response rate (ORR) as determined by the local investigators	Overall response rate is defined as the percentage of participants with a confirmed CR or PR relative to the total number of participants within the analysis population at any time per RECIST v1.1. as determined by the local investigators.	Up to 5 years
Secondary	Substudy 2: Overall Survival (OS)	Overall Survival is defined as the interval of time between the date of T-cell infusion and the date of death.	Up to 5 years
Secondary	Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel	Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.	Up to 36 months