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

Phase 2Active Not RecruitingNCT03967223

Adaptimmune103 enrolled

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

103

Conditions

Neoplasms

Interventions

Letetresgene autoleucel (lete-cel, GSK3377794)DRUG

letetresgene autoleucel will be administered.

FludarabineDRUG

Fludarabine will be used as the lymphodepleting chemotherapy

CyclophosphamideDRUG

Cyclophosphamide will be used as the lymphodepleting chemotherapy.

Eligibility

Sex: ALLMin age: 10 Years

Medical Language ↔ Plain English

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.

Locations (38)

Outcomes

Primary Outcomes

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.

Time frame: Until disease progression (up to 5 years)

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.

Time frame: Up to 5 years

Secondary Outcomes

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.

Time frame: Until disease progression (up to 5 years)

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.

Time frame: Until disease progression (up to 5 years)

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.

Data from ClinicalTrials.gov

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City of Hope National Medical Center

Duarte, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

Sarah Cannon Research Institute

Denver, Colorado, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

University of Chicago

Chicago, Illinois, United States

University of Iowa College of Medicine

Iowa City, Iowa, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Minnesota Oncology Hematology

Minneapolis, Minnesota, United States

...and 28 more locations