Loading clinical trials...

TERMINATEDPHASE1/PHASE2

Pilot Immunotherapy Study With Letetresgene Autoleucel (Lete-cel, GSK3377794)T-cells in New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1)/ LAGE-1a-positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab

A Phase 1b/2a Pilot Study to Evaluate the Safety and Tolerability of Autologous T-Cells Expressing Enhanced TCRs (T Cell Receptors) Specific for NY-ESO-1/LAGE-1a (GSK3377794) Alone, or in Combination With Pembrolizumab in HLA-A2+ Participants With NY-ESO-1- or LAGE-1a-Positive Advanced or Recurrent Non-Small Cell Lung Cancer

NCT03709706•GlaxoSmithKline

View on ClinicalTrials.gov

Summary

This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.

Detailed Description

New York esophageal squamous cell carcinoma-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 (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This is a multi-arm, open-label study of letetresgene autoleucel (lete-cel, GSK3377794) in Human Leukocyte Antigen (HLA)-A\*02:01, HLA-A\*02:05 and/or HLA-A\*02:06 positive adults whose tumors express NY-ESO-1 and/or LAGE-1a. This study will enroll participants who have unresectable Stage IIIb or Stage IV NSCLC.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Age \>=18 years on the day of signing informed consent.
•Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC.
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
•Participant is positive for any of the following alleles: human leukocyte antigen (HLA)-A\*02:01, HLA-A\*02:05, and a) or HLA-A\*02:06 by a validated test.
•Participant's tumor meets the pre-defined threshold for expression of NY-ESO-1 and/or LAGE-1a.
•Adequate organ function and blood cell counts, as defined in the protocol.
•Predicted life expectancy that is \>=24 weeks from leukapheresis.
•Left ventricular ejection fraction \>=45%.
•Prior therapies prior to lymphodepletion: a) All participants with NSCLC lacking actionable genetic aberrations, per National Comprehensive Cancer Network (NCCN) guidelines (Arms A and B), need to have received at least one line of programmed death protein 1/programmed death protein 1 ligand (PD-1/PD-L1) checkpoint blockade therapy. For participants in the metastatic setting, PD-1/PD-L1 checkpoint blockade therapy must have been received either alone, in combination or sequentially with platinum-containing chemotherapy. OR b) All participants with NSCLC with actionable genetic aberrations, per NCCN guidelines (Arm C only), should have received appropriate targeted therapy following NCCN or equivalent country-level guidelines.
•Disease progression at time of treatment, as defined in the protocol.
+1 more criteria

Exclusion Criteria

•Prior treatment: 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.
•Prior allogeneic/autologous bone marrow or solid organ transplantation.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, dimethylsulfoxide (DMSO) or other agents used in the study.
•Severe hypersensitivity (\>= Grade 3) to pembrolizumab and/or any of its excipients.
•Active autoimmune disease that has required systemic treatment in past 2 years.
•History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
•Uncontrolled intercurrent illness.
•Participant has active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein Barr virus (EBV), cytomegalovirus (CMV), syphilis, or human T lymphotropic virus (HTLV), as defined in protocol.
•Known psychiatric or substance abuse disorders.
•Symptomatic or untreated central nervous system (CNS) metastases.
+3 more criteria

Locations (31)

GSK Investigational Site

Duarte, California, United States

GSK Investigational Site

La Jolla, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

Stanford, California, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Hollywood, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Iowa City, Iowa, United States

GSK Investigational Site

Lexington, Kentucky, United States

Key Dates

Start Date

December 31, 2018

Primary Completion Date

June 27, 2022

Completion Date

November 4, 2022

Last Updated

February 23, 2024

Enrollment

ACTUAL participants

Conditions

Neoplasms

Interventions

Lete-cel

DRUG

Pembrolizumab

DRUG

A Study to Evaluate LY3537021 for the Treatment of Nausea and Vomiting Caused by Chemotherapy in Adults With Cancer

NCT07169851

NauseaVomiting+2 more

View study

RECRUITINGPHASE3

A Two-Part Phase 3 Study of Sofetabart Mipitecan (LY4170156) in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Part B) Ovarian Cancer

NCT07213804

Ovarian NeoplasmsFallopian Tube Neoplasms+2 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 23, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Pilot Immunotherapy Study With Letetresgene Autoleucel (Lete-cel, GSK3377794)T-cells in New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1)/ LAGE-1a-positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab

Inclusion Criteria

Exclusion Criteria

A Study to Evaluate LY3537021 for the Treatment of Nausea and Vomiting Caused by Chemotherapy in Adults With Cancer

A Two-Part Phase 3 Study of Sofetabart Mipitecan (LY4170156) in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Part B) Ovarian Cancer

Post-operative Medium Chain Triglyceride Diet May Reduce Hospital Stay Following Lung Resection

Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease

Skin Conductance for Predicting Spinal Anesthesia-Induced Hypotension in Geriatric Urologic Oncology Patients

A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer