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

NCT ID: NCT03709706

Last Updated: 2024-02-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-31

Study Completion Date

2022-11-04

Brief Summary

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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

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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.

Conditions

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Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Participants will receive GSK3377794, either as monotherapy or in combination with pembrolizumab.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

This will be an open-label study. Hence, there will be no masking.

Study Groups

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Arm A: lete-cel monotherapy

In Arm A, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel monotherapy. Participants who subsequently progress by Week 25 will be offered pembrolizumab.

Group Type EXPERIMENTAL

Lete-cel

Intervention Type DRUG

lete-cel will be administered to eligible participants.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab will be administered to eligible participants.

Arm B: lete-cel plus pembrolizumab

In Arm B, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.

Group Type EXPERIMENTAL

Lete-cel

Intervention Type DRUG

lete-cel will be administered to eligible participants.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab will be administered to eligible participants.

Arm C: lete-cel plus pembrolizumab

In Arm C, participants with NSCLC (with actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.

Group Type EXPERIMENTAL

Lete-cel

Intervention Type DRUG

lete-cel will be administered to eligible participants.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab will be administered to eligible participants.

Interventions

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Lete-cel

lete-cel will be administered to eligible participants.

Intervention Type DRUG

Pembrolizumab

Pembrolizumab will be administered to eligible participants.

Intervention Type DRUG

Eligibility Criteria

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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.
* Measurable disease at time of treatment per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by local site investigator/radiology.

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.
* Radiotherapy that involves the lung (Percentage of normal lung receiving at least 20 Gray \[Gy\] during radiotherapy \[V20\] exceeding 30% lung volume or mean heart dose \>20 Gy) within 3 months or radiotherapy (including but not limited to palliative radiotherapy) to lung/mediastinum with V20 less than 30% lung volume and with mean heart dose \<=20 Gy within 4 weeks (+/- 3 days).
* Radiotherapy of \>=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 participants to prolonged cytopenia after lymphodepletion.
* All of the participant's measurable lesions have been irradiated within 3 months before lymphodepletion.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Duarte, California, United States

Site Status

GSK Investigational Site

La Jolla, California, United States

Site Status

GSK Investigational Site

Sacramento, California, United States

Site Status

GSK Investigational Site

Stanford, California, United States

Site Status

GSK Investigational Site

Denver, Colorado, United States

Site Status

GSK Investigational Site

Hollywood, Florida, United States

Site Status

GSK Investigational Site

Atlanta, Georgia, United States

Site Status

GSK Investigational Site

Chicago, Illinois, United States

Site Status

GSK Investigational Site

Iowa City, Iowa, United States

Site Status

GSK Investigational Site

Lexington, Kentucky, United States

Site Status

GSK Investigational Site

Baltimore, Maryland, United States

Site Status

GSK Investigational Site

St Louis, Missouri, United States

Site Status

GSK Investigational Site

New York, New York, United States

Site Status

GSK Investigational Site

Durham, North Carolina, United States

Site Status

GSK Investigational Site

Columbus, Ohio, United States

Site Status

GSK Investigational Site

Philadelphia, Pennsylvania, United States

Site Status

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

Site Status

GSK Investigational Site

Nashville, Tennessee, United States

Site Status

GSK Investigational Site

Houston, Texas, United States

Site Status

GSK Investigational Site

Salt Lake City, Utah, United States

Site Status

GSK Investigational Site

Toronto, Ontario, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Amsterdam, , Netherlands

Site Status

GSK Investigational Site

Groningen, , Netherlands

Site Status

GSK Investigational Site

Rotterdam, , Netherlands

Site Status

GSK Investigational Site

Utrecht, , Netherlands

Site Status

GSK Investigational Site

Barcelona, , Spain

Site Status

GSK Investigational Site

Madrid, , Spain

Site Status

GSK Investigational Site

Madrid, , Spain

Site Status

GSK Investigational Site

London, , United Kingdom

Site Status

GSK Investigational Site

Manchester, , United Kingdom

Site Status

Countries

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United States Canada Netherlands Spain United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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208471

Identifier Type: -

Identifier Source: org_study_id

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