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

NCT03709706 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 208471
• Study Type: interventional
• Target: 34
• Locations: 5 countries
• Sites: 31

Brief Summary

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

Conditions

Neoplasms

Keywords

GSK3377794; Pembrolizumab; T Cell Receptors; Adoptive T-cell therapy; Non-Small Cell Lung Cancer; Immuno-oncology; NY-ESO-1; LAGE-1a; Leukapheresis; Letetresgene autoleucel

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs which start or worsen on or after T-cell infusion are defined as treatment-emergent.

  Up to approximately 10 months

• Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)

  AESI included cytokine release syndrome (CRS), pneumonitis/pneumonia, graft vs host disease (GvHD), guillain barre syndrome (GBS) or acute inflammatory demyelinating polyneuropathy (AIDP), pancytopenia/aplastic anemia (including analysis of all hematopoietic cytopenias), immune effector cell-associated neurotoxicity syndrome (ICANS) and treatment-related inflammatory response at tumor site. AEs which start or worsen on or after T-cell infusion are defined as treatment-emergent.

  Up to approximately 10 months

• Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades

  An AE is any untoward medical occurrence in a clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs which start or worsen on or after T-cell infusion are defined as TE. Severity was reported during study and was assigned a grade according to the National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). SAEs are subset of AEs. AEs and SAEs severity graded on a 5-point scale as: 1 = mild, 2 = moderate discomfort, 3 = severe, 4 = life-threatening and 5 = death due to AE.

  Up to approximately 10 months

• Number of Participants With AEs Leading to Dose Delays

  An AE is any untoward medical occurrence in a clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to dose delays were summarized.

  Up to approximately 10 months

• Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

  Overall response rate (ORR) defined as the percentage of participants with a complete response (CR) or partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria in Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.

  Up to approximately 10 months

Secondary Outcomes (7)

• Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment

  Up to approximately 10 months

• Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment

  Up to approximately 10 months

• Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment

  Up to approximately 10 months

• Time to Response (TTR) Per RECIST Version 1.1 by Investigator Assessment

  Up to approximately 10 months

• Maximum Transgene Expansion (Cmax) of Lete-cel

  Day 1 to Day 15

Study Arms (3)

Arm A: lete-cel monotherapy

EXPERIMENTAL

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.

Drug: Lete-cel; Drug: Pembrolizumab

Arm B: lete-cel plus pembrolizumab

EXPERIMENTAL

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

Drug: Lete-cel; Drug: Pembrolizumab

Arm C: lete-cel plus pembrolizumab

EXPERIMENTAL

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

Drug: Lete-cel; Drug: Pembrolizumab

Interventions

Lete-cel DRUG

lete-cel will be administered to eligible participants.

Arm A: lete-cel monotherapy; Arm B: lete-cel plus pembrolizumab; Arm C: lete-cel plus pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be administered to eligible participants.

Arm A: lete-cel monotherapy; Arm B: lete-cel plus pembrolizumab; Arm C: lete-cel plus pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (31)

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

La Jolla, California, 92093-0987, United States

Location

GSK Investigational Site

Sacramento, California, 95817, United States

Location

GSK Investigational Site

Stanford, California, 94305, United States

Location

GSK Investigational Site

Denver, Colorado, 80218, United States

Location

GSK Investigational Site

Hollywood, Florida, 33021, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30322, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Iowa City, Iowa, 52242, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40536, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15232, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84112-5550, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 1X6, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 0A9, Canada

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Groningen, 9713 GZ, Netherlands

Location

GSK Investigational Site

Rotterdam, 3015 GD, Netherlands

Location

GSK Investigational Site

Utrecht, 3584 CX, Netherlands

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

London, WC1E 6AG, United Kingdom

Location

GSK Investigational Site

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open-label study. Hence, there will be no masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive GSK3377794, either as monotherapy or in combination with pembrolizumab.

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 17, 2018
• Study Start: December 31, 2018
• Primary Completion: June 27, 2022
• Study Completion: November 4, 2022
• Last Updated: February 23, 2024
• Results First Posted: August 7, 2023

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months

Locations

CA (2); US (20); ES (3); GB (2); NL (4)