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DRUG:

letetresgene autoleucel (GSK3377794)

i
Other names: GSK3377794, NY-ESO-1, NY-ESO-1/LAGE-1-specific T-cells, NY-ESO-1/LAGE-1-modified T-cells, NY-ESO-1c259-modified T cells, NY-ESO SPEAR T-cell therapy, GSK 3377794, '794, NY-ESO TCR, GSK 794, NYESO-1c259, lete-cel
Company:
Adaptimmune
Drug class:
TCR modulator, NY ESO 1 inhibitor
Related drugs:
1m
Trial completion date • Metastases
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
HLA-A*02:01 • HLA-A*02 • CTAG1B expression • HLA-A2 positive
|
cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
7ms
Trial primary completion date • Combination therapy
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
HLA-A*02:01 • HLA-A*02 • CTAG1B expression • HLA-A2 positive
|
cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
9ms
Phase classification • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
HLA-A*02
|
Keytruda (pembrolizumab) • letetresgene autoleucel (GSK3377794)
over1year
PRIMARY ANALYSIS OF EFFICACY AND SAFETY OF LETETRESGENE AUTOLEUCEL (LETE-CEL) AS FIRST-LINE TREATMENT FOR UNRESECTABLE OR METASTATIC SYNOVIAL SARCOMA (SS); SUBSTUDY 1 OF IGNYTE-ESO (CTOS 2023)
Key eligibility criteria were: age ≥10 years; HLA-A*02:01, A*02:05, or A*02:06; NY-ESO-1+ (≥30% of cells 2+/3+); optional bridging therapy consisting of 2 cycles of doxorubicin (dox) between apheresis and lymphodepletion (LD); and measurable disease. Pts received fludarabine (range: 60–120 mg/m^2) and cyclophosphamide (range: 1800–3600 mg/m^2) for LD, and a transduced T-cell dose between 1 to 15x10^9... This study highlights the challenge to enroll advanced/metastatic treatment-naïve rare sarcoma pts in a cell therapy trial, with 7 pts enrolled over ~2.5 years. Encouraging efficacy was seen in a small population of treatment-naïve pts in the advanced/metastatic setting with 80% ORR, with all responses ongoing at the time of this analysis. The TEAEs for SS1 are consistent with the known safety profile of lete-cel.
Clinical • Metastases
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
HLA-A*02
|
doxorubicin hydrochloride • cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
over1year
New P2 trial • Metastases
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
HLA-A*02:01 • HLA-A*02 • CTAG1B expression • HLA-A2 positive
|
cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
almost2years
Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma. (PubMed, Blood Adv)
Two responders, but none of the non-responders, exhibited elevated cytokine levels post lete-cel infusion. Lete-cel had a manageable safety profile consistent with other lete-cel studies and demonstrated clear but transient antitumor activity in patients with RRMM.
Journal
|
HLA-A (Major Histocompatibility Complex, Class I, A) • IL6 (Interleukin 6) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
HLA-A*02 • CTAG1B expression
|
Keytruda (pembrolizumab) • letetresgene autoleucel (GSK3377794)
almost2years
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 (clinicaltrials.gov)
P1b/2a, N=34, Terminated, GlaxoSmithKline | N=54 --> 34 | Trial completion date: May 2025 --> Nov 2022 | Active, not recruiting --> Terminated | Trial primary completion date: May 2025 --> Jun 2022; The study was terminated for reasons pertaining to feasibility
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
HLA-A*02
|
Keytruda (pembrolizumab) • letetresgene autoleucel (GSK3377794)
almost2years
ZENYTH-ESO: Master protocol to assess the safety and recommended phase II dose of next generation NY-ESO-1-specific TCR T-cells in HLA-A*02 patients with synovial sarcoma, myxoid/round cell liposarcoma and non- small cell lung cancer [Substudy 1 (GSK3901961) and Substudy 2 (GSK3845097)] (DKK 2022)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing an affinity-enhanced T-cell recep- tor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. This master protocol will evaluate the safety and efficacy of next generation NY-ESO-1 specific TCR-T cells in SS/MRCLS or NSCLC.
Clinical • P2 data
|
CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • TGFB1 (Transforming Growth Factor Beta 1) • CTAG2 (Cancer/testis antigen 2)
|
HLA-A*02 • CTAG1B expression
|
letetresgene autoleucel (GSK3377794) • GSK3845097 • GSK3901961
almost2years
ZENYTH-ESO Substudy 1 (GSK3901961), Cohort 1: a first-in-human study to assess the safety and recommended phase II dose of next generation NY-ESO-1-specific TCR T-cells in HLA-A*02 patients with non-small cell lung cancer (DKK 2022)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy expressing an affinity-enhanced T cell receptors (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. This study is recruiting. This substudy will evaluate the safety and efficacy of GSK3901961 in NSCLC.
Clinical • P1 data • P2 data • IO biomarker
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • CTAG2 (Cancer/testis antigen 2)
|
CD8 expression • HLA-A*02 • CTAG1B expression • CTAG2 expression
|
letetresgene autoleucel (GSK3377794) • GSK3901961
2years
Enrollment closed • Combination therapy
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
HLA-A*02:01 • HLA-A*02 • CTAG1B expression • HLA-A2 positive
|
cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
2years
Increased potency and functional persistence in vitro of a next-generation NY-ESO-1-specific TCR therapy incorporating Gen-RTM genetic reprogramming technology (SITC 2022)
Background Letetresgene autoleucel (lete-cel; GSK3377794) is a first-generation (1st gen) NY-ESO-1-specific T-cell receptor (TCR) therapy with demonstrated clinical activity in solid tumors. Conclusions In addition to supporting the hypothesis that genetic reprogramming with Gen-R technology can delay the onset of exhaustion and improve the long-term durable functions of LYL331, these data show that c-Jun overexpression can provide immediate benefits to the NY-ESO-1-specific TCR therapy during primary stimulation in vitro . Based on these promising pre-clinical data, LYL331 may have the potential to improve clinical responses in patients with solid tumor malignancies.
Preclinical • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • CTAG1B (Cancer/testis antigen 1B) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • JUN (Jun proto-oncogene)
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letetresgene autoleucel (GSK3377794) • LYL331
2years
Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma. (PubMed, Nat Commun)
Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. Analysis of tumor samples post-treatment illustrates lete-cel infiltration and a decrease in expression of macrophage genes, suggesting remodeling of the tumor microenvironment. Here we report potential predictive and pharmacodynamic markers of lete-cel response that may inform LDR, cell dose, and strategies to enhance anticancer efficacy.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • CTAG1B (Cancer/testis antigen 1B) • CCR7 (Chemokine (C-C motif) receptor 7) • IL15 (Interleukin 15)
|
letetresgene autoleucel (GSK3377794) • NY-ESO-1 TCR
2years
PROGNOSTIC IMPACT OF NEW YORK ESOPHAGEAL SQUAMOUS CELL CARCINOMA-1 EXPRESSION AND HUMAN LEUKOCYTE ANTIGEN SUBTYPES IN METASTATIC SYNOVIAL SARCOMA (CTOS 2022)
Letetresgene autoleucel (lete-cel), an adoptive T-cell receptor therapy, is currently being investigated in clinical trials in previously treated metastatic SS (mSS) patients (pts) with NY-ESO-1 positive tumors who express at least one of the human leukocyte antigen (HLA) HLA-A*02-01/05/06 (HLA*A) alleles, with encouraging preliminary results... This is the first study to examine the prognostic impact of both NY-ESO-1 and HLA*A type in mSS patients, and the first prognostic study in this population using real-world data and archival tissue. Assessing efficacy of adoptive T-cell therapies in highly selected patients, versus standard treatment through randomized trials, is difficult. In this context, it is essential to ensure that expression of NY-ESO-1 and HLA*A type does not modify the natural history of the disease.Unadjusted results report a longer OS in patients whose tumors express NY-ESO-1, even if the prognostic impact of this antigen disappears in the multivariate analysis.
IO biomarker
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • SSX1 (SSX Family Member 1)
|
HLA-A*02 • CTAG1B expression
|
letetresgene autoleucel (GSK3377794)
over2years
Prevalence and clinical characteristics of metastatic synovial sarcoma (mSS) patients with tumours expressing NY-ESO-1 antigen (NY+) and who are HLA-A*02:01, *02:05 or *02:06 allele positive (HLA+): Cohort study from the French sarcoma group (ESMO 2022)
Background Letetresgene autoleucel is a genetically engineered NY-ESO-1–specific TCR T-cell therapy being investigated in mSS patients whose tumours express the NY-ESO-1 antigen and who are HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06 allele positive (NY+/HLA+)...Conclusions Nationally representative prevalence and clinical profile of mSS patients with NY+/HLA+ tumours were previously unknown and have been documented by this study. Among primary tumour samples, no relationship was observed between NY-ESO expression and age of samples, HLA sub-type, or line of treatment.
Clinical
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
HLA-A*02 • CTAG1B expression
|
letetresgene autoleucel (GSK3377794)
over2years
ZENYTH-ESO: Master protocol to assess the safety and recommended phase II dose of next generation NY-ESO-1-specific TCR T-cells in HLA-A*02 patients with synovial sarcoma and myxoid/round cell liposarcoma [Substudy 3, GSK4427296]. (ASCO 2022)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing an affinity-enhanced T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. Analyses will be descriptive. The master protocol is open for recruitment.
Clinical • P2 data • IO biomarker
|
HLA-A (Major Histocompatibility Complex, Class I, A) • EWSR1 (EWS RNA Binding Protein 1) • CTAG1B (Cancer/testis antigen 1B) • FUS (FUS RNA Binding Protein) • CTAG2 (Cancer/testis antigen 2) • DDIT3 (DNA-damage-inducible transcript 3)
|
HLA-A*02 • CTAG1B expression
|
letetresgene autoleucel (GSK3377794) • LYL132
over2years
ADP-0011-007: Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma (clinicaltrials.gov)
P2, N=23, Completed, GlaxoSmithKline | Active, not recruiting --> Completed | Trial completion date: Aug 2022 --> Mar 2022
Trial completion • Trial completion date
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
HLA-A*02 • CTAG1B expression
|
cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
almost3years
Enrollment closed • Combination therapy
|
PD-L1 (Programmed death ligand 1) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
HLA-A*02
|
Keytruda (pembrolizumab) • letetresgene autoleucel (GSK3377794)
almost3years
Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-β. (PubMed, J Immunol)
We previously generated specific peptide enhanced affinity receptor TCRs recognizing the HLA-A*02-restricted peptides New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/l-Ag family member-1A (TCR: GSK3377794, formerly NY-ESO-1) and melanoma Ag gene A10 (TCR: ADP-A2M10, formerly melanoma Ag gene A10). In this article, we show that exogenous TGF-β inhibited in vitro proliferation and effector functions of human T cells expressing these first-generation high-affinity TCRs, whereas inhibition was reduced or abolished in the case of second-generation TCRs coexpressed with dnTGFβRII (e.g., GSK3845097)...As an example, immunohistochemistry/RNAscope identified TGF-β-positive cells close to T cells in tumor nests and stroma, which had low frequencies of cells expressing IFN-γ in a non-small cell lung cancer setting. Coexpression of dnTGFβRII may therefore improve the efficacy of TCR-transduced T cells.
Journal
|
HLA-A (Major Histocompatibility Complex, Class I, A) • IFNG (Interferon, gamma) • CTAG1B (Cancer/testis antigen 1B) • TGFB1 (Transforming Growth Factor Beta 1)
|
IFNG expression
|
ADP-A2M10 • letetresgene autoleucel (GSK3377794) • GSK3845097
almost3years
IGNYTE-ESO: LETETRESGENE AUTOLEUCEL (LETE-CEL; GSK3377794) SAFETY AND ACTIVITY IN HLA-A*02+ PATIENTS WITH SYNOVIAL SARCOMA OR MYXOID/ROUND CELL LIPOSARCOMA (SUBSTUDIES 1 AND 2): A MASTER PROTOCOL (CTOS 2021)
This study was funded by GSK (208467; NCT03967223). Editorial support was provided by Eithne Maguire, PhD, and Katie Crossland, PhD, of Fishawack Indicia, part of Fishawack Health, UK, and funded by GSK. This abstract was first presented at American Society of Clinical Oncology Annual Meeting on June 4 8, 2021.
Clinical
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
CTAG1B expression
|
letetresgene autoleucel (GSK3377794)
almost3years
SAFETY AND RECOMMENDED PHASE 2 DOSE OF NEXT GENERATION NY-ESO-1-SPECIFIC TCR T-CELLS IN HLA-A*02 PATIENTS WITH SYNOVIAL SARCOMA OR NON-SMALL CELL LUNG CANCER: MASTER PROTOCOL (SUBSTUDIES 1 AND 2) (CTOS 2021)
Objective: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy using a genetically modified T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1/LAGE-1a...Exploratory endpoints include laboratory parameters, overall survival, and anti-GSK3901961 or -GSK3845097 titers as applicable... This study was funded by GSK (209012; NCT04526509). Editorial support was provided by Eithne Maguire, PhD and Katie Crossland, PhD of Fishawack Indicia, part of Fishawack Health, UK; funded by GSK. This abstract was previously presented at the American Association for Cancer Research (April 10–15 and May 17–21, 2021) and the American Society of Clinical Oncology Annual Meeting (June 4–8, 2021).
Clinical • P2 data • IO biomarker
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • TGFB1 (Transforming Growth Factor Beta 1) • CTAG2 (Cancer/testis antigen 2)
|
CD8 expression • CTAG1B expression
|
letetresgene autoleucel (GSK3377794) • GSK3845097 • GSK3901961
almost3years
NY-ESO-1 EXPRESSION PROFILING AND PREVALENCE ASSESSMENT OF TUMOR BIOPSIES FROM PHASE I/II TCR T CELL THERAPY CLINICAL TRIALS IN ADVANCED SYNOVIAL SARCOMA OR MYXOID ROUND CELL LIPOSARCOMA (CTOS 2021)
NY-ESO-1 expression across SS and MRCLS indications express highly similar IHC intensity levels inclusive of 1+, 2+ and 3+ and demonstrated a high prevalence of 71% and 97%, respectively at TPS 1%. As such, NY-ESO-1 strong staining in both SS and MRCLS indications, in a high percentage of patients evaluated supports the tests utility as an aid in the identification of patients who may be eligible for NY-ESO-1 specific T cells (lete-cel) TCR targeted therapy. NY-ESO-1 expression levels and positive prevalence using a clinical trial IHC assay is consistent with what has been reported in the literature (1,2) and demonstrated consistent nuclear and cytoplasmic staining localization in tumor cells in SS and MRCLS sub-types, which are morphologically distinct forms of cancers arising from soft tissues.
Clinical • P1/2 data
|
CTAG1B (Cancer/testis antigen 1B)
|
CTAG1B expression
|
letetresgene autoleucel (GSK3377794)
almost3years
SAFETY AND EFFICACY OF LETETRESGENE AUTOLEUCEL (LETE-CEL; GSK3377794) IN ADVANCED MYXOID/ROUND CELL LIPOSARCOMA (MRCLS) FOLLOWING HIGH LYMPHODEPLETION (COHORT 2): INTERIM ANALYSIS (CTOS 2021)
This open label, pilot study evaluates lete-cel efficacy and safety in advanced MRCLS following low-dose (Cohort 1 [C1]; 30 mg/m2 fludarabine [flu] x 3d + 600 mg/m2 cyclophosphamide [cy] x 3d) or high-dose (Cohort 2 [C2]; 30 mg/ m2 flu x 4d + 900 mg/m2 cy x 3d; initiated based on C1 data) LD. A single lete-cel infusion after high LD showed antitumor activity in advanced MRCLS and a manageable safety profile consistent with other lete-cel studies. The trial is active but no longer recruiting (NCT02992743). MRCLS is included in a separate, ongoing lete-cel study (NCT03967223).
Clinical • IO biomarker
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
CTAG1B expression
|
fludarabine IV • letetresgene autoleucel (GSK3377794)
3years
Safety and Efficacy of Letetresgene Autoleucel (lete-cel; GSK3377794) Alone or in Combination with Pembrolizumab in Relapsed and Refractory Multiple Myeloma (ASH 2021)
A single lete-cel infusion was associated with antitumor activity in 6/6 heavily pretreated RRMM patients, including 1 CR, 1 VGPR, 1PR. Both responses in Arm 2 occurred prior to pembro initiation. The associated safety profile was manageable and consistent with that seen in other lete-cel studies.
Clinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
HLA-A (Major Histocompatibility Complex, Class I, A) • PD-1 (Programmed cell death 1) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
PD-1 expression • CTAG2 expression
|
Keytruda (pembrolizumab) • letetresgene autoleucel (GSK3377794)
3years
Clinical • Trial completion date
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
CTAG1B expression
|
cyclophosphamide • fludarabine IV • letetresgene autoleucel (GSK3377794)
3years
Clinical • IO biomarker
|
CD8 (cluster of differentiation 8) • CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule)
|
CD8 expression
|
letetresgene autoleucel (GSK3377794)
over3years
Clinical • Phase classification
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
CTAG1B expression
|
fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
over3years
[VIRTUAL] A novel, comprehensive glimpse at NY-ESO-1 expression, mRNA to protein translation, & potential impact on clinical studies (ESMO 2021)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) are autologous T cells engineered to express a high affinity TCR capable of recognizing the HLA-A*02:01, *02:05, *02:06 and SLLMWITQC antigen complex... NY-ESO-1 & LAGE-1a were expressed in all indications investigated. NGS was highly correlated to IHC and Sanger sequencing and may be an alternative method for identifying a higher number of tumors that express biomarkers of interest. Our data show a unique platform for comprehensive assessment of disease which may improve patient stratification and management strategies.
Clinical
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
CTAG1B expression • CTAG2 expression
|
letetresgene autoleucel (GSK3377794)
over3years
ADP-0011-007: Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma (clinicaltrials.gov)
P1/2, N=20, Active, not recruiting, GlaxoSmithKline | Recruiting --> Active, not recruiting | Phase classification: P2 --> P1/2
Clinical • Enrollment closed • Phase classification
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B)
|
CTAG1B expression
|
fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
over3years
[VIRTUAL] Master protocol to assess safety and recommended phase 2 dose of next generation NY-ESO-1–specific TCR T-cells in HLA-A*02 patients with synovial sarcoma or non-small cell lung cancer (Substudies 1 and 2). (ASCO 2021)
Clinical Trial Registry Number: NCT04526509 Funding: GlaxoSmithKline (209012) Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy using a genetically modified T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1/LAGE-1a . Exploratory endpoints include laboratory parameters, overall survival, and anti-GSK3901961 or -GSK3845097 titers as applicable . Analyses will be descriptive.
P2 data • Clinical • IO biomarker
|
CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • TGFB1 (Transforming Growth Factor Beta 1) • CTAG2 (Cancer/testis antigen 2)
|
CD8 expression • CTAG1B expression
|
letetresgene autoleucel (GSK3377794) • GSK3845097 • GSK3901961
over3years
[VIRTUAL] Master protocol to assess the safety and recommended Phase 2 dose of next generation NY-ESO-1-specific TCR T-cells in HLA-A*02 patients with synovial sarcoma and non-small cell lung cancer (AACR 2021)
Funding: GSK (209012; NCT04526509) Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing a genetically modified T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. Exploratory endpoints include laboratory parameters, overall survival, and anti-GSK3901961 and anti-GSK3845097 titers for the respective substudies. The substudies are open and recruiting.
Clinical • P2 data
|
CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • TGFB1 (Transforming Growth Factor Beta 1) • CTAG2 (Cancer/testis antigen 2)
|
CD8 expression • CTAG1B expression
|
letetresgene autoleucel (GSK3377794) • GSK3845097 • GSK3901961
over3years
KEYNOTE-487: Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma (clinicaltrials.gov)
P1, N=6, Terminated, GlaxoSmithKline | Phase classification: P2 --> P1 | N=20 --> 6 | Trial completion date: Jan 2023 --> Nov 2020 | Recruiting --> Terminated | Trial primary completion date: Apr 2021 --> Jul 2020; The study was terminated following an internal review of the company's research and development portfolio
Clinical • Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
|
HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
|
Keytruda (pembrolizumab) • fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
almost4years
[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • CTAG2 (Cancer/testis antigen 2)
|
CD8 expression • CTAG1B expression • CTAG2 expression
|
letetresgene autoleucel (GSK3377794) • GSK3901961
almost4years
[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • CTAG2 (Cancer/testis antigen 2)
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CD8 expression • CTAG1B expression • CTAG2 expression
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letetresgene autoleucel (GSK3377794) • GSK3901961
almost4years
[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • CTAG2 (Cancer/testis antigen 2)
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CD8 expression • CTAG1B expression • CTAG2 expression
|
letetresgene autoleucel (GSK3377794) • GSK3901961
almost4years
[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021)
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CTAG1B (Cancer/testis antigen 1B) • CD4 (CD4 Molecule) • CTAG2 (Cancer/testis antigen 2)
|
CD8 expression • CTAG1B expression • CTAG2 expression
|
letetresgene autoleucel (GSK3377794) • GSK3901961
almost4years
Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
P1, N=10, Completed, GlaxoSmithKline | Active, not recruiting --> Completed | Trial completion date: Dec 2021 --> Aug 2020
Clinical • Trial completion • Trial completion date
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG2 (Cancer/testis antigen 2)
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EGFR mutation • ALK rearrangement • CTAG2 expression
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fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
over4years
Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
P1, N=10, Active, not recruiting, GlaxoSmithKline | Trial completion date: Aug 2020 --> Dec 2021
Clinical • Trial completion date
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG2 (Cancer/testis antigen 2)
|
EGFR mutation • ALK rearrangement • CTAG2 expression
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fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
over4years
Clinical • Trial completion date • Trial primary completion date • Combination therapy
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PD-L1 (Programmed death ligand 1) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG1B (Cancer/testis antigen 1B) • CTAG2 (Cancer/testis antigen 2)
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Keytruda (pembrolizumab) • letetresgene autoleucel (GSK3377794)
over4years
[VIRTUAL] OPEN-LABEL PILOT STUDY OF GENETICALLY ENGINEERED NY-ESO-1–SPECIFIC T CELLS (GSK3377794) ALONE OR IN COMBINATION WITH PEMBROLIZUMAB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2020)
Patients in both arms will provide cells via leukapheresis to manufacture autologous NY-ESO-1–specific T cells, undergo lymphodepletion (fludarabine + cyclophosphamide), and then receive GSK3377794 infusion (1−8x109 transduced T cells)...Results - Conclusion As of January 2020, 3 patients have been treated. Funding: GlaxoSmithKline (208470).
Clinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker
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CD38 (CD38 Molecule) • CTAG2 (Cancer/testis antigen 2)
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CD8 expression
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Keytruda (pembrolizumab) • fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
over4years
[VIRTUAL] Open-label pilot study of genetically engineered NY-ESO-1–specific t cells (GSK3377794) alone or in combination with pembrolizumab in relapsed/refractory multiple myeloma. (ASCO 2020)
Patients in both arms will provide cells via leukapheresis to manufacture autologous NY-ESO-1–specific T cells, undergo lymphodepletion (fludarabine + cyclophosphamide), and then receive GSK3377794 infusion (1−8x109 transduced T cells)...As of January 2020, 3 patients have been treated. Funding: GlaxoSmithKline (208470) Research Funding: GlaxoSmithKline
Clinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker
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CD38 (CD38 Molecule) • CTAG2 (Cancer/testis antigen 2)
|
CD8 expression
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Keytruda (pembrolizumab) • fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
almost5years
Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
P1, N=10, Active, not recruiting, GlaxoSmithKline | Trial completion date: Dec 2021 --> Aug 2020
Clinical • Trial completion date
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HLA-A (Major Histocompatibility Complex, Class I, A) • CTAG2 (Cancer/testis antigen 2)
|
EGFR mutation • ALK rearrangement • CTAG2 expression
|
fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous
almost5years
Open-Label Pilot Study of Genetically Engineered NY-ESO-1 Specific T Cells (GSK3377794) Alone or in Combination with Pembrolizumab in Relapsed and Refractory Multiple Myeloma (TCT-ASTCT-CIBMTR 2020)
Each patient will undergo leukapheresis to obtain cells for autologous NY-ESO-1-specific T-cell manufacturing, followed by lymphodepleting chemotherapy with fludarabine + cyclophosphamide, then GSK3377794 infusion of 1−8x109 transduced T cells...A similar presentation will be presented at the ASH Annual Meeting, Orlando, FL, USA, Dec 7-10, 2019. This study (NCT03168438) is funded by GSK.
Clinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker
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CD38 (CD38 Molecule) • CTAG2 (Cancer/testis antigen 2)
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CD8 expression
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Keytruda (pembrolizumab) • fludarabine IV • letetresgene autoleucel (GSK3377794) • cyclophosphamide intravenous