Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Recurrence

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Lung Neoplasms

Esophageal Squamous Cell Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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

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

lete-cel will be administered to eligible participants.

Lete-cel

Pembrolizumab will be administered to eligible participants.

GSK Clinical Trials

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

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.

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

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

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

IPD for this study will be made available via the Clinical Study Data Request site.

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.

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.

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.

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.

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.

Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by investigator per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.

DCR was defined as the percentage of participants with a confirmed complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months as per RECIST v1.1. 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). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.

Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. 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.

Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. 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 mm.

Cmax was defined as peak cell expansion during the study. Blood samples were collected for analysis of Cmax of lete-cel.

Tmax was defined as time to reach peak cell expansion during the study. Blood samples were collected for analysis of Tmax of lete-cel.

Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days).

Merck Sharp & Dohme LLC

GlaxoSmithKline

All cause mortality , SAEs and non-serious adverse events were reported for the Intent to Treat (ITT) population that includes all participants who started the leukapheresis procedure. Participants in the "No Treatment" arm started the leukapheresis procedure but did not receive lymphodepletion chemotherapy or Lete-cel infusion.

Eligible participants underwent leukapheresis to manufacture autologous T cells bearing T- cell receptors (TCR) specific for NY-ESO-1/LAGE-1a. Lymphodepleting chemotherapy was administered, consisting of cyclophosphamide at a dose of 900 mg/m\^2/day on day -7 through day -5 and fludarabine at a dose of 30 mg/m\^2/day on day -8 through day -5. On day 1, participants received a single infusion of Lete-cel. Participants who had disease progression within 25 weeks of Lete-cel infusion were offered therapy with Pembrolizumab following benefit-risk evaluation. Pembrolizumab 200 mg was administered every three weeks (Q3W) for up to 35 cycles (up to Week 106) or until subsequent disease progression or intolerable toxicity. Pembrolizumab therapy was not allowed if disease progression occurred post 25 weeks of Lete-cel infusion.

Arm A: Lete-cel Monotherapy

Eligible participants underwent leukapheresis to manufacture autologous T cells bearing T-cell receptors (TCR) specific for NY-ESO-1 /LAGE-1a. Lymphodepleting chemotherapy was administered, consisting of cyclophosphamide at a dose of 900 mg/m\^2/day on day -7 through day -5 and fludarabine at a dose of 30 mg/m\^2/day on day -8 through day -5. On day 1, participants received a single infusion of Lete-cel followed by pembrolizumab 200 mg starting on Day 22 (Week 4 Day 1). Pembrolizumab was administered every three weeks (Q3W) for up to 35 cycles (up to Week 106) or until disease progression, whichever occurred first.

Arm C: Lete-cel + Pembrolizumab

Participants who underwent leukapheresis but did not go on to receive lymphodepletion chemotherapy or T-cell infusion.

No Treatment

Total

Age, Continuous

Sex: Female, Male

Asian

White

Unknown or Not Reported

Race/Ethnicity, Customized

GSK Response Center

SAEs

Modified Intent-to-Treat (mITT) population included all participants who received Lete-cel infusion.

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

Modified Intent to Treat (mITT) population.

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

AEs, Grade 2

AEs, Grade 3

AEs, Grade 4

AEs, Grade 5

SAEs, Grade 3

SAEs, Grade 4

SAEs, Grade 5

Modified intent-to-treat (mITT) population

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

Number of Participants With AEs Leading to Dose Delays

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

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

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

Modified intent-to-treat (mITT) population. Only participants with CR or PR were included in the analysis. No participant achieved CR or PR, hence the number of participants analyzed is 0.

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

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

Pharmacokinetic (PK) population included all participants in the mITT population from whom at least one PK sample was obtained, analyzed, and was measurable.

Spots Global Cancer Trial Database for t cell receptors