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Report for Clinical Trial NCT03709706

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

Adoptive T-cell therapy (ACT) is a therapeutic approach that uses T lymphocytes of participants with cancer, obtained by leukapheresis with the aim of generating an anti-tumor T-cell immune response. New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and cancer testis antigen 2 (LAGE-1a) antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using ACT with T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses in participants with cancer. Pembrolizumab is a monoclonal antibody that acts specifically on tumor targeting T-cells and increases T-cell anti-tumor function. Pembrolizumab will be used in combination with NY-ESO-1/LAGE-1a T Cell Receptors (TCR) engineered participant T-cells (GSK3377794) to potentially further improve therapy for participants. The primary objective of the study is to evaluate the safety and tolerability of autologous genetically modified T-cells (GSK3377794) in human leukocyte antigen (HLA) positive participants with NY-ES0-1/ LAGE-1a positive advanced non-small cell lung cancer (NSCLC) alone (Arm A) or GSK3377794 in combination with pembrolizumab in participants with NSCLC with wildtype epidermal growth factor receptor (WT EGFR) and WT anaplastic lymphoma kinase/ c-ros oncogene 1 (ALK/ROS1) (Arm B) and participants with NSCLC with EGFR or ALK/ROS1 aberration (Arm C). This study consists of screening phase, Leukapheresis/ GSK3377794 manufacture, lymphodepletion/treatment phase and follow-up. Participants will receive GSK3377794 as monotherapy (Arm A); or as a combination therapy with pembrolizumab (Arm B), and participants in Arm C will receive the same treatment as participants in the Arm B. Approximately 54 participants will be enrolled into the study.

NCT03709706 Neoplasms

2 Interventions

Name: GSK3377794

Description: GSK3377794 will be given as a single IV infusion of 1 to 8 x10^9 transduced cells.
Type: Drug
Group Labels: 3

Arm A: Participants receiving GSK3377794 monotherapy Arm B: Participants receiving GSK3377794 plus pembrolizumab Arm C: Participants receiving GSK3377794 with pembrolizumab

Name: Pembrolizumab

Description: Pembrolizumab will be given as a dose of 200 milligrams using a 30-minute IV infusion.
Type: Drug
Group Labels: 2

Arm B: Participants receiving GSK3377794 plus pembrolizumab Arm C: Participants receiving GSK3377794 with pembrolizumab


Primary Outcomes

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment.

Measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs) in participants who received GSK3377794 alone or in combination with pembrolizumab

Time: Up to 106 weeks

Description: The severity of AEs will be graded according to National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE) version 4.03.

Measure: Number of participants with adverse events of different severity in participants who received GSK3377794 alone or in combination with pembrolizumab

Time: Up to 106 weeks

Description: Number of participants with AEs and SAEs leading to dose delays will be reported.

Measure: Number of participants with AEs and SAEs leading to dose delays

Time: Up to 106 weeks

Description: Number of participants with AEs and SAEs leading to withdrawals will be reported.

Measure: Number of participants with AEs and SAEs leading to withdrawals

Time: Up to 106 weeks

Description: Blood samples will be collected for analysis of hematology parameters including platelet counts, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell count (RBC), hemoglobin and hematocrit.

Measure: Number of participants with abnormal findings for hematology parameters

Time: Up to 106 weeks

Description: Blood samples will be collected for analysis of clinical chemistry parameters including blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total and direct bilirubin, creatinine, sodium, alanine aminotransferase (ALT), total protein, glucose, calcium, alkaline phosphatase, chloride, albumin, phosphorus, low density lipid (LDH), urea, potassium, magnesium and bicarbonate.

Measure: Number of participants with abnormal findings for clinical chemistry parameters

Time: Up to 106 weeks

Description: Urine samples will be collected for the analysis of the following urine parameters: specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite and leukocyte esterase by dipstick.

Measure: Number of participants with abnormal findings for urinalysis parameters

Time: Up to 106 weeks

Description: Vital sign parameters including systolic and diastolic blood pressure, respiratory rate, pulse rate, and temperature will be assessed.

Measure: Number of of participants with abnormal findings for vital signs

Time: Up to 106 weeks

Description: ECOG performance status is a measure of the participant's ability to carry out activities of daily living on a 6-point scale ranging from 0 (fully active) to 5 (Dead).

Measure: Mean Eastern Cooperative Oncology Group (ECOG) performance status score

Time: Up to 106 weeks

Description: Twelve-lead ECG will be obtained using an ECG machine.

Measure: Number of participants with abnormal electrocardiogram (ECG) findings

Time: Up to 106 weeks

Description: ORR is the percentage of participants with a confirmed complete response (CR) or a partial response (PR) at any time as per Response evaluation criteria in solid tumors (RECIST) version 1.1 as determined by the local investigators.

Measure: Overall response rate (ORR)

Time: Up to 106 weeks

Secondary Outcomes

Description: PFS is defined as the time from the date of T-cell infusion until the earliest date of disease progression as per RECIST version 1.1 as determined by the local investigators, or death due to any cause.

Measure: Progression-Free Survival (PFS)

Time: Up to 106 weeks

Description: DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) for at least 6 months as per RECIST version 1.1 as determined by the local investigators.

Measure: Disease Control Rate (DCR)

Time: Up to 106 weeks

Description: DoR is defined as, in the subset of participants who show a confirmed CR or PR as determined by the local investigators, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

Measure: Duration of Response (DoR)

Time: Up to 106 weeks

Description: TTR is the time from the date of T-cell infusion to the first documented evidence of response (PR or better) in the subset of participants who achieved a confirmed PR or CR as determined by the local investigators.

Measure: Time to Response (TTR)

Time: Up to 106 weeks

Description: Blood samples will be collected for pharmacokinetic analysis.

Measure: Maximum observed concentration (Cmax) following administration of monotherapy of GSK3377794

Time: Up to 106 weeks post-dose

Description: Blood samples will be collected for pharmacokinetic analysis.

Measure: Cmax following administration of combination therapy of GSK3377794

Time: Up to 106 weeks post-dose

Description: Blood samples will be collected for pharmacokinetic analysis

Measure: Time to Cmax (Tmax) following administration of monotherapy of GSK3377794

Time: Up to 106 weeks post-dose

Description: Blood samples will be collected for pharmacokinetic analysis.

Measure: Tmax following administration of combination therapy of GSK3377794

Time: Up to 106 weeks post-dose

Description: Blood samples will be collected for pharmacokinetic analysis.

Measure: Area under the time curve from zero to time t (AUC[0 to t]) following administration of monotherapy of GSK3377794

Time: Up to 106 weeks post-dose

Description: Blood samples will be collected for pharmacokinetic analysis.

Measure: AUC(0 to t) following administration of combination therapy of GSK3377794

Time: Up to 106 weeks post-dose

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

Exclusion Criteria: For Screening (Part 1): - NSCLC with B-Raf gene (BRAF) V600E mutation, Neurotrophic Tropomyosin-Related Kinase (NTRK) gene fusion, and/or any other actionable genetic aberration that can be treated with targeted SoC (NCCN recommended) therapy. --- V600E ---



HPO Nodes