Pilot Immunotherapy Study With Autologous T-cells Specific for NY-ESO-1/ LAGE-1a-positive Advanced NSCLC Either Alone or in Combination With Pembrolizumab

Official Title

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

Summary:

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-tumour T-cell immune response. New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and cancer testis antigen 2 (LAGE-1a) antigens are tumour-associated proteins that have been found in several tumour 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 tumour targeting T-cells and increases T-cell anti-tumour 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.

Trial Description

Primary Outcome:

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) in participants who received GSK3377794 alone or in combination with pembrolizumab
• Number of participants with adverse events of different severity in participants who received GSK3377794 alone or in combination with pembrolizumab
• Number of participants with AEs and SAEs leading to dose delays
• Number of participants with AEs and SAEs leading to withdrawals
• Number of participants with abnormal findings for hematology parameters
• Number of participants with abnormal findings for clinical chemistry parameters
• Number of participants with abnormal findings for urinalysis parameters
• Number of of participants with abnormal findings for vital signs
• Mean Eastern Cooperative Oncology Group (ECOG) performance status score
• Number of participants with abnormal electrocardiogram (ECG) findings
• Overall response rate (ORR)

• Progression-Free Survival (PFS)
• Disease Control Rate (DCR)
• Duration of Response (DoR)
• Time to Response (TTR)
• Maximum observed concentration (Cmax) following administration of monotherapy of GSK3377794
• Cmax following administration of combination therapy of GSK3377794
• Time to Cmax (Tmax) following administration of monotherapy of GSK3377794
• Tmax following administration of combination therapy of GSK3377794
• Area under the time curve from zero to time t (AUC[0 to t]) following administration of monotherapy of GSK3377794
• AUC(0 to t) following administration of combination therapy of GSK3377794

View this trial on ClinicalTrials.gov