GSK208471: A Phase 1b/2a Pilot Randomized 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

GSK208471: A Phase 1b/2a Pilot Randomized 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

Gender
Minimum Age
Maximum Age
Adults
Physicians
Owonikoko, Taofeek
Phases
II
Drugs
Pembrolizumab (1307) GSK3377794 (1603)
Disease Sites
Lung
Locations
Winship Cancer Institute of Emory University Winship at Emory University Hospital Midtown
NCT ID
NCT03709706
Protocol Number
GSK208471
Contact
If interested in learning more about this clinical trial, please contact winshipcto@emory.edu or (404) 778-1868.

Title

GSK208471: A Phase 1b/2a Pilot Randomized 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

Primary Objective:

  • To evaluate the safety and tolerability of autologous genetically modified T-cells (GSK3377794) in human leukocyte antigen (HLA) HLA-A02:01, HLA-A02:05 and/or HLA-A*02:06 positive participants with NY-ESO-1 and/or LAGE-1a positive advanced NSCLC alone [Arm A] or GSK3377794 in combination with pembrolizumab in participants with NSCLC with WT EGFR and WT ALK/ROS1 [Arm B]and participants with NSCLC with EGFR or ALK/ROS1 aberration [Arm C]

Secondary Objectives:

  • To further investigate the anti-tumor activity of GSK3377794.

  • To describe the persistence of GSK3377794 overtime.

Exploratory Objectives:

  • To evaluate survival.

  • To Assess correlation of T-cell persistence with safety, clinical response, and phenotype of infused T-cells.

  • Correlation assessed by regression analysis and/or other statistical methods

  • To explore mechanisms of clinical benefit TCR diversity, immune cell subsets in blood and tumor based on PD-L1, NYESO-1/LAGE-1a, tumor mutation burden (TMB), gene expression profile, and other biomarkers.

  • To explore the relationship between antigen expression and treatment response.

  • To determine levels of NY-ESO-1/LAGE-1a antigen by RNA and protein analysis and evaluate the relationship of antigen to response.

  • To explore potential immune response to GSK3377794.

  • To determine presence and titers of anti- GSK3377794 antibodies over time.

  • To evaluate the quality of life and daily functioning of participants receiving GSK3377794 PRO-CTCAE EORTC-QLQ-C30 and EORTC-QLQLC13 FACT-GP5

Detail

Primary Objective:

  • To evaluate the safety and tolerability of autologous genetically modified T-cells (GSK3377794) in human leukocyte antigen (HLA) HLA-A02:01, HLA-A02:05 and/or HLA-A*02:06 positive participants with NY-ESO-1 and/or LAGE-1a positive advanced NSCLC alone [Arm A] or GSK3377794 in combination with pembrolizumab in participants with NSCLC with WT EGFR and WT ALK/ROS1 [Arm B]and participants with NSCLC with EGFR or ALK/ROS1 aberration [Arm C]

Secondary Objectives:

  • To further investigate the anti-tumor activity of GSK3377794.

  • To describe the persistence of GSK3377794 overtime.

Exploratory Objectives:

  • To evaluate survival.

  • To Assess correlation of T-cell persistence with safety, clinical response, and phenotype of infused T-cells.

  • Correlation assessed by regression analysis and/or other statistical methods

  • To explore mechanisms of clinical benefit TCR diversity, immune cell subsets in blood and tumor based on PD-L1, NYESO-1/LAGE-1a, tumor mutation burden (TMB), gene expression profile, and other biomarkers.

  • To explore the relationship between antigen expression and treatment response.

  • To determine levels of NY-ESO-1/LAGE-1a antigen by RNA and protein analysis and evaluate the relationship of antigen to response.

  • To explore potential immune response to GSK3377794.

  • To determine presence and titers of anti- GSK3377794 antibodies over time.

  • To evaluate the quality of life and daily functioning of participants receiving GSK3377794 PRO-CTCAE EORTC-QLQ-C30 and EORTC-QLQLC13 FACT-GP5

Eligibility