Dr Melissa Johnson: Tiragolumab Plus Atezolizumab Improves Objective Response in CITYSCAPE Trial

June 1, 2020

Blocking TIGIT, a T-cell immunoreceptor, benefits patients with non–small lung cancer in that it can restore their immune system’s antitumor response, leading to a greater objective response and progression-free survival, noted Melissa L. Johnson, MD, associate director for Lung Cancer Research at Sarah Cannon Research Institute and partner in Tennessee Oncology, discussing the results of the CITYSCAPE trial.

Blocking TIGIT, a T-cell immunoreceptor, benefits patients with non—small lung cancer in that it can restore their immune system’s antitumor response, leading to a greater objective response and progression-free survival, noted Melissa L. Johnson, MD, associate director for Lung Cancer Research at Sarah Cannon Research Institute and partner in Tennessee Oncology, discussing the results of the CITYSCAPE trial.

Transcript:

At ASCO this year, you are presenting on the CITYSCAPE trial. Can you provide some background on the trial, as well as its notable results?

CITYSCAPE is a randomized phase 2 trial. We enrolled 135 patients. Patients were newly diagnosed with metastatic non—small cell lung cancer. They were negative for EGFR and ALK alterations, and their tumors expressed PD-L1 at least 1% or higher as tested using the Dako 22C3 assay. That assay could be done locally or centrally. Patients were randomized to receive tiragolumab, an anti-TIGIT antibody, plus atezolizumab, a PD-L1 antibody versus placebo plus atezolizumab. The primary endpoints were objective response rate and PFS. And the trial showed that patients that received the combination, tira plus atezo, had improved objective response as well as PFS compared to patients that were treated with placebo plus atezolizumab.

What is the particular mechanism of action of the anti-TIGIT immunotherapy that is important in the lung cancer space?

TIGIT is another inhibitory checkpoint. It works similarly to PD-L1. TIGIT is expressed on immune cells, T cells, and natural killer cells, and when it binds to its ligand, PVR, on tumor cells or antigen-presenting cells, it can blunt the immune response. So in a similar way to blocking PD-1 or PD-L1, when you block TIGIT with the anti-TIGIT antibody, tiragolumab, you can restore the antitumor immune response and activate inflammatory cells to fight the cancer.