CITYSCAPE: Tiragolumab plus atezolizumab for non-small cell lung cancer

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Published: 17 Jun 2020
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Dr Melissa Johnson - Sarah Cannon Research Institute, Nashville, USA

Dr Melissa Johnson speaks to ecancer in an online interview for the virtual ASCO 2020 meeting.

The CITYSCAPE trial is a randomised, double-blind, phase II study of the anti-TIGIT antibody tiragolumab atezolizumab vs placebo atezolizumab in patients with PD-L1-selected NSCLC.

Dr Johnson outlines the trial design, promising results and future prospects of the CITYSCAPE study.

This programme has been supported by an unrestricted educational grant from Bristol Myers Squibb.

I’m going to tell you about the CITYSCAPE trial which was a randomised phase II trial for patients with newly diagnosed non-small cell lung cancer. Tiragolumab is an anti-TIGIT antibody. TIGIT is an inhibitory checkpoint; it’s expressed on tumour infiltrating T-cells and natural killer cells and, like PD-L1, can be inhibited in such a way that restores anti-tumour immunity.

Patients in the trial received tiragolumab and atezolizumab versus atezolizumab and placebo. 140 newly diagnosed non-small cell lung cancer patients were enrolled. All patients had PD-L1 testing performed using the Dako 22C3 assay. The PD-L1 assay could be done locally or centrally. Patients were randomised to receive combination immunotherapy or atezolizumab and placebo alone. The primary endpoints were objective response rate and PFS.

The patients that were treated in the combination arm to receive triagolumab and atezolizumab versus atezolizumab and placebo had improved objective response rate and PFS as compared to patients that were treated with atezolizumab alone. Probably even more importantly, patients tolerated the combination of tiragolumab and atezolizumab about as well as they did atezolizumab alone. The most common side effects that were reported on the trial were infusion reactions, most common with the first dose, as well as some rash and pruritis. There was a slight increase in the immune mediated adverse events among patients who received tiragolumab and atezolizumab versus atezolizumab alone. Interestingly, patients whose tumours expressed high levels of PD-L1 had an objective response of 66% versus 24% with atezolizumab alone. Likewise, their progression free was not reached versus patients treated with atezolizumab alone.

So in this small randomised phase II trial we see a suggestion that the two drugs together, tiragolumab and atezolizumab, may be more efficacious than atezolizumab alone. This is exciting and at ASCO where we also had other reports of other immune combinations, nivolumab ipilimumab, for example, nivolumab ipilimumab chemo in CheckMate-227 as well as 9LA. Notably, in the CITYSCAPE data the rates of discontinuation due to treatment related adverse events were similar between the two arms, around 10%, which was less than in the trials in which patients were treated with immune combination nivolumab ipilimumab.

So this was a small effort and it has led to a randomised phase III trial that’s now enrolling. We are eager to see if tiragolumab atezolizumab may be another chemotherapy free regimen for the treatment of newly diagnosed non-small cell lung cancer patients.