CITYSCAPE trial: promising results adding Tiragolumab to Atezolizumab in patients with PD-L1-positive metastatic non-small cell lung cancer
Results from the phase II CITYSCAPE trial were published. This is the first randomised study evaluating the efficacy and safety of Tiragolumab plus Atezolizumab ( Tecentriq ) compared with Atezolizumab alone as an initial ( first-line ) treatment for people with PD-L1-positive metastatic non-small cell lung cancer ( NSCLC ).
Tiragolumab is a novel cancer immunotherapy designed to bind to TIGIT, an immune checkpoint protein expressed on immune cells.
Both TIGIT and PD-L1 play an important role in immune suppression, and blocking both pathways could enhance anti-tumour activity.
At the primary analysis, Tiragolumab plus Atezolizumab met both co-primary endpoints in the intention-to-treat ( ITT ) population, showing an improvement in the objective response rate ( ORR ) ( 31.3% vs 16.2% ) and a 43% reduction in the risk of disease worsening or death ( progression-free survival; PFS ) ( median PFS= 5.4 vs 3.6 months; hazard ratio, HR=0.57, 95% CI: 0.37–0.90 ) compared with Atezolizumab alone.
An exploratory analysis in people with high levels of PD-L1 ( TPS greater than or equal to 50% ) showed a clinically meaningful improvement in ORR ( 55.2% vs 17.2% ) and a 67% reduction in the risk of disease worsening or death ( median PFS=not reached vs 3.9 months; HR=0.33, 95% CI: 0.15–0.72 ) with the combination compared with Atezolizumab alone.
The data have suggested that the combination of Tiragolumab plus Atezolizumab was well-tolerated, showing similar rates of all grade 3 or more all-cause adverse events when combining the two immunotherapies compared with Atezolizumab alone ( 41.8% vs 44.1% ).
At a six-month follow-up, the improvement in the ORR and PFS in the Tiragolumab plus Atezolizumab arm persisted in both the ITT and the PD-L1-high populations, and no new safety signals were observed.
Tiragolumab is a monoclonal antibody designed to bind with TIGIT, a protein receptor on immune cells. By binding to TIGIT, Tiragolumab blocks its interaction with a protein called poliovirus receptor ( PVR, or CD155 ) that can suppress the body’s immune response.
Blockade of TIGIT and PD-L1 may synergistically enable the re-activation of T-cells and enhance NK cell anti-tumour activity. ( Xagena )
Source: Roche, 2020