First-Line Tiragolumab Plus Atezolizumab Yields Survival Benefit in PD-L1–Positive Metastatic NSCLC

The anti-TIGIT therapy tiragolumab administered in combination with atezolizumab showed clinically meaningful improvement at the 2.5-year follow-up vs atezolizumab alone for patients with PD-L1–positive metastatic non–small cell lung cancer.

The immunotherapy combination of tiragolumab plus atezolizumab (Tecentriq) as first-line therapy vs atezolizumab alone showed clinically meaningful results for patients with PD-L1–positive metastatic non–small cell lung cancer (NSCLC), according to 2-year follow-up results from the phase 2 CITYSCAPE trial (NCT03563716) that are set to be presented at the 2021 European Society for Medical Oncology Immuno-Oncology Congress.1

This is the first randomized trial of the anti–T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, or TIGIT, therapy in patients with PD-L1 metastatic NSCLC. The tiragolumab arm resulted in reduction in the risk of progression or death of 38%, with a median progression-free survival (PFS) of 5.6 months compared with 3.9 months for atezolizumab alone (HR, 0.62; 95% CI, 0.42-0.91). Patients also had a better overall response rate (ORR) in the tiragolumab group (38%) vs atezolizumab (20.6%).

“These encouraging results suggest that combining anti-TIGIT and anti–PD-L1 cancer immunotherapies such as tiragolumab and [atezolizumab] could potentially represent a novel approach to address unmet needs in cancer. With tiragolumab, we have the largest and most advanced anti-TIGIT clinical program, and we look forward to the results of our phase 3 trials in lung cancer and other challenging tumor types,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a press release.

This trial enrolled 135 patients, with one group receiving atezolizumab at a fixed dose of 1200 mg administered every 3 weeks by intravenous infusion on day 1 plus a placebo administered intravenously every 3 weeks on day 1. The other group received atezolizumab plus tiragolumab at a fixed dose of 600 mg intravenously every 3 weeks on day 1 of each cycle.

Patients had improved overall survival (OS) with the combination vs single-agent therapy. At the follow-up, OS in the tiragolumab group it was 23.2 months compared with 14.5 months in the atezolizumab group (HR, 0.69; 95% CI, 0.44-1.07). For the exploratory analysis, OS was not reached for the tiragolumab group but investigators have estimated it will be greater than 30.3 months compared with 12.8 months for the atezolizumab group (HR, 0.23; 95% CI, 0.10-0.53).

Additionally, a pre-defined exploratory analysis showed that in the PD-L1–high population (defined as having a tumor proportion score of 50% or greater), there was a 71% reduction in the risk of progression or death. Patients had a median PFS of 16.6 months in the tiragolumab group and 4.1 months in the atezolizumab group (HR, 0.29; 95% CI, 0.15-0.53). Patients in this group also saw improvement in the ORR at 69% in the tiragolumab group and 24.1% in the atezolizumab group.

Grade 3 or 4 treatment-related adverse effects occurred in 22.4% of patients in the tiragolumab group and 25% in the atezolizumab group. The most common all-cause adverse effects were infusion-related reactions, stiffness, dry skin, fatigue, and rash. No new safety signals appeared with longer follow-up, and patient-reported outcomes from the exploratory analysis showed that dyspnea and pain did not interfere with the addition of tiragolumab to atezolizumab.

The FDA had previously granted breakthrough therapy designation to tiragolumab.2 The phase 3 SKYSCRAPER-01 trial (NCT04294810) is currently ongoing and will focus on retaining results in a PD-L1–selected population. 


1. New data from the phase II CITYSCAPE trial show encouraging results with Roche’s novel anti-TIGIT tiragolumab plus Tecentriq. News Release. Roche. December 10, 2021. Accessed December 10, 2021.

2. Roche’s novel antiTIGIT tiragolumab granted FDA breakthrough therapy designation in combination with Tecentriq for PD-L1-high non–small cell lung cancer. News Release. Roche. January 5, 2021. Accessed December 10, 2021.