FDA Grants Breakthrough Therapy Designation to Tiragolumab Combo for PD-L1-High NSCLC

The combination of tiragolumab and atezolizumab (Tecentriq) was granted breakthrough therapy designation based on promising efficacy and safety data observed in the phase 2 CITYSCAPE trial.

The FDA has granted the novel cancer immunotherapy tiragolumab breakthrough therapy designation (BTD) in combination with atezolizumab (Tecentriq) for the first-line treatment of individuals with metastatic non–small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression and no EGFR or ALK genomic tumor aberrations, according to Roche, the developer of the agent.1

The first anti-TIGIT molecule to be granted this designation, tiragolumab was granted BTD based on data from the global, double-blind, randomized phase 2 CITYSCAPE trial (NCT03563716). The study is evaluating tiragolumab plus atezolizumab compared with atezolizumab plus placebo in patients with PD-L1–positive, locally advanced unresectable or metastatic NSCLC in the first-line setting. Patients enrolled onto the study are randomized 1:1 to receive either 600 mg tiragolumab intravenously (IV) plus 1200 mg atezolizumab IV or placebo plus atezolizumab every 3 weeks until disease progression or loss of clinical benefit. The study’s dual primary end points are overall response rate (ORR) and progression-free survival (PFS). Key secondary end points include safety and overall survival.

Thus far, the tiragolumab combination has demonstrated promising efficacy and safety based on trial results that were presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.2

“We have been researching TIGIT as a novel cancer immunotherapy target for almost 10 years and we are pleased that the FDA has acknowledged the potential of tiragolumab to substantially improve outcomes for people with certain types of lung cancer,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a press release. “We look forward to advancing our tiragolumab development program, which includes chemotherapy-free combinations and trials in early stages of disease across multiple cancer types with high unmet need.”

At the primary analysis date of June 30, 2019, the ORR was 31.3% in the tiragolumab arm (95% CI, 19.5%-43.2%) and 16.2% in the placebo arm (95% CI, 6.7%-25.7%), with an odds ratio of 2.57 (95% CI, 1.07-6.14). Moreover, the median PFS was 5.4 months for patients who received tiragolumab plus atezolizumab (95% CI, 4.2-not evaluable) versus 3.6 months for those who received placebo plus atezolizumab (95% CI, 2.7-4.4), with a hazard ratio of 0.57 (95% CI, 0.37-0.90).

Regarding safety, treatment-related adverse events (TRAEs) were reported in 80.6% of those in the tiragolumab arm and in 72.0% in the placebo arm; grade 3 or higher TRAEs occurred in 14.9% and 19.1%, respectively. Further, AEs leading to treatment discontinuation occurred in 7.5% and 10.3%, respectively.

At the new cut-off date of December 2, 2019, investigators found that with an additional 6 months of follow-up (median follow-up of 10.9 months), the improvements observed in ORR and median PFS were maintained for those receiving tiragolumab plus atezolizumab as compared with patients receiving placebo plus atezolizumab. For the tiragolumab arm, the ORR was 37.3% (95% CI, 25.0%-49.6%) and the median PFS was 5.6 months (95% CI, 4.2-10.4) versus 20.6% (95% CI,10.2%-30.9%) and 3.9 months (95% CI, 2.7-4.5), respectively, in the atezolizumab monotherapy arm. The safety profile also remained tolerable.

Of note, an exploratory analysis conducted in individuals with high levels of PD-L1 (tumor proportion score ≥ 50%) demonstrated a clinically meaningful ORR versus atezolizumab plus placebo (66% vs 24%) with a median PFS that was not reached versus 4.11 months with placebo (HR, 0.30; 95% CI, 0.15-0.61).

Roche indicated that biomarker analyses from the CITYSCAPE study will be presented at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer, taking place in January 2021.


1. Roche’s novel anti-TIGIT 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 January 5, 2021. https://www.globenewswire.com/news-release/2021/01/05/2153035/0/en/Roche-s-novel-anti-TIGIT-tiragolumab-granted-FDA-Breakthrough-Therapy-Designation-in-combination-with-Tecentriq-for-PD-L1-high-non-small-cell-lung-cancer.html

2. Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE). J Clin Oncol. 2020;38(suppl 15):9503. doi:10.1200/JCO.2020.38.15_suppl.9503.