In a phase II trial (CITYSCAPE) reported in The Lancet Oncology, Byoung Chul Cho, MD, and colleagues found that the addition of tiragolumab, an inhibitor of the immune checkpoint molecule TIGIT, to atezolizumab improved objective response rate and progression-free survival in first-line treatment of patients with PD-L1–positive recurrent or metastatic non–small cell lung cancer (NSCLC).

Byoung Chul Cho, MD

Study Details

In the double-blind trial, 135 patients with measureable disease and no EGFR or ALK alterations from sites in Europe, Asia, and the United States were randomly assigned between August 2018 and March 2019 to receive tiragolumab at 600 mg plus atezolizumab at 1,200 mg (n = 67) or placebo plus atezolizumab every 3 weeks. PD-L1 positivity was defined as a tumor proportion score of ≥ 1%. The coprimary endpoints were investigator-assessed objective response rate and progression-free survival.

Response Rate and Progression-Free Survival

At the time of primary analysis (in June 2019), median follow-up was 5.9 months (interquartile range = 4.6–7.6 months). Objective response was observed in 21 patients (31.3%, 95% confidence interval [CI] = 19.5%–43.2%) in the tiragolumab/atezolizumab group vs 11 patients (16.2%, 95% CI = 6.7%–25.7%) in the control group (P = .031). Duration of response data were not mature. Median progression-free survival was 5.4 months (95% CI = 4.2 months–not estimable) in the tiragolumab/atezolizumab group vs 3.6 months (95% CI = 2.7–4.4 months) in the control group (stratified hazard ratio [HR] = 0.57, 95% CI = 0.37–0.90, P = .015).

In an unplanned updated analysis (in August 2021), median follow-up was 30.4 months. Median duration of response was 17.6 months (95% CI = 9.1–26.1 months) in the tiragolumab/atezolizumab group responders vs 10.7 months (95% CI = 6.0–18.8 months) in the control group responders. Median progression-free survival was 5.6 months (95% CI = 4.2–10.4 months) vs 3.9 months (95% CI = 2.7–4.5; HR = 0.62, 95% CI = 0.42–0.91, P = .013). Median overall survival was 23.2 months (95% CI = 14.1–31.5 months) vs 14.5 months (95% CI = 9.6–20.4 months; HR = 0.69, 95% CI = 0.44–1.07, P = .093).   

Adverse Events

The most common treatment-related grade ≥ 3 adverse events in the tiragolumab/atezolizumab group were increased lipase (9% vs 3% in control group) and diabetes (3% vs 1%) Treatment-related serious adverse events occurred in 21% vs 18% of patients. Adverse events led to discontinuation of treatment in 15% vs 13%. Immune-mediated adverse events, primarily grade 1 and 2, occurred in 76% vs 47% of patients. Two treatment-related deaths, due to pyrexia and infection, occurred in the tiragolumab/atezolizumab group.

The investigators concluded, “Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1–positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC.”

Dr. Cho, of Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by F. Hoffmann-La Roche and Genentech. For full disclosures of the study authors, visit thelancet.com.