Phase 2 Study of the Anti-TIGIT Antibody Tiragolumab plus Atezolizumab versus Placebo plus Atezolizumab as First-Line Treatment in Patients with PD-L1–Selected NSCLC: CITYSCAPE

Tiragolumab (TIRA) is an IgG1/kappa monoclonal antibody that binds T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and prevents interaction with its ligand.¹ In a phase 1 study, it was demonstrated that TIRA alone or in combination with atezolizumab (ATEZO) was safe and effective in treating cancer-immunotherapy-naïve, PD-L1–positive tumors; patients with non–small-cell lung cancer (NSCLC) were included in the study.^1,2

Based on results from that study, the researchers of the phase 2 CITYSCAPE study investigated the efficacy and safety of TIRA plus ATEZO compared with placebo plus ATEZO as first-line therapy of NSCLC.² CITYSCAPE was a prospective, randomized, double-blind trial in patients with locally advanced or metastatic PD-L1–positive NSCLC who had not previously been treated with chemotherapy. The patients (N = 135) were European Cooperative Oncology Group performance status 0-1 and did not have EGFR or ALK mutations.²

Patients were randomized to receive either TIRA 600 mg intravenously (IV) plus ATEZO 1200 mg IV or placebo plus ATEZO 1200 mg IV every 3 weeks.² The patients were stratified by PD-L1 status, tobacco history, and histology.²

The primary end points were objective response rate (ORR) and progression-free survival (PFS).² Overall survival, duration of response, and safety were additional end points. The effects of PD-L1 status on ORR and PFS were exploratory end points.²

At a median follow-up of 5.9 months, TIRA plus ATEZO had improved ORR and median PFS (mPFS) compared with placebo plus ATEZO.² After 6 additional months, improvements in ORR and mPFS were maintained, with an ORR of 37.3% and mPFS of 5.6 months in the TIRA plus ATEZO cohort compared with an ORR of 20.6% and mPFS of 3.9 months in the placebo plus ATEZO cohort.²

Treatment-related adverse events (TRAEs) occurred in 72% of the patients in the placebo plus ATEZO group and in 80.6% in the TIRA plus ATEZO group. Grade ≥3 TRAEs occurred in 19.1% of the patients in the placebo plus ATEZO group and in 14.9% in the TIRA plus ATEZO group. The adverse events that led to withdrawal from treatment occurred in 10.3% of patients in the placebo plus ATEZO group and in 7.5% of patients in the TIRA plus ATEZO group.²

The researchers concluded that therapy with TIRA plus ATEZO demonstrated clinically important improvement in ORR and PFS as first-line treatment in patients with PD-L1–positive NSCLC compared with placebo plus ATEZO.²

References

1. Bendell JC, Bedard P, Bang Y-J, et al. Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors. Presented at: 2020 AACR Virtual Annual Meeting; June 22-24, 2020. Abstract CT302.
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):9503-9503.