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
- 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.
- 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.