LUNG CANCER: Early data from an on-going study show the addition of TIGIT blockade to PD-L1 inhibition improves ORR and PFS.
LUNG CANCER; Early data from an on-going study show the addition of TIGIT blockade to PD-L1 inhibition improves ORR and PFS; phase 2 RCT of untreated NSCLC (PD-L1 expression ≥ 1%).
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).
Delvys Rodriguez-Abreu et al ASCO Meeting Library
The immunomodulatory receptor TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers, including NSCLC. In a phase I study (GO30103), co-inhibition of TIGIT and PD-L1 signaling with tira plus atezo in CIT-naïve PD-L1 positive NSCLC potentially improved overall response rates (ORR) compared to historical ORR with PD-L1/PD-1 inhibitors. We conducted this phase II trial to confirm the efficacy and safety of tira plus atezo (TA) compared to placebo plus atezo (PA) in 1L NSCLC (GO40290, NCT NCT03563716).
This prospective, randomized, double-blind, placebo-controlled trial enrolled patients (pts) with chemotherapy-naïve PD-L1+ (TPS ≥ 1% by 22C3 IHC pharmDx Dako assay) locally advanced or metastatic NSCLC with measurable disease, ECOG PS 0-1, and without EGFR or ALK alterations. Pts were randomized 1:1 to TA (tira 600 mg IV plus atezo 1200 mg IV) or PA (placebo plus atezo 1200 mg IV) on day 1 of every 3-week cycle. Stratification factors were PD-L1 status (TPS ≥ 50% vs TPS 1-49%), histology, and tobacco history. Co-primary endpoints were investigator assessed ORR and PFS, and additional endpoints were duration of response (DOR), OS, and safety. Exploratory endpoints were the effect of PD-L1 status on ORR and PFS.
135 pts were randomized to PA (n = 68) or TA (n = 67). At primary analysis (30 Jun 2019), TA improved ORR and median PFS (mPFS) compared to PA, with median follow-up of 5.9 mo. In the safety population (68 in PA, 67 in TA), treatment-related AEs (TRAEs) occurred in 72% (PA) and 80.6% (TA); Grade ≥3 TRAEs occurred in 19.1% (PA) and 14.9% (TA). AEs leading to treatment withdrawal occurred in 10.3% (PA) and 7.5% (TA). Clinical trial information: NCT03563716. With an additional six months of follow-up since the primary analysis (2 Dec 2019, median follow-up of 10.9 mo), improvement in ORR and mPFS was maintained in ITT for TA (37.3% [25.0, 49.6] and 5.6 mo [4.2, 10.4]) vs PA (20.6% [10.2, 30.9] and 3.9 mo [2.7, 4.5]). The safety profile remained tolerable.
Treatment with TA compared to PA showed clinically meaningful improvement in ORR and PFS in ITT. The safety profile of TA was similar to PA.