WCLC 2025 - Posters & ePosters-P1.11.73 Tiragolumab Plus Atezolizumab and Bevacizumab in Immunotherapy-Refractory, Pd-L1+, Advanced Non-Squamous Non-Small Cell Lung Cancer

P1.11.73 Tiragolumab Plus Atezolizumab and Bevacizumab in Immunotherapy-Refractory, Pd-L1+, Advanced Non-Squamous Non-Small Cell Lung Cancer

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This phase 2, single-arm trial (NCT04958811) investigated the efficacy and safety of combining tiragolumab (anti-TIGIT), atezolizumab (anti-PD-L1), and bevacizumab (anti-VEGF) in patients with advanced, non-squamous non-small cell lung cancer (NSCLC) who were refractory to prior checkpoint inhibitor immunotherapy (CPI) and had PD-L1 positive tumors. Treatments for CPI-refractory NSCLC remain limited, and preclinical evidence suggests that VEGF inhibition and TIGIT blockade can synergize with anti-PD(L)1 therapies to overcome resistance in this setting.<br /><br />The trial enrolled 12 patients with a median age of 63.5 years, majority female and smokers, with PD-L1 expression ≥1%. The primary endpoint was objective response rate (ORR) assessed by RECIST v1.1, using a Simon two-stage design to detect meaningful activity beyond a 4% null ORR.<br /><br />Results showed an ORR of 25% (95% CI: 9.0-53%), with a disease control rate (DCR) of 83% (95% CI: 55-95%). Median progression-free survival (mPFS) was 4.8 months (95% CI: 2.6, not reached), and median overall survival (mOS) was 21.5 months (95% CI: 7.7, not reached). Treatment-emergent adverse events were mainly grade 1-2 and manageable, with grade 3 events including hypertension (17%), colonic perforation (8%), and memory impairment (8%). No grade 4 or 5 treatment-related events were reported.<br /><br />The findings indicate that combining anti-TIGIT, anti-PD-L1, and anti-VEGF therapy presents a promising therapeutic strategy for advanced CPI-refractory NSCLC patients. Ongoing translational studies aim to identify biomarkers predicting benefit, and further trials are warranted to explore this combination's role in overcoming immunotherapy resistance.<br /><br />This study was supported by Georgetown Lombardi Comprehensive Cancer Center, Genentech/Roche, and the LUNGevity Foundation.

Asset Subtitle

Joshua Reuss

Meta Tag

Speaker Joshua Reuss

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

tiragolumab

atezolizumab

bevacizumab

non-small cell lung cancer

NSCLC

checkpoint inhibitor refractory

anti-TIGIT therapy

anti-PD-L1 therapy

anti-VEGF therapy

clinical trial NCT04958811