Results from the MORPHEUS-liver study: Phase Ib/II randomized evaluation of tiragolumab (tira) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC).
Richard S. Finn, Baek‐Yeol Ryoo, Chih‐Hung Hsu, Daneng Li, Adam Burgoyne, Christopher Cotter, Shreya Badhrinarayanan, Yulei Wang, Anqi Yin, Tirupathi Rao Edubilli, Edward Gane
Abstract
4010 Background: Atezo + bev is the current first-line standard of care for uHCC based on the IMbrave150 study, which demonstrated superior overall survival, progression-free survival (PFS), and objective response rate (ORR) vs sorafenib (Finn, et al. New Engl J Med 2020; Cheng, et al. J Hepatol 2022). TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells. Tira (anti-TIGIT) may synergize with other immunotherapies, such as PD-L1/PD-1 inhibitors. The MORPHEUS platform comprises multiple phase Ib/II trials to identify early efficacy signals and safety of treatment combinations across cancers. Here we report data from a cohort of the MORPHEUS-liver study (NCT04524871) evaluating the combination of tira + atezo + bev vs a control arm (atezo + bev) in patients with uHCC. Methods: Patients with previously untreated uHCC were randomized to receive atezo (1200mg IV) + bev (15mg/kg IV) with or without tira (600mg IV) every three weeks. The primary endpoint was investigator-assessed ORR by RECIST V1.1. Secondary endpoints included PFS and safety. Results: A total of 58 patients were randomized (tira + atezo + bev, n=40; atezo + bev, n=18). As of 28 November 2022, median follow up was 14.0 months in the tira + atezo + bev arm and 11.8 months in the control arm. Confirmed ORR was higher in the tira + atezo + bev arm (42.5%) vs the control arm (11.1%). Median PFS was longer with tira + atezo + bev (11.1 months; 95% CI: 8.2–NE) vs control (4.2 months; 95% CI: 1.6–7.4), corresponding to a PFS hazard ratio (HR) of 0.42 (95% CI: 0.22–0.82). A similar pattern of increased ORR and PFS was observed for the treatment arms in both PD-L1+ (n=23) and PD-L1– (n=27) subgroups. For tira + atezo + bev vs control arm, grade 3/4 treatment-related AEs were 27.5% vs 33.3% and AEs leading to any treatment discontinuation were 22.5% vs 22.2%, respectively. Conclusions: The addition of tira to atezo + bev resulted in higher ORR and longer PFS compared with atezo + bev, and no new safety signals were identified. These data suggest that tira + atezo + bev may be a promising novel first-line treatment option for patients with uHCC, and support further study in this setting. Clinical trial information: NCT04524871 . [Table: see text]