GALLANT-1: Galectin-3 (Gal-3) inhibitor, GB1211, plus atezolizumab (atz) in patients (pts) with non-small cell lung cancer (NSCLC) - a dose finding study followed by a randomised, double-blind, placebo-controlled trial

Gal-3 regulates immune function of T cells and macrophages and promotes neovascularization and fibrosis. Gal-3 is a ligand of LAG-3 and enables signalling in KRAS-mutated tumours. Overexpressed in the tumour microenvironment, Gal-3 has been linked to poor disease outcomes. Gal-3 is a key resistance mechanism for checkpoint inhibitor (CPI) therapies, inhibiting binding of CPIs to their targets; GB1211, a Gal-3 inhibitor, has been shown in non-clinical studies to reverse this inhibition. In retrospective studies, pts with stage IV NSCLC and high Gal-3 levels have been shown to be resistant to pembrolizumab, despite >50% programmed death-ligand 1 (PD-L1) staining (Capalbo 2019), and pts with resected stage II/IIIA NSCLC and high Gal-3 were shown to be resistant to chemotherapy (Kusuhara 2021). In GALLANT-1 (NCT05240131), we will test the hypothesis that Gal-3 inhibition combined with CPI-based immunotherapy may increase response rates in pts with NSCLC, and lead to deeper and longer clinical responses. In a first-in-human study in 78 healthy volunteers (NCT03809052), oral GB1211 was safe and well tolerated as single doses of 5–400 mg and multiple doses of 50 or 100 mg, given twice daily (BID) for 10 days. GB1211 is also being studied in pts with hepatic impairment (NCT05009680). GALLANT-1 is a 3-part phase 1b/2a study that will investigate safety and efficacy of GB1211 + atz vs placebo + atz in pts with advanced or metastatic NSCLC that expresses PD-L1 on ≥50% of tumour cells. Part A (open-label) will assess safety and tolerability of 200 mg and 400 mg GB1211 BID + atz 1200 mg every 3 weeks in 8–12 pts. Primary endpoint is the number of adverse events (AEs) in the 200 mg treatment group compared with the 400 mg group. Part B is a randomised, double-blind study of GB1211 + atz vs placebo + atz, and will enrol 75 pts. Primary endpoints are safety (number of AEs) and efficacy (% change from baseline in the sum of longest diameter of target lesions after 12 weeks’ treatment). Part C is an open-label extension study including pts from Parts A and B, with safety and efficacy assessments. The study has been initiated and is recruiting. NCT05240131. Third-party editorial assistance was provided by Lynda McEvoy, PhD, of Ashfield MedComms, an Ashfield Health company, funded by Galecto Biotech AB. Galecto Biotech AB. This study was sponsored by Galecto Biotech AB. Atezolizumab is manufactured by Roche Registration GmBH.