1460P GALLANT-1: GB1211 galectin-3 (Gal-3) inhibitor plus atezolizumab (atz) for first line treatment in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC)

Gal-3 expression in tumours is associated with resistance to checkpoint inhibitors (CPIs). In a preclinical study, Gal-3 inhibitor GB1211 restored CPI-binding to their targets in the presence of Gal-3 (Mabbitt et al. J Clin Oncol 2022 ), and enhanced CPI effects in NSCLC mouse models (Vuong et al. Cancer Res. 2019). The GALLANT-1 study (NCT05240131) will assess whether GB1211 + atz (a CPI) increases anti-tumour effects in pts with NSCLC. GALLANT-1 is a phase IB/IIA study of first line GB1211 + atz in pts with advanced/metastatic NSCLC. Part A is an open-label dose confirmation study of GB1211 200 mg or 100 mg twice daily (BID) + atz 1200 mg every 3 weeks; Part B is a 12-week, randomized double-blind study of the safety and efficacy of the GB1211 dose from Part A + atz vs placebo + atz. Following Part B, pts will continue into an open-label extension study until disease progression or unacceptable toxicity occur. Here we report data from the ongoing Part A. In the 200 mg cohort (n = 7), all pts had an adverse event (AE); most were mild (Grade [Gr] 1–2) and no serious AEs were deemed related to GB1211 alone. After 2 weeks of therapy, 2 severe (Gr 3–4) autoimmune skin rashes were observed: pemphigus deemed related to atz, and perivascular lymphocytic infiltration deemed related to GB1211 + atz; both responded to steroids. As per protocol, it was recommended that the study continue but with a reduced dose (100 mg BID) in new pts (n = 2); 9 AEs (all Gr 1–2) were reported in these 2 pts. Two partial responses, as assessed by investigators, have been seen: 1 confirmed (100 mg cohort; Week 6; time on therapy: 14 weeks) and 1 awaiting confirmation (200 mg cohort; Week 18; time on therapy: 23 weeks). Steady-state plasma exposure at 200 mg was consistent with pharmacokinetic (PK) simulations, predicting a 2-fold increase compared with healthy volunteers at 100 mg. GB1211 PK did not seem altered in pts with NSCLC vs healthy volunteers. This is the first clinical study to show that combining GB1211 with atz may enhance the CPI effect. As the AEs have been manageable, Part A will continue with the 100 mg GB1211 dose to confirm the selected dose for Part B.