Abstract 1192TiP
Background
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).
Trial design
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.
Clinical trial identification
NCT05240131.
Editorial acknowledgement
Third-party editorial assistance was provided by Lynda McEvoy, PhD, of Ashfield MedComms, an Ashfield Health company, funded by Galecto Biotech AB.
Legal entity responsible for the study
Galecto Biotech AB.
Funding
This study was sponsored by Galecto Biotech AB. Atezolizumab is manufactured by Roche Registration GmBH.
Disclosure
F. Ghiringhelli: Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Roche/Genentech. E. Pichon: Financial Interests, Personal, Other, Honoraria: Takeda, Bristol Myers Squibb. S. Ponce Aix: Financial Interests, Personal, Member of the Board of Directors: Oncosur; Financial Interests, Personal, Invited Speaker: Roche, Bristol-Myers Squibb, Merck, Merck Sharp and Dohme, Astra-Zeneca, Targovax, Pfizer, Eli Lilly, PharmaMar, Bayer, Amgen, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Funding: Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Lilly; Financial Interests, Personal, Advisory Role: Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Pfizer, Eli Lilly. O.J. Juan Vidal: Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb, Roche/Genentech, MSD Oncology, AstraZeneca/MedImmune, Takeda; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Lilly, Takeda, AstraZeneca Spain; Financial Interests, Personal, Research Grant: AstraZeneca Spain. E. Carcereny Costa: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Novartis, Roche, Takeda. T. Sethi: Financial Interests, Personal, Full or part-time Employment: Galecto; Financial Interests, Personal, Stocks/Shares: Galecto, AstraZeneca; Financial Interests, Personal, Advisory Role: Galecto, Affibody AB; Financial Interests, Personal, Research Grant: Galecto; Financial Interests, Personal, Royalties: Galecto; Financial Interests, Personal, Expert Testimony: Galecto; Financial Interests, Personal, Other, Travel, Accommodation and Expenses: Galecto. B. Lindmark: Financial Interests, Personal, Leadership Role: ALK-Abelló A/S; Financial Interests, Personal, Stocks/Shares: ALK-Abelló A/S; Financial Interests, Personal, Full or part-time Employment: Galecto. A. MacKinnon: Financial Interests, Personal, Full or part-time Employment: Galeco; Financial Interests, Personal, Stocks/Shares: Galecto. V. Aslanis: Financial Interests, Personal, Full or part-time Employment: Galecto, Inc., Ipsen; Financial Interests, Personal, Stocks/Shares: Galecto, Inc., Ipsen; Financial Interests, Personal, Research Grant: Galecto, Inc., Ipsen; Financial Interests, Personal, Other, Travel/accommodation expenses: Galecto, Inc., Ipsen. D.H. Phung: Financial Interests, Personal, Full or part-time Employment: Galecto; Financial Interests, Personal, Stocks/Shares: Galecto. P. Jensen: Financial Interests, Personal, Full or part-time Employment: Galecto Aps; Financial Interests, Personal, Stocks/Shares: Galecto Aps; Financial Interests, Personal, Project Lead: Galecto Aps. Z. Rajiwate: Financial Interests, Personal, Full or part-time Employment: Pharma Research Associates Limited; Financial Interests, Personal, Stocks/Shares: Galecto. G. Ross: Financial Interests, Personal, Full or part-time Employment: Graham Ross Oncology Consulting Services Ltd; Financial Interests, Personal, Stocks/Shares: Roche-Genentech, GlaxoSmithKline, AstraZeneca; Financial Interests, Personal, Advisory Role, In my capacity as freelance physician: Various; Financial Interests, Personal, Leadership Role, In my capacity as freelance physician: Various. L. Basse: Financial Interests, Personal, Full or part-time Employment: Galecto. All other authors have declared no conflicts of interest.