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)

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT05240131.

Editorial acknowledgement

Third-party medical writing assistance was provided by Roisin Weaver MSc, of Ashfield MedComms, an Inizio company, and was funded by Galecto Biotech AB.

Legal entity responsible for the study

Galecto Biotech AB.

Funding

Galecto Biotech AB.

Disclosure

F.D.A. Aparisi Aparisi: Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. E. Pichon: Financial Interests, Institutional, Funding: BeiGene, Bristol Myers Squibb, MSD, Janssen, AstraZeneca; Financial Interests, Institutional, Other, Honoraria: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses, Honoraria: Takeda; Financial Interests, Personal, Advisory Board: Takeda. E. Carcereny: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Research Grant: Merk. R. Raumlau: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis, Takeda, Parexel; Financial Interests, Personal, Invited Speaker: Roche, Boehringer Ingelheim, Novartis, Pfizer, Amgen, BMS, MSD, Merck, AstraZeneca, Parexel, Bioatla Inc, Janssen-Cilag, AstraZeneca, Maia Biothechnology, Cantargia AB, Shanghai Henlius Biotech, BioNtech SE, Arcus Biosciences Inc. T. Sethi: Financial Interests, Personal, Stocks/Shares: Galecto Biotech, AstraZeneca; Financial Interests, Personal, Expert Testimony: Galecto Biotech; Financial Interests, Personal, Royalties: Galecto Biotech; Financial Interests, Personal, Advisory Role: Galecto Biotech; Financial Interests, Personal, Full or part-time Employment: Galecto Biotech; Financial Interests, Personal, Other, Patents, other intellectual property: Galecto Biotech; Non-Financial Interests, Personal, Advisory Role: Affibody. B. Lindmark: Financial Interests, Personal, Stocks/Shares: Galecto Biotech, ALK-Abello, Aqilion AB; Financial Interests, Personal, Officer: Galecto Biotech; Financial Interests, Personal, Full or part-time Employment: Galecto Biotech; Financial Interests, Personal, Member of Board of Directors: ALK-Abello, Aqilion AB; Financial Interests, Personal, Leadership Role: ALK-Abello. R. Slack: Financial Interests, Institutional, Stocks/Shares: Galecto Biotech; Financial Interests, Institutional, Full or part-time Employment: Galecto Biotech; Financial Interests, Personal, Stocks/Shares: GSK. A. MacKinnon: Financial Interests, Personal and Institutional, Stocks/Shares: Galecto Biotech; Financial Interests, Personal and Institutional, Expert Testimony: Galecto Biotech; Financial Interests, Personal and Institutional, Royalties: Galecto Biotech; Financial Interests, Personal and Institutional, Funding: Galecto Biotech; Financial Interests, Personal and Institutional, Full or part-time Employment: Galecto Biotech; Financial Interests, Personal and Institutional, Other, Patents, other intellectual property: Galecto Biotech. V. Aslanis: Financial Interests, Personal, Stocks/Shares: Galecto Biotech; Financial Interests, Personal, Funding: Galecto Biotech; Financial Interests, Personal, Full or part-time Employment: Galecto Biotech. D. Phung: Financial Interests, Personal, Stocks/Shares: Galecto Biotech; Financial Interests, Personal, Advisory Role: Galecto Biotech; Financial Interests, Personal, Full or part-time Employment: Galecto Biotech. P. Jensen: Financial Interests, Institutional, Stocks/Shares: Galecto Biotech; Financial Interests, Institutional, Advisory Role: Galecto Biotech; Financial Interests, Institutional, Full or part-time Employment: Galecto Biotech; Financial Interests, Institutional, Other, Travel, accommodation, expenses: Galecto Biotech. Z. Rajiwate: Financial Interests, Personal, Stocks/Shares: Galecto Biotech; Financial Interests, Personal, Full or part-time Employment: Galecto Biotech; Financial Interests, Personal, Other, Travel, accommodations, expenses: Galecto Biotech. G. Ross: Financial Interests, Institutional, Full or part-time Employment: Galecto Biotech; Financial Interests, Personal, Stocks/Shares: Roche/Genentech, GSK, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: Graham Ross Oncology Consulting Services Ltd, Various (in my capacity as freelance physician); Financial Interests, Personal, Advisory Role: Various (in my capacity as freelance physician); Financial Interests, Personal, Leadership Role: Various (in my capacity as freelance physician); Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Various (in my capacity as freelance physician). L. Basse: Financial Interests, Personal, Full or part-time Employment: Galecto Biotech; Financial Interests, Personal, Stocks/Shares: Genmab, NovoNordisk, Lava Therapeutics, Ambu, BioNTech; Financial Interests, Personal, Advisory Role: Ambu; Financial Interests, Personal and Institutional, Full or part-time Employment: ClinPharmaResearch; Financial Interests, Personal and Institutional, Ownership Interest: ClinPharmaResearch. F. Ghiringhelli: Financial Interests, Institutional, Funding: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Honoraria, Travel, Accommodation, Expenses: Roche/Genentech; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Amgen. All other authors have declared no conflicts of interest.