Galecto Begins Dosing in Phase 2 Trial of GB1211 with Pembrolizumab

Galecto, Inc., a clinical-stage biotechnology company listed on NASDAQ under the ticker GLTO, has initiated an investigator-led Phase 2 trial to evaluate their novel candidate, GB1211. GB1211, an oral small molecule galectin-3 inhibitor, is being tested in combination with pembrolizumab at the Earle A. Chiles Research Institute (EACRI), part of Providence Cancer Institute in Portland, Oregon. The trial, spearheaded by Dr. Brendan Curti and Dr. William Redmond, aims to assess the safety and efficacy of GB1211 for treating metastatic malignant melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). Recognized with an R01 Research Project Grant from the National Cancer Institute, the study will use a 100mg dose of GB1211 administered twice daily along with pembrolizumab.

Galectin-3 is known to be overexpressed in several cancers, including melanoma and HNSCC, where it is associated with tumor growth, invasiveness, and metastasis. High levels of galectin-3 in the tumor microenvironment can impede the effectiveness of checkpoint inhibitors like pembrolizumab by blocking their binding to targeted cells. Preclinical data indicates that GB1211 can mitigate this interference, thereby potentially overcoming resistance to immune checkpoint inhibitors (ICIs) caused by galectin-3.

In the latter part of 2023, Galecto shared promising results from its Phase 1b/2a GALLANT-1 trial which evaluated GB1211 in combination with atezolizumab for treating non-small cell lung cancer (NSCLC). The results showed a 60% objective tumor response rate among patients who received the recommended Phase 2 dose of GB1211, a notable improvement compared to the 22-38% response rate typically seen with atezolizumab monotherapy. These findings suggest a possible advantage of combining GB1211 with ICIs.

Dr. Curti, Medical Director of the Providence Melanoma Program and a member of EACRI, emphasized the importance of the bench-to-bedside research capabilities at the Providence Cancer Institute. He highlighted the insights from Dr. Redmond's lab on using galectin inhibitors to modify the tumor environment and enhance anti-tumor activity. Dr. Redmond, who leads the EACRI Immune Monitoring Lab and is a co-principal investigator for the trial, expressed enthusiasm about the potential to counteract ICI resistance in melanoma and HNSCC patients through this study.

Galecto’s CEO, Dr. Hans Schambye, shared his excitement about the initiation of this trial by Drs. Redmond and Curti, praising Dr. Redmond as a leading authority on galectin-3 in cancer and ICI resistance. Dr. Schambye noted that the encouraging results from the GALLANT-1 trial provide a strong foundation for exploring potential synergies with pembrolizumab in the new trial. He expressed optimism about GB1211’s ability to enhance the efficacy of ICIs in various cancer types.

The Phase 2 trial is randomized, double-blind, and placebo-controlled. It will assess whether adding GB1211 can increase the response rate of pembrolizumab in patients with metastatic melanoma and HNSCC. Patients with unresectable or metastatic MM or recurrent/metastatic HNSCC who have progressed during or after platinum-based chemotherapy will receive a fixed dose of GB1211 along with pembrolizumab. The study will monitor for toxicity and clinical response, and biospecimens will be collected to evaluate immunologic markers relevant to galectin biology and T-cell checkpoint inhibition. Tumor volume assessment will follow the immune response RECIST criteria (iRECIST criteria 1.1), with preliminary data expected as early as 2025.

GB1211 has demonstrated anti-cancer and anti-fibrotic effects in multiple preclinical models and showed favorable results in a Phase 1 trial with healthy volunteers. Galecto, headquartered in the U.S., focuses on small molecule inhibitors targeting galectin-3 and LOXL2, with multiple Phase 2 clinical opportunities in cancer and fibrosis.