NCT04944888

GSL Synthetase Inhibitor in Combination With Immune Checkpoint Inhibitor in Previously Treated Blood and Solid Tumor

Phase ⅠStudy of GSL Synthetase Inhibitor in Combination With Immune Checkpoint Inhibitor in Treating Patients With Advanced Relapsed or Refractory Hematological Malignancies and Previously Treated Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 16 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Immune checkpoint blockade has made great but unsatisfied success in treating cancers. One important reason is the hijacked HLA (Human Leukocyte Antigen) antigen presentation. Eliglustat could inhibit glycosphingolipids synthesis and restore HLA-I antigen presentation and transform the immunogenicity of tumor cells. Therefore,GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor may explore a new avenue for therapeutic intervention in cancer.

Detailed description

Immune checkpoint blockade has led to great strides in the management of various cancers, however, durable response could be seen in approximately 20% of treated patients with most solid tumors and hematological malignancies. One important reason is that tumor cells often escape from immune surveillance by downregulating one or multiple molecules critical in HLA antigen presentation. As a consequence, options that could restore HLA antigen presentation may augment immune checkpoint inhibitor-mediated immune responses. Abnormal expression of glycosphingolipid (GSL) synthetase is a basic and specific characteristic of most tumors and tumor microenvironment, such as Globo H Ceramide, which is overexpressed in multiple epithelial-derived tumors. Several studies also reported that GSL synthetase was overexpressed in chemotherapy-resistant tumors. Eliglustat is an orally GlcCer synthase inhibitor, which is approved for treating Type-1 Gaucher disease. However, one most recent study reveals that it could inhibit glycosphingolipids synthesis and restore HLA antigen presentation, and transforming the immunogenicity of tumor cells. Therefore, GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor may explore a new avenue for therapeutic intervention in cancer. The primary objective of this study is to assess the safety and feasibility of GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor in patients with relapsed or refractory hematological malignancies and solid tumors. The secondary objectives include assessing antitumor activity, pharmacokinetics and pharmacodynamics. The exploratory objectives are to evaluate the pathological, immunological or clinical predictive biomarkers for efficacy and toxicity, transformation of tumor microenvironment and dynamic changes of immune cells in peripheral blood.

Conditions

• Solid Tumor
• Hematologic Malignancy

Interventions

Type	Name	Description
DRUG	Eliglustat	Eliglustat will be given to enrolled patients at dose of 84mg daily (dose 1) , and then at dose of 84mg twice daily (dose 2).
DRUG	Immune checkpoint inhibitor	immune checkpoint inhibitor (physician decided).

Timeline

• Start date: 2021-07-01
• Primary completion: 2023-11-30
• Completion: 2023-11-30
• First posted: 2021-06-30
• Last updated: 2023-12-19

Locations

1 site across 1 country: China