Abstract CT242: Phase 2b study of alloHSCT patients receiving RGI-2001, an NKT cell activator, demonstrates safety and protection from acute GVHD, correlating with increased NKT cell number in patient blood

Abstract Background: Allogeneic hematopoietic stem cell transplant (alloHSCT) has potentially curative outcomes for patients with certain hematologic malignancies but also has toxicity due to graft-versus-host-disease (GVHD), where donor-derived T cells attack the immune suppressed recipient, leading to significant mortality and morbidity. Natural killer T (NKT) and T-regulatory (Treg) cell levels in the donor product or in the recipient associate with protection from acute GVHD (aGVHD) and thus may represent therapeutic targets. RGI-2001 is a liposomal formulation of an NKT cell agonist, expanding both NKT and Tregs in animal models, resulting in prevention of aGVHD without compromising general immune function. Phase 1/2a studies of RGI-2001 demonstrated safety and potential efficacy in reducing aGVHD in alloHSCT using single doses. In this Phase 2b study, RGI-2001 was given weekly x 6 doses (100 ug/kg) in combination with standard GVHD prophylaxis. Results: RGI-2001 was given to 48 subjects undergoing matched (8/8) alloHSCT. Control data from the CIBMTR (n=207) was obtained and used as comparison. Patients receiving RGI-2001 did not have any serious infusion reactions, related serious adverse events, cases of cytomegalovirus disease, post-transplant lymphoproliferative disease, or graft failure. Compared to the CIBMTR group, the RGI-2001 group demonstrated lower grade II-IV aGVHD (day 180) and higher aGHVD-free survival (GFS) and overall survival. Relapse and cGVHD rates were similar between the groups. In addition, the number of NKT cells in the blood of the RGI-2001 group correlated with specific outcomes within this group. Grade II-IV at day 100 or d180 or GFS d180 occurred in 8 patients, and the mean NKT numbers at day 28 for these patients is lower than patients without occurrence. The number and percentages of Tregs, CD4+ T cells, CD8+ T cells, and NK cells did not correlate with any clinical endpoints. Conclusions: RGI-2001 given weekly x 6 doses is safe and well tolerated. Compared to matched cohort, the RGI-2001 cohort had decreased aGVHD and increased overall survival, suggesting that RGI-2001 could be added to alloHSCT regimens to reduce aGVHD while not affecting overall immune responses against infection and tumor relapse. Future studies will focus on optimizing dosage based on blood levels of NKT cells, elucidating the mechanisms of actions of RGI-2001, and identifying potential biomarkers of response. Citation Format: Jack D. Bui, Calvin Lee, Christine Caron, Dana Lee, Zachariah DeFilipp, Yi-Bin Chen. Phase 2b study of alloHSCT patients receiving RGI-2001, an NKT cell activator, demonstrates safety and protection from acute GVHD, correlating with increased NKT cell number in patient blood abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT242.