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774 RGI-2001 Infusion for Prevention of Acute Gvhd after Allogeneic Hematopoietic Cell Transplantation

Program: Oral and Poster Abstracts
Type: Oral
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Novel Therapies for Graft-versus-Host Disease
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Monday, December 12, 2022: 11:45 AM

Yi-Bin Chen, MD, MS1, Ayman Saad, MD, MSc2*, Shatha Y. Farhan, MD3, Lazaros J. Lekakis, MD4*, Gary J. Schiller, MD5, Jean A. Yared, MD6, Amer Assal, MD7, Dana D Lee, PharmD8*, Hayley Lane9*, Ted A. Gooley, Ph.D.10* and Zachariah Defilipp, MD1

1Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA
2James Cancer Center, Ohio State Medical Center, Columbus, OH
3Henry Ford Hospital, Detroit, MI
4Sylvester Comprehensive Care Center, Division of Transplantation and Cell Therapy, University of Miami Health System, Miami, FL
5David Geffen School of Medicine at UCLA, Los Angeles, CA
6Transplantation & Cellular Therapy Program, Division of Hematology/Oncology, Department of Internal Medicine, University of Maryland Greenebaum Cancer Center, Baltimore, MD
7Blood and Marrow Transplantation Program, Columbia University Medical Center, New York, NY
8Regimmune Corporation, Marina Del Rey
9Regimmune Corporation, Marina Del Rey, CA
10Fred Hutchinson Cancer Center, Seattle, WA


Acute graft-versus-host disease (aGvHD) is a major cause of early morbidity after allogeneic hematopoietic cell transplantation (alloHCT). Despite the use of prophylactic immunosuppressive therapy, aGvHD occurs in 40% -60% of matched related and unrelated alloHCT and severe cases contribute to non-relapse mortality.

RGI-2001 is a liposomal glycolipid that binds CD1d receptor of antigen-presenting cells (APC) resulting in activation of invariant natural killer (iNKT) cells. This interaction results in a cytokine-dependent Treg proliferation with subsequent modulation of the GvHD pathogenic cascade. RGI-2001 is being evaluated for the potential to reduce or prevent aGvHD after alloHCT. Earlier studies had shown that a single dose of RGI-2001 given on the day of hematopoietic cell transplantation was safe and potentially contributed to aGvHD prevention.

Methods: RGI-2001-003 (NCT04014790) is an open-label, multi-center phase 2b study to evaluate the potential efficacy and safety of RGI-2001 when added to calcineurin inhibitor with methotrexate or mycophenolate mofetil (without T-cell depletion) for the prevention of aGvHD in subjects following myeloablative alloHCT. RGI-2001 was administered in a 30-minute infusion at a dose of 100 ug/kg IV infusion weekly x 6 doses, starting on the day of transplant (Days 0, 7, 14, 21, 28, 35). The primary endpoint of the phase 2b study was grade II-IV acute GVHD by Day 100.

Results: A total of 53 subjects were screened and 49 treated at 7 U.S. transplant centers. Median age was 52 (range 21-65). The most common underlying indications for alloHCT were AML(n=27, 55%), ALL (n=11, 22%), and MDS (n=7, 14%). Donors were HLA-matched related (n=15), match unrelated (n=28) or mismatched unrelated (n=6, 5 HLA DQ and 1 HLA-A). Graft source was peripheral blood progenitor cells (n=40) or bone marrow (n=9). Common myeloablative conditioning regimens included Fludarabine/ Busulfan (81.6%), Cyclophosphamide/TBI (12.2%), and Cytarabine/Cyclophosphamide/TBI (4%). All subjects received tacrolimus/methotrexate for GvHD prophylaxis.

Preliminary results are reported herein with all 49 subjects having completed study day 100. There were no reported serious infusion reactions and one subject received 5 of 6 doses due to a treatment related AE (increased ALT, grade 3). Treatment-emergent AE (TEAE) related to RGI-2001 (> 5%) were diarrhea (12%), nausea (12%), abdominal pain (8%), increased ALT (6%), increased alkaline phosphatase (6%), and rash (6%). Grade 3/4 related TEAE (>1 subject) were decreased neutrophil count (6%), decreased platelet count (4%), anemia (4%), stomatitis (4%) and decreased appetite (4%). Serious adverse events reported were sepsis, upper respiratory tract infection, diarrhea, headache, VOD, pelvic pain and DVT; none were deemed related to RGI-2001. There were no cases of engraftment failure.

All 49 patients had at least 100 days of follow-up (FU), and 39 of 49 had complete FU to day 180. The median FU of survivors was 310 days (range, 111-365). Through day 100, there were 10 cases of grades II-IV aGvHD [20.4% (95% confidence interval 10.2-34.3%)], two of which were grades III-IV aGvHD [(4.1% (0.5-14.0%)]. One subject died from aGvHD due to GI bleed. There have been 3 relapses, 3 deaths, and 7 cases of moderate (0 severe cases) chronic GVHD (cGVHD) by last contact. Day-180 estimates of overall survival (OS), grades II-IV aGvHD-free survival (GFS), and relapse were 93.6% (81.6-97.9%), 75.2% (60.5-85.1%), and 4.1% (0.7-12.6%), respectively. Figure 1 summarizes the probability of OS and GFS as a function of time.

Conclusions: Intravenous administration of RGI-2001 added to standard-of-care tacrolimus / methotrexate showed promising efficacy in the prevention of clinically significant aGVHD with a favorable safety profile. A phase 3 study is planned.

Disclosures: Chen: Novartis: Consultancy; Incyte: Consultancy; Daiichi: Consultancy; Equillium: Consultancy; Celularity: Consultancy; Magenta: Consultancy. Saad: Kite/Gilead: Consultancy; Magenta Therapeutics: Consultancy; Incyte: Consultancy; CareDx: Consultancy; In8Bio Inc: Patents & Royalties. Schiller: Samus: Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Takeda: Research Funding; AstraZeneca: Honoraria; Stemline: Research Funding; Millennium: Research Funding; Cellectis: Research Funding; Amgen: Current equity holder in publicly-traded company, Honoraria; Janssen: Research Funding; Deltafly: Research Funding; Bristol Myers Squibb: Current equity holder in publicly-traded company, Speakers Bureau; Geron: Research Funding; PreCOG LLC: Research Funding; Forma: Research Funding; Sellas: Research Funding; Novartis: Honoraria, Other: Speaker fees, Research Funding; Onconova: Research Funding; Ono Pharma: Honoraria; Genentech-Roche: Research Funding; Actuate: Research Funding; Cyclacel: Research Funding; Jazz: Consultancy; AVM Biopharma: Research Funding; Arog: Research Funding; Constellation: Research Funding; Daiichi-Sankyo: Research Funding; Kite, a Gilead Company: Research Funding, Speakers Bureau; Medimmune: Research Funding; CTI: Research Funding; Stemline: Speakers Bureau; Deciphera: Research Funding; Tolero: Research Funding; Sangamo: Research Funding; Regimmune: Research Funding; Mateon: Research Funding; Cellerant: Research Funding; AltruBio: Research Funding; Karyopharm: Research Funding, Speakers Bureau; Trovagen: Research Funding; Gamida: Research Funding; Glycomimetics: Research Funding; Incyte: Other: speaker fees, Research Funding, Speakers Bureau; FujiFilm: Research Funding; Gilead: Research Funding; Pfizer: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; Astellas: Research Funding, Speakers Bureau; Agios: Consultancy, Honoraria; Actinium: Research Funding; AbbVie: Research Funding, Speakers Bureau. Yared: Kite: Honoraria. Assal: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Guidepoint Inc: Consultancy; Alphasights: Consultancy; Curio Science: Consultancy. Lane: Regimmune Corporation: Consultancy. Defilipp: Taiho Oncology: Research Funding; Syndax Pharmaceuticals: Consultancy; Kadmon: Consultancy; Omeros: Consultancy; Regimmune: Research Funding; Incyte: Consultancy, Research Funding.

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