A phase 1b study to evaluate the efficacy, safety, and pharmacokinetics of an investigational microbiome therapeutic, SER-155, in adults undergoing hematopoietic stem cell transplantation.

Abstract

TPS7080 Background: In patients undergoing allogeneic hematopoietic cell transplantation (HCT), loss of gastrointestinal microbial diversity is associated with risk of bloodstream infections (BSI), acute graft-versus-host disease (aGvHD), and death. SER-155 is a rationally designed investigational cultivated microbiome therapeutic, hypothesized to improve clinical outcomes in HCT by restoring colonization resistance to potential pathogens, promoting epithelial barrier integrity, and reducing colonic inflammation. SER-155-001 is a Phase 1b study evaluating the efficacy, safety, and pharmacokinetics (PK) of SER-155 in adults undergoing HCT. Methods: This study will enroll approximately 70 subjects ≥18 years in an open-label Cohort 1 (n = 10) followed by a double-blind, placebo-controlled Cohort 2 (n = 60) randomized 1:1 to SER-155 or placebo. A variety of conditioning regimens, donor types, and GVHD-prophylaxis regimens are included. Exclusion criteria include history of severe colitis or active inflammatory bowel disease or total colectomy, umbilical cord blood or ex vivo T-cell depletion, exposure to fecal microbiota transplant or any live microbial therapeutic within 3 months prior to screening, and evidence of relapse or progression of hematologic malignancy (minimal residual disease is allowed). Following screening, participants in both cohorts receive 2 treatment courses (one before and one after HCT), each comprised of microbiome conditioning with oral vancomycin or placebo followed by SER-155 or placebo, plus a conditional 3rd treatment course if the subject receives antibiotics. Safety outcomes are followed through 52 weeks post HCT. The primary endpoint is the incidence and severity of adverse events, serious adverse events, and adverse events of special interest. Secondary endpoints include rates of BSI, gastrointestinal infections, aGvHD, febrile neutropenia and overall survival. Microbiome related endpoints include engraftment of SER-155 bacterial strains in the gastrointestinal tract (PK endpoint) and fecal microbiome diversity, composition and metabolites. Results: Cohort 1 enrollment is complete, with 13 participants receiving SER-155. In December 2022, the Data and Safety Monitoring Committee supported continuation to Cohort 2 enrollment following review of safety data from Cohort 1. Enrollment in Cohort 2 is underway. Conclusions: This Phase 1b study is designed to assess the safety, and clinical efficacy of SER-155 in allogeneic HCT, expanding the clinical experience of microbiome- directed interventions in allogeneic HCT recipients. Clinical trial information: NCT04995653 .