A live biotherapeutic product for adult allogeneic hematopoietic cell transplantation recipients: a partially randomized, placebo-controlled phase 1b trial
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Gastrointestinal (GI) microbiome disruption and impaired GI barrier integrity increase the risk of bloodstream infection (BSI) following allogeneic hematopoietic cell transplant. Here we report results from a two-cohort (open-label, n = 15; randomized, placebo-controlled, n = 45) phase 1b study of SER-155, an investigational, cultivated, multi-strain, oral live biotherapeutic designed to address GI microbiome disruption GI epithelial barrier integrity in allogeneic hematopoietic cell transplant recipients. In cohort 2, 34 of 45 participants received either SER-155 treatment (n = 20, SER-155 following microbiome conditioning with oral vancomycin), or placebo (n = 14), and subsequently received transplant. For the primary safety endpoint, SER-155 was well tolerated, with a safety profile comparable to placebo, no treatment-related serious adverse events and no infections with SER-155 species; the most common adverse events were diarrhea and nausea. Four participants in cohort 1 and four participants in cohort 2 (two participants in the SER-155 arm and two in the placebo arm) died during the study; none was attributable to SER-155. For the primary pharmacokinetic endpoint, engraftment was detected for 16 of 16 SER-155 strains, with a median of 11.5 strains detected after the first treatment course. The key secondary efficacy endpoint revealed a significantly lower incidence of BSI with SER-155 versus placebo (10.0% versus 43%; OR 0.15; 95% CI 0.01–1.13; P = 0.0423; 77% relative risk reduction). Other secondary efficacy endpoints (GI infection, acute graft-versus-host disease ≥grade 2, febrile neutropenia and a composite endpoint of BSI, GI infection or acute graft-versus-host disease) were not statistically significant. The secondary pharmacodynamic endpoint of GI domination by Enterococcus and Enterobacteriaceae spp. was not achieved. ClinicalTrials.gov identifier: NCT04995653 . In a phase 1b study that included an open-label and randomized-controlled cohorts of allogeneic hematopoietic cell transplantation recipients, treatment with the investigational, cultivated, multi-strain bacterial oral live biotherapeutic product, SER-155, was found to have a similar safety profile to placebo and resulted in fewer bloodstream infections, indicating further clinical investigation of this therapeutic is warranted.
Source: Nature Medicine
Authors: Doris M. Ponce, Zachariah DeFilipp, Christopher B. Ford, Bina Tejura, Mary-Jane Lombardo, David I. Lichter, Meghan Chafee, Satyajit Kosuri, Nandita Khera, Hemant S. Murthy, Karamjeet S. Sandhu, David N. Fredricks, Tessa Andermann, Rajneesh Nath, Kelly Brady, Brooke R. Hasson, Emily Walsh, Nathan Hicks, Jonathan U. Peled, Lisa von Moltke, Matthew R. Henn, Marcel R. M. van den Brink, Dennis M. Walling, the SER-155-001 Study Team, William J. Hogan, Nosha Farhadfar, Steven Tsai, Zeina Al-Mansour, Chirag Patel, Swarna Pandian, Kankana Bardhan, Sean Sykes
Institutions: Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Massachusetts General Hospital, Seres Therapeutics (United States), University of Chicago, Mayo Clinic Hospital, Mayo Clinic in Florida, Mayo Clinic Comprehensive Cancer Center (Florida), City Of Hope National Medical Center, Fred Hutch Cancer Center, University of North Carolina at Chapel Hill, Banner Health, Rutgers Cancer Institute, Mayo Clinic, UF Health Shands Hospital, University of Florida, University of California, Los Angeles
Language: English
Subfield: Food Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7225149724