Phase 1b: 16-strain oral consortium SER-155 linked to fewer bloodstream infections after transplant

Researchers from City of Hope, Memorial Sloan Kettering Cancer Center and Seres Therapeutics reported phase 1b results for SER-155, an investigational oral live biotherapeutic of 16 cultivated human-commensal bacterial strains. The study, published in Nature Medicine and available on nature.com, enrolled adults receiving allogeneic hematopoietic cell transplant (allo-HCT) in two cohorts: open-label (n = 15) and randomized, placebo-controlled (n = 45) nature.comnature.comnature.comOpen source ↗. In cohort 2, 34 participants received either SER-155 after microbiome conditioning with oral vancomycin (n = 20) or placebo (n = 14), and then underwent transplant nature.comnature.comnature.comOpen source ↗.

Gut microbiome and infection risk

Allo-HCT is performed about 40,000 times a year worldwide, mainly for hematological malignancies. Recipients are at increased risk of bloodstream infection (BSI) and graft-versus-host disease. BSI incidence reaches up to 45% within 30 days after transplant, and acute graft-versus-host disease occurs in 30–50% of patients nature.comnature.comnature.comOpen source ↗.

The authors note that the gastrointestinal tract is the main reservoir of bacteria that cause peri-transplant BSI. Conditioning regimens, post-transplant cyclophosphamide and antibiotics disrupt the microbiome and the gut barrier. According to the authors, no FDA-approved therapy currently addresses this disruption nature.comnature.comnature.comOpen source ↗.

SER-155 was designed to restore colonization resistance, improve mucosal barrier integrity and reduce local inflammation. Strains were selected from taxa that are depleted during the peri-transplant period nature.comnature.comnature.comOpen source ↗.

Trial results

For the primary safety endpoint, SER-155 was well tolerated, with a profile comparable to placebo. There were 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 in cohort 2 (two in each arm) died during the study; none of the deaths was attributed to SER-155 nature.comnature.comnature.comOpen source ↗.

For the primary pharmacokinetic endpoint, engraftment was detected for all 16 strains, with a median of 11.5 strains detected after the first treatment course nature.comnature.comnature.comOpen source ↗.

The key secondary endpoint showed lower BSI incidence with SER-155 than with placebo: 10.0% versus 43% (odds ratio 0.15; 95% CI 0.01–1.13; P = 0.0423; 77% relative risk reduction) nature.comnature.comnature.comOpen source ↗. Other secondary efficacy endpoints were not statistically significant: gastrointestinal infection, acute graft-versus-host disease of grade 2 or higher, febrile neutropenia, and a composite of BSI, gastrointestinal infection or acute graft-versus-host disease. The pharmacodynamic endpoint of gut domination by Enterococcus and Enterobacteriaceae was not achieved nature.comnature.comnature.comOpen source ↗.

The trial is registered as NCT04995653 and was sponsored by Seres Therapeutics.