Cdactin-O (CBM588) / Osel, Miyarisan - LARVOL DELTA

Microbiome modulation via CBM588 dampens T cell exhaustion in patients with metastatic renal cell carcinoma on dual immune checkpoint blockade (AACR 2026) - P1 | "While the combination of nivolumab (nivo) and ipilimumab (ipi) is currently one of the standard-of-care treatments for patients with metastatic renal cell carcinoma (mRCC), the majority of patients still suffer disease progression. Our results suggest that CBM588 may improve patient responses to ICIs by restraining CD8+ T cell amplification and attenuating features of T cell exhaustion. The CBM588+nivo+ipi dose escalation study is still ongoing with further immune correlative analyses pending."

Checkpoint block • Checkpoint inhibition • Clinical • IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CD8 • CTLA4 • HAVCR2 • IL7R • KLRG1

A RANDOMIZED PILOT TRIAL OF CLOSTRIDIUM BUTYRICUM MIYARI 588 IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS (EBMT 2026) - P1 | "Fludarabine/melphalan conditioning and tacrolimus/sirolimus GVHD prophylaxis were used; grafts were from matched related (n=14) or unrelated donors (n=22). CBM588 administration is safe, feasible, and modulates gut microbiome composition and function in HCT recipients, improving microbial diversity and trending toward reduced lower GI GVHD. Nutritional status strongly impacts microbiome dynamics and GVHD risk. Our data strongly support further investigation of microbiome-targeted interventions to improve transplant outcomes."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation • CD69 • CD8 • IL2 • IL6 • REG3A • TNFRSF1A

A RANDOMIZED PILOT TRIAL OF CLOSTRIDIUM BUTYRICUM MIYARI 588 IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS (EBMT 2026) - P1 | "Fludarabine/melphalan conditioning and tacrolimus/sirolimus GVHD prophylaxis were used; grafts were from matched related (n=14) or unrelated donors (n=22). CBM588 administration is safe, feasible, and modulates gut microbiome composition and function in HCT recipients, improving microbial diversity and trending toward reduced lower GI GVHD. Nutritional status strongly impacts microbiome dynamics and GVHD risk. Our data strongly support further investigation of microbiome-targeted interventions to improve transplant outcomes."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation • CD69 • CD8 • IL2 • IL6 • REG3A • TNFRSF1A

Long-term clinical outcomes with Clostridium butyricum MIYAIRI 588 (CBM588) and TOPOSCORE assessment in patients receiving immune checkpoint inhibitor (ICI)-based combinations for metastatic renal cell carcinoma (mRCC). (ASCO-GU 2026) - P1 | "Participants were randomized to receive nivolumab/ipilimumab or nivolumab/cabozantinib alone (standard of care [SOC]) or with CBM588 (SOC + CBM588)... In this pooled analysis of two randomized phase I trials, the addition of CBM588 to frontline ICI-based therapy was associated with higher ORR and prolonged PFS compared with SOC alone, supporting the design of the upcoming phase III SWOG BIOFRONT study. We also identify baseline TOPOSCORE as a potential predictor of benefit with dual ICI regimens."

Checkpoint inhibition • Clinical • Clinical data • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

First results of a dose-escalation study evaluating Clostridium butyricum MIYAIRI 588 (CBM588) with nivolumab/ipilimumab (nivo/ipi) in metastatic renal cell carcinoma (mRCC). (ASCO-GU 2026) - P1 | "No DLTs were encountered with CBM588 capsules at the highest dose level (MO-03) in combination with nivo/ipi, supporting the dosing strategy in the upcoming phase III SWOG study S2419 (BioFront). Translational studies indicate a dose effect upon microbiome composition, and sMAdCAM-1 dynamics suggest a potential association with response."

IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Probiotics Combined With Targeted Therapy Plus Immunotherapy in Bladder-Preserving Setting for Patients With MIBC (clinicaltrials.gov) - P2 | N=146 | Not yet recruiting | Sponsor: chenxu

New P2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • HER-2

Periodontitis promotes intestinal inflammation through gut microbiota-mediated suppression of GPR109A. (PubMed, Front Cell Infect Microbiol) - "Further, the probiotic strain CBM588 was supplemented to two groups of mice (CP/LP group) to alleviate periodontitis-induced inflammation, and GPR109A expression was detected...Finally, GPR109A function was modulated by administration of GSK256073 and mepenzolate bromide in ligatured mice, and corresponding changes in tight junctional integrity as well as intestinal and systemic inflammation were evaluated...Periodontitis promotes colonic inflammation by gut microbiota-induced suppression of GPR109A receptor, leading to the destruction of the epithelial barrier. Activation of GPR109A restores barrier function and attenuates inflammation."

Journal • Dental Disorders • Inflammation • Inflammatory Bowel Disease • Periodontitis • Transplantation • OCLN • TJP1

CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CXCL8

Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer (clinicaltrials.gov) - P3 | N=718 | Not yet recruiting | Sponsor: SWOG Cancer Research Network

New P3 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

PAN-CLO-BU (PANcreas-CLOstridium-BUtyricum) (clinicaltrials.gov) - P=N/A | N=158 | Not yet recruiting | Sponsor: Casa di Cura Dott. Pederzoli

New trial • Gastrointestinal Disorder • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor

Clinical outcomes with nivolumab/ipilimumab (nivo/ipi) with or without CBM588 in metastatic renal cell carcinoma (mRCC): Long-term follow-up of a randomized phase Ib clinical trial (IKCS 2022) - "Although limited by sample size, nivo/ipi/CBM588 demonstrated superior clinical activity over nivo/ipi. PFS and ORR with nivo/ipi/cbm588 also exceeded those observed with nivo/ipi in historical datasets. Larger efforts investigating gut microbiome modulation via CBM588 are warranted."

Clinical • Clinical data • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Cabozantinib (cabo) and nivolumab (nivo) with or without CBM588 in patients with metastatic renal cell carcinoma: Updated clinical outcomes of a phase I study. (ASCO-GU 2025) - P1 | "The addition of CBM588 to cabo/nivo continues to show promising efficacy in mRCC, with an improved PFS and ORR. The safety profile remains consistent with previous findings, supporting further exploration in larger trials. Further translational efforts are underway to characterize the mechanism through which CBM588 augments clinical activity."

Clinical • Clinical data • Metastases • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Characterization of the microbial resistome in a prospective trial of CBM588 in metastatic renal cell carcinoma (mRCC) offers mechanism for interplay between antibiotic (abx) use and immune checkpoint inhibitor (ICI) activity. (ASCO 2022) - P1 | " Pts with newly diagnosed mRCC with clear cell and/or sarcomatoid histology and intermediate/high risk disease per IMDC criteria were randomized to nivolumab/ipilimumab (nivo/ipi) or nivo/ipi/CBM588 in a 1:2 ratio...More specifically, nivo/ipi/CBM588 treatment led to a significant reduction in fosfomycin RGs and nitroimidazole (e.g., metronidazole) RGs in both pts with R (p = 0.019 and 0.042, respectively) and NR (p = 0.031 and p = 0.031, respectively). A multitude of other clinically relevant abx RGs were downregulated in pts receiving CBM588, including those mediating resistance to glycopeptide (e.g., vancomycin) and lincosamide (e.g., clindamycin) abx... In the first interrogation of the resistome in mRCC, we demonstrate that CBM588 decreases abx RGs associated with multiple commonly used classes of abx. Abx clear commensals and increase pathogenic (abx resistant) bacteria in the gut. Based on our data, we formulate the hypothesis that combining abx with CBM588..."

Checkpoint inhibition • Clinical • Genito-urinary Cancer • Immune Modulation • Inflammation • Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial. (ASCO 2023) - P1 | "In the second prospective trial assessing the addition of CBM588 to ICI-based therapy in mRCC, a consistent result with improved PFS and RR was observed. Further translational efforts are underway to characterize the mechanism through which CBM588 augments clinical activity. Clinical trial information: NCT05122546."

Clinical • Combination therapy • Late-breaking abstract • Metastases • Genito-urinary Cancer • Immune Modulation • Immunology • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Combination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC). (ASCO-GU 2024) - P1 | "CheckMate214 demonstrated a survival advantage with ipi/nivo over sunitinib; unfortunately, 20% of cases developed primary progression to immunotherapy...Our group has previously proven that the addition of a live bacterial product (CBM588) enhances clinical responses in pts with mRCC treated with ICI, and the combination of ICI (Dizman et al., 2022) or with a tyrosine kinase inhibitor (Ebrahimi et al., 2023)...The study is currently open to enrollment. Clinical trial information: NCT06049576."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD4 • CD8

Long-term clinical outcomes with nivolumab/ipilimumab with or without Clostridium butyricum MIYAIRI588 in metastatic renal cell carcinoma (mRCC): A randomized phase Ib clinical trial. (ASCO 2025) - P1 | "Although limited by the sample size, the combination of nivolumab/ipilimumab with CBM588 demonstrated superior clinical activity over nivolumab/ipilimumab in our cohort. Additionally, ORR, PFS and OS with nivo/ipi/CBM588 exceeded those observed with nivolumab and ipilimumab in historical datasets (Motzer et al. NEJM)."

Clinical • Clinical data • Metastases • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Evolution of the functionality of microbial communities in patients with metastatic renal cell carcinoma (mRCC) receiving cabozantinib (cabo)/nivolumab (nivo) with or without CBM588: A randomized clinical trial. (ASCO-GU 2024) - P1 | "Our interrogation of metabolic dynamics and pathways in patients receiving CBM588 suggests key differences in biosynthesis pathways of menaquinone between control and experimental arms. Menaquinones (vitamin K2 derivatives) have been previously reported to induce apoptosis in many cancer cell types and also increase the objective response rate to sorafenib in patients with hepatocellular carcinoma. Our findings provide mechanistic evidence for the effect of the addition of CBM588 to cabo/nivo on gut microbiome function and the resultant improvement in clinical outcomes in mRCC, potentially through enhancing the enteric production of vitamin K2."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. (PubMed, Nat Med) - P1 | "The data suggest that CBM588 appears to enhance the clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab-ipilimumab. Larger studies are warranted to confirm this clinical observation and elucidate the mechanism of action and the effects on microbiome and immune compartments."

Journal • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. (PubMed, Nat Med) - P1 | "Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab...Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546."

Journal • Metastases • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • AXL

Clostridium butyricum MIYAIRI 588 Reduces Colorectal Adenomatous Polyp Recurrence: A Randomized Crossover Trial. (PubMed, Oncol Res) - "CBM588 was well tolerated, with no serious adverse events. CBM588 demonstrated potential to reduce colorectal adenoma recurrence in high-risk patients, supporting its role as a feasible, non-invasive preventive strategy."

Clinical • Journal • Colonic Polyps • Colorectal Cancer • Oncology • Solid Tumor

Microbiome and cytokine features are associated with graft-versus-host disease incidence in allogeneic hematopoietic cell transplantation patients (ASH 2025) - P1 | "Methods The cohort consisted of 30 patients; half received Clostridium butyricum MIYAIRI 588 (CBM588) and half received placebo treatment as part of a pilot clinical trial investigating the safety of CBM588 administration in transplant recipients undergoing reduced intensity conditioning regimen (NCT03922035)...Conclusion The link between intestinal microbiota and the incidence of aGVHD could be related with an increase in pro-inflammatory cytokines, such as IL-8 and IL-6, after allo-HCT. Understanding the molecular mechanisms that link specific taxonomic groups, such as Enterococcus and Phocaeicola species, with the triggering of cytokine release could help identify strategies to mitigate the incidence of aGVHD."

Clinical • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation • CXCL8 • IL10 • IL6 • TNFRSF1A

Poor nutritional intake prior to allogeneic hematopoietic cell transplantation is associated with higher incidence of lower-gastrointestinal graft-versus-host disease (ASH 2025) - P1 | "With acohort of patients from our Center, enrolled on a Clostridium butyricum MIYAIRI 588 (CBM588) pilot trial(NCT03922035), we explored how calorie and protein intake during allo-HCT correlate with microbiomecomposition /and incidence of lower gastrointestinal (GI) graft-versus-host disease (GVHD).Methods...These findings underscorethe need to investigate nutritional intake and clinical outcomes in larger cohorts. It highlights thepotential therapeutic opportunity of early nutritional intervention on microbiome and transplantoutcomes."

Graft versus Host Disease • Immunology • Transplantation

CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Oct 2025 ➔ Jan 2026 | Trial primary completion date: Oct 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CXCL8

Management of symptomatic uncomplicated diverticular disease (SUDD) of the colon with Clostridium butyricum CBM588 versus rifaximin: a retrospective cross-sectional study. (PubMed, Int J Colorectal Dis) - P=N/A | "In this retrospective comparison, Clostridium butyricum CBM588® demonstrated similar efficacy to rifaximin in preventing diverticulitis, with a potential advantage in subjective symptom improvement. These findings support further prospective studies to explore the role of CBM588® in SUDD management. Trial registration Clinicaltrial.gov reference: NCT06852274."

Clinical • Journal • Observational data • Retrospective data • Gastrointestinal Disorder • Pain

Probiotic Prophylaxis with Clostridium Butyricum for Postoperative Infections Following Lung Resection: A Propensity Score-Weighted Analysis. (PubMed, Ann Thorac Surg) - "Perioperative CBM588 may reduce OSS and all postoperative infections following thoracoscopic anatomical lung resection, suggesting a potential prophylactic benefit."

Journal • Infectious Disease • Lung Cancer • Oncology • Solid Tumor