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

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

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

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

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 | "Clinical Trial Registry Number: NCT06399419. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

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

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 | "Clinical Trial Registry Number: NCT05122546 & NCT03829111. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

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

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

Prognostic Impact of Clostridium butyricum MIYAIRI (CBM588) in Combination With Pembrolizumab for Advanced Urothelial Carcinoma: A Retrospective Cohort Study. (PubMed, Cancer Rep (Hoboken)) - "These results suggest the effectiveness of the CBM588 combination with ICI treatment in UC."

Journal • Retrospective data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Perioperative administration of CBM588 in colorectal cancer radical surgery: A single-center, randomized controlled trial. (PubMed, Cell Rep Med) - P4 | "We find that perioperative administration of CBM588 significantly benefits recovery of intestinal function, lowers risk of infectious complications, and enhances systemic immunity by increasing circulating T cells. CBM588 serves as a promising probiotic with favorable tolerability in CRC patients undergoing radical surgery."

Journal • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Oncology • Solid Tumor

Clostridium butyricum enhances cognitive function in APP/PS1 mice by modulating neuropathology and regulating acetic acid levels in the gut microbiota. (PubMed, Microbiol Spectr) - "Our comprehensive evaluation of CBM588 demonstrates its remarkable potential to ameliorate cognitive impairment in APP/PS1 mice by modulating gut microbiota composition, upregulating short-chain fatty acids, particularly acetate, and mitigating neuroinflammation. These findings not only provide novel insights into the gut-brain axis in AD but also offer a promising therapeutic strategy, highlighting the importance of targeting gut microbiota in future AD research and interventions."

IO biomarker • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • BAX • BCL2 • CLDN1 • IL1B • IL6 • OCLN • TJP1 • TNFA

Adding a Probiotic (CBM588) to Pembrolizumab for the Treatment of Renal Cell Cancer After Surgery (clinicaltrials.gov) - P2 | N=62 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CXCL8

Effect of Clostridium butyricum and antibiotics using simultaneous simple suspension in mice with Clostridioides difficile infection. (PubMed, Exp Mol Pathol) - "This study using mice demonstrates the effectiveness of simultaneous simple suspensions of CBM and antibiotics in treating CDI. This approach significantly reduces C. difficile counts, modulates cytokine levels, and maintains probiotic viability, potentially making it a viable option for administration via gastric tubes in clinical settings."

Journal • Preclinical • Infectious Disease • Oncology • IFNG • IL10 • IL6 • TNFA

Combination therapy with levofloxacin and the probiotic Clostridium butyricum MIYAIRI 588 enhances immune checkpoint inhibitor efficacy. (PubMed, Int J Cancer) - "A broad-spectrum antibiotic cocktail (ampicillin, neomycin, vancomycin, and metronidazole) with CBM588 diminished antitumor effects and reduced survival in mice when compared with the control, demonstrating the importance of microbiota-targeted therapeutic combinations. However, while LVFX+CBM588 improved ICI efficacy, it worsened dextran sulfate sodium (DSS)-induced colitis, suggesting immune activation contributes to inflammation. These findings emphasize the potential of customized antibiotic-probiotic combinations in cancer immunotherapy, while also stressing the necessity to manage immune-related adverse effects."

Checkpoint inhibition • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology