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

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

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

Targeted probiotic therapy in irritable bowel syndrome: a clinical evaluation on Clostridium butyricum CBM588 and Bifidobacterium longum W11. (PubMed, Front Med (Lausanne)) - "Their strain-specific benefits highlight the potential of targeted probiotic strategies in IBS management. Future studies with larger sample sizes and longer follow-up periods are recommended to confirm and expand these findings."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

The Protective Effects of Lactobacillus reuteri Combined With Clostridium butyricum Miyairi 588 on Intestinal Barrier Function, Water Transport, and Oxidative Stress in a Rat Model of 5FU-Induced Diarrhea. (PubMed, Food Sci Nutr) - "5-Fluorouracil (5FU) is a commonly employed and highly effective chemotherapeutic agent in clinical oncology. LCs also notably diminished the mRNA expression levels of AQP7, VIP, and PKA. This study demonstrates that LCs have therapeutic effects on colitis, primarily through their antioxidant properties, anti-apoptotic effects, mucosal barrier integrity maintenance, neutrophil infiltration reduction, and inflammatory cytokines and aquaporin expression modulation."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • AKT1 • CASP3 • IFNG • IL1B • NFKB1 • OCLN • TNFA • VCAM1

Irritable Bowel Syndrome with Diarrhea (IBS-D): Effects of Clostridium butyricum CBM588 Probiotic on Gastrointestinal Symptoms, Quality of Life, and Gut Microbiota in a Prospective Real-Life Interventional Study. (PubMed, Microorganisms) - "These findings support the C. butyricum CBM588 probiotic strain as a safe, well-tolerated, and microbiota-targeted intervention for IBS-D. Randomized controlled trials are warranted to confirm efficacy."

HEOR • Journal • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Pain

CBM588 in Improving Clinical Outcomes in Patients Who Have Undergone Donor Hematopoietic Stem Cell Transplant (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Apr 2025 ➔ Mar 2026 | Trial primary completion date: Apr 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation

THE CLINICAL APPLICATION OF CLOSTRIDIUM BUTYRICUM MIYAIRI 588 FOR PATIENTS WITH COLORECTAL ADENOMATOUS POLYPS (DDW 2025) - "Its efficacy in modulating gut microbiota and enhancing intestinal barrier function highlights its clinical relevance. Future research should focus on larger, long-term studies to validate these findings and optimize its role in preventive oncology."

Clinical • Colonic Polyps • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Association between circulating B cell subtypes and treatment response in patients with metastatic renal cell carcinoma (mRCC) (AACR 2025) - "This study investigates the prognostic significance of circulating CD5+ B cells in mRCC patients (pts) treated with cabozantinib/nivolumab with or without CBM588, a live bacterial product. This open-label, randomized trial enrolled pts aged ≥18 years with histologically verified advanced or mRCC who had not received prior systemic therapy for metastatic disease... High baseline levels of CD5+ B cells are associated with inferior outcomes in patients with mRCC treated with cabozantinib and nivolumab. These findings suggest that CD5+ B cells may serve as a prognostic biomarker and a potential target to improve ICB outcomes in mRCC."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD5 • IL6

A novel combined immunotherapy of gut microbial metabolite butyrate and oncolytic adenovirus in colorectal cancer (AACR 2025) - "The combination therapy of CBM588 and OBP-702 demonstrated similar synergistic antitumor effects in mouse subcutaneous and rectal tumor models. In conclusion, the combination of OBP-702 and butyrate shows promise as a synergistic antitumor strategy and may represent a novel therapeutic approach for colorectal cancer."

IO biomarker • Oncolytic virus • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • TP53

Prognostic impact of Clostridium butyricum MIYAIRI (CBM588) in combination with pembrolizumab for advanced urothelial carcinoma (AUA 2025) - "All patients had recurrence or progression of UC after receiving cisplatin or carboplatin-based chemotherapy as first treatment. These findings might suggest that the arrangement treatment of gut microbiome using CBM588 has a prognostic impact for advanced UC patients undergoing pembrolizumab."

Combination therapy • Metastases • Gastric Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Hepatocellular Cancer • Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

CBM588 With Cabozantinib/Nivolumab Shows Promise in Metastatic RCC (Targeted Oncology) - P1 | N=31 | NCT05122546 | "...data from the phase 1 indicate that the addition of CBM588 to cabozantinib and nivolumab significantly improved progression-free survival (PFS) and objective response rate (ORR) in patients with mRCC. However, the study did not demonstrate a significant increase in Bifidobacterium spp., the primary end point, challenging initial hypotheses regarding the mechanism of action."

P1 data • Renal Cell Carcinoma

PROREDI: Study to Evaluate the Treatment Benefits of Probiotic Clostridium Butyricum CBM588® for IBS-D (clinicaltrials.gov) - P=N/A | N=400 | Completed | Sponsor: Liaquat University of Medical & Health Sciences | Trial completion date: Sep 2024 ➔ Mar 2025 | Initiation date: Sep 2023 ➔ Nov 2024 | Trial primary completion date: Mar 2024 ➔ Feb 2025

HEOR • Trial completion date • Trial initiation date • Trial primary completion date • Gastrointestinal Disorder

PROREDI: Study to Evaluate the Treatment Benefits of Probiotic Clostridium Butyricum CBM588® for IBS-D (clinicaltrials.gov) - P=N/A | N=400 | Completed | Sponsor: Liaquat University of Medical & Health Sciences | N=200 ➔ 400

Enrollment change • HEOR • Gastrointestinal Disorder

CBM588 Reduces Colorectal Polyp Recurrence (clinicaltrials.gov) - P=N/A | N=500 | Enrolling by invitation | Sponsor: Kaohsiung Medical University

New trial • Colonic Polyps • Colorectal Cancer

Clostridium Butyricum CBM588® vs. Rifaximin for Symptomatic Uncomplicated Diverticular Disease (SUDD) (clinicaltrials.gov) - P=N/A | N=70 | Completed | Sponsor: Dr. Amjad Khan

New trial • Gastroenterology • Gastrointestinal Disorder

CBM588 in Improving Clinical Outcomes in Patients Who Have Undergone Donor Hematopoietic Stem Cell Transplant (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation • TGFB1 • TNFA • TNFRSF1A

Dose finding study of CBM588 in combination with nivolumab and ipilimumab in patients with metastatic renal cell carcinoma: A phase I study. (ASCO-GU 2025) - P1 | "Dose level one has been completed without dose-limiting toxicities. Enrollment at dose level two began in October 2024."

Clinical • Combination therapy • Metastases • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • 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

Boosting survival in advanced urothelial carcinoma: The power of CBM588 probiotic and pembrolizumab combination. (ASCO-GU 2025) - "The combination of CBM588 with pembrolizumab may prolong progression in UC. Although the sample size and follow-up period are limited, the positive outcomes observed emphasize the necessity for further studies to confirm these findings and investigate the underlying causes. Multivariate analysis of PFS and OS.*p<0.05; **p<0.008."

Metastases • Genito-urinary Cancer • Kidney Cancer • Oncology • Solid Tumor • Urothelial Cancer

CBM588 Plus Cabozantinib/Nivolumab Shows Early Activity in Metastatic Renal Cell Carcinoma (OncLive) - P1 | N=31 | NCT05122546 | "CBM588 plus cabozantinib (Cabometyx) and nivolumab (Opdivo) improved progression-free survival (PFS) and objective response rate (ORR) but did not lead to a significant increase in Bifidobacterium spp. in patients with metastatic renal cell carcinoma (mRCC), according to updated data from a phase 1 study (NCT05122546) shared during the 2025 Genitourinary Cancers Symposium....The addition of CBM588 to cabozantinib and nivolumab (n = 20) led to a median PFS of 19.7 months vs 13.4 months with cabozantinib plus nivolumab (n = 10; HR, 0.74; 95% CI, 0.25-2.23; P = .59). With CBM588 plus cabozantinib and nivolumab, the partial response (PR) rate was 84%; the stable disease (SD) rate was 5% and the progressive disease (PD) rate was 11%. With cabozantinib plus nivolumab, the PR rate was 20%; SD and PD rates were 50% and 30%, respectively."

P1 data • Renal Cell Carcinoma

Enhancing the Immunogenicity of Nivolumab plus Ipilimumab with Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma. (PubMed, Eur Urol Focus) - "Dysbiosis may hinder effective tumor immunity and reduce the efficacy of therapies such as immune checkpoint blockade (ICB) in renal cell carcinoma (RCC). CBM588, a product containing live Clostridium butyricum, has shown promise in enhancing ICB effectiveness in metastatic RCC in terms of response rates and progression-free survival. Further research to confirm these findings should take factors such as diet and microbiome composition into account and include predictive biomarkers for patient selection."

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