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

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 | "Clinical Trial Registration Number: NCT03829111 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

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

A rapid genome-proteome approach to identify rate-limiting steps in the butyrate production pathway in probiotic Clostridium butyricum, CBM588. (PubMed, Anaerobe) - "Our findings pave the way for over-expressing these genes chromosomally to generate a recombinant probiotic with improved butyrate production and potentially enhanced gut health properties."

Journal

Preventive effect of Clostridium butyricum MIYAIRI against pouchitis in children with ulcerative colitis. (PubMed, Surg Today) - "Oral CBM administration after ileostomy closure may be effective in preventing postoperative pouchitis."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pediatrics • Ulcerative Colitis

Innovative strategies for the rapid restoration of intestinal function in patients undergoing abdominal surgery: use of probiotics. Pilot study of 15 patients. (PubMed, Minerva Gastroenterol (Torino)) - "This pilot randomized controlled trial aimed to assess the effects of perioperative and postoperative oral administration of two probiotics, Clostridium butyricum CBM588® and Bifidobacterium longum ES1, on immune function, systemic inflammatory response, postoperative infections, and recovery after colorectal surgery...Results showed the safety of probiotics, resistance to antibiotics and gastric acid, and potential benefits in reducing postoperative infections and intestinal inflammation. Future trials should provide more conclusive evidence on the efficacy and safety of perioperative probiotic administration in colorectal surgery, aiming for improved patient outcomes and reduced healthcare costs."

Journal • Surgery • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Systemic Inflammatory Response Syndrome

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 2024 ➔ Oct 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Combination therapy • Metastases • 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

Ulka Vaishampayan on Gut Microbiome Therapy in Kidney Cancer (MedPageToday) - "'Among genitourinary tumors, renal cell carcinoma (RCC) has been the area of most clinical trial research into the gut microbiome since immunotherapy is a mainstay of treatment in RCC,' said Ulka Vaishampayan, MBBS....Vaishampayan: CBM-588 has shown preliminary promise as per the clinical studies stated above. The next step in the development of microbiome therapy is to evaluate this in a phase III trial. Southwest Oncology group is developing a randomized clinical trial of combining frontline immune checkpoint-based therapy with CBM-588."

Media quote

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

HEOR • New trial • Gastrointestinal Disorder

Impact of Latino ethnicity on the gut microbiome and response to immune checkpoint inhibition (ICI) with CBM588 in patients (pts) with metastatic renal cell cancer (mRCC) (ESMO 2024) - "Herein we analyze the impact of CBM588 on the gut microbiome and clinical outcome between Latino and non-Latino pts with mRCC. We analyzed stool samples from two phase I trials that enrolled pts with mRCC treated with frontline nivolumab/ipilimumab or nivolumab/cabozantinib +/- CBM588... Latino pts who received ICI with CBM588 had a higher DCR as compared to non-Latino pts. Additionally, they exhibited increased bacterial spp linked to favorable outcomes with ICIs. Our findings suggest that trials aimed at modulating the microbiome could have unique value in minority populations."

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

Dr Dizman on the Impact of CBM588 on the Gut Microbiome in ICI-Treated Patients With RCC (OncLive) - "The pooled analysis focused on microbiome diversity, a common metric in microbiome research....However, findings presented at the 2024 Kidney Cancer Research Summit showed that the addition of CBM588 to checkpoint inhibitors did not result in an increase in diversity or improvement in the richness of the gut microbiome...Despite the lack of increased diversity, CBM588 showed notable effects on specific bacterial species associated with positive outcomes in patients receiving immune checkpoint blockade therapies...For instance, Eubacterium cerium, which typically declines in the standard of care arm, maintained stable abundance in the CBM588 arm."

Retrospective data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Potential role of gut microbiota in major depressive disorder: A review. (PubMed, Heliyon) - "Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Transplantation