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

Phase I dose-finding study evaluating Clostridium butyricum MIYAIRI 588 (CBM588) with nivolumab/ipilimumab (nivo/ipi) in metastatic renal cell carcinoma (mRCC) (ESMO 2026) - No abstract available

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

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

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

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

Assessment of short-chain fatty acid (SCFA) and circulating cytokine trends in a clinical trial of nivolumab/ipilimumab and CBM588 in metastatic renal cell carcinoma (mRCC). (ASCO 2023) - P1 | "A substantial increase in isobutyrate levels in CBM588 responders is indicative of altered amino acid metabolism (specifically, valine and leucine) by modified gut flora in these patients. These observations, combined with alterations in serum cytokines, provide biologic rationale for the clinical activity seen with CBM588 in combination with nivolumab/ipilimumab in this trial. Clinical trial information: NCT03829111."

Clinical • Metastases • Genito-urinary Cancer • Immune Modulation • Melanoma • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CCL2

Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC). (ASCO 2024) - " We analyzed stool samples from two phase I randomized clinical trials that enrolled patients with mRCC treated with (1) nivolumab/ipilimumab (nivo/ipi) +/- CBM588 and (2) cabozantinib/nivolumab (cabo/nivo) +/- CBM588... Supplementation with CBM588 leads to a marked correction of gut dysbiosis and prevents the depletion of species previously associated with ICI response (i.e., Eubacterium siraeum). These findings provide a plausible mechanism for the enhanced clinical outcome with CBM588 now seen across two small, randomized trials. A phase III study is planned within the cooperative groups to evaluate the clinical activity and gut microbiome modulation capacity of CBM588 in combination with ICIs in mRCC."

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

Impact of CBM588 on Gut Microbiome Composition and Dysbiosis in Patients Receiving Frontline Immune Checkpoint Inhibitor (ICI) Combinations for Metastatic Renal Cell Carcinoma (mRCC) (KCRS 2024) - "We examined the impact of CBM588 on gut microbiome composition in a combined cohort of these two studies to further investigate its impact on gut microbiome Methods We analyzed stool samples from two phase I randomized clinical trials that enrolled patients with mRCC treated with (1) nivolumab/ipilimumab (nivo/ipi) +/- CBM588 and (2) cabozantinib/nivolumab (cabo/nivo) +/- CBM588...These findings provide a plausible mechanism for the enhanced clinical outcome with CBM588 now seen across two small, randomized trials. A phase III study is planned within the cooperative groups to evaluate the clinical activity and gut microbiome modulation capacity of CBM588 in combination with ICIs in mRCC."

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

Impact of microbiome modulation on serum cytokine profile in a randomized, phase I trial of cabozantinib/nivolumab (cabo/nivo) with or without CBM588 in pts with metastatic renal cell carcinoma (mRCC) (KCRS 2024) - "Conclusions Taken together with our previous study evaluating nivolumab/ ipilimumab with CBM588 (Dizman et al Nat Med 2022), these results suggest that the augmented clinical outcome seen with the addition of CBM588 to cabo/nivo may be related to systemic immunomodulation. Combined analyses of the cohorts across studies are planned."

Clinical • Metastases • P1 data • Genito-urinary Cancer • Immunology • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CCL11 • CD4 • CD8 • CSF2 • IFNG • IL12A • IL13

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

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

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

Microbial Dysbiosis as a Determinant of Clinical Outcomes with CBM588 in Metastatic Renal Cell Carcinoma (mRCC) (EIKCS 2026) - "Our findings reinforce the growing body of evidence linking dysbiosis and outcomes with ICI-based treatments in mRCC and offer insights into its backbone-dependent behavior as a biomarker."

Clinical • Clinical data • Dysbiosis • Metastases • Genito-urinary Cancer • Renal Cell Carcinoma

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

Microbial dysbiosis as predictor of benefit from CBM588 as an adjunct to immune checkpoint blockade (ICB)–based first line therapies in metastatic renal cell carcinoma (mRCC). (ASCO 2026) - P1 | "Notably, S score was associated with response to SOC+CBM588 among patients who received nivolumab/ipilimumab backbone (median S score 0.668 in response vs 0.540 in no response, p = 0.046), while no such association was observed in patients treated with nivolumab/cabozantinib backbone (median S score 0.681 vs 0.821, p = 0.554, respectively). Addition of CBM588 to ICB-based first-line combinations conferred a disproportionately greater benefit in patients with a dysbiotic stool phenotype, underscoring actionability of TOPOSCORE as a potential predictive biomarker in this setting. The upcoming phase III randomized placebo-controlled BIOFRONT trial will assess clinical activity of CBM588 and advance microbiome-based predictive biomarker development in mRCC."

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

A Decade of Screening and Treating Helicobacter pylori Infection Among First-Year High School Students in Kyoto, Japan: Annual Trends in Infection, Consultation, and Eradication Success Rates (2015-2023). (PubMed, Helicobacter) - "The prospective adolescent screen-and-treat program demonstrated a significant decrease in H. pylori infection rates among first-year high school students over the decade. While the safety and efficacy of the PAM-based eradication regimen were verified, declining medical consultation rates present a continuous challenge for public health implementation."

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

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

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Adding a Live Biotherapeutic Product (CBM588) to Pembrolizumab for the Treatment of Renal Cell Cancer After Surgery (clinicaltrials.gov) - P2 | N=62 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Initiation date: May 2026 ➔ Jan 2027

Enrollment open • Trial initiation date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CXCL8