CBM588 + Nivolumab + Ipilimumab for Advanced Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Osel, Inc.

Must not be taking: Probiotics, Corticosteroids, others

Disqualifiers: Interstitial lung disease, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for advanced kidney cancer that may have spread to other parts of the body. It combines CBM588, a live biotherapeutic, with two immunotherapy drugs, nivolumab and ipilimumab, to evaluate their combined effectiveness and determine the safest and most effective dose. The trial seeks participants with advanced kidney cancer who have not received previous systemic therapy for this condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use probiotics, yogurt, or bacterial fortified foods during the treatment period, and you must not have received any systemic anticancer therapy within 4 weeks before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using CBM588 with nivolumab and ipilimumab might be safe and manageable for people with advanced kidney cancer. Previous studies suggest that this combination could outperform other treatments.

CBM588 is a live biotherapeutic, using live bacteria to help the immune system fight cancer. Nivolumab and ipilimumab are drugs that assist the immune system in attacking cancer cells. Some studies indicate that adding CBM588 to these drugs improves patient response and delays cancer progression.

While these results are encouraging, it is important to note that this is an early-phase trial. Researchers are primarily assessing the treatment's safety and patient tolerance. So far, patients seem to tolerate the combination, but more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of CBM588, nivolumab, and ipilimumab for advanced kidney cancer because it introduces a novel approach to treatment. Most traditional therapies for this condition, like tyrosine kinase inhibitors, focus on blocking cancer growth signals, but this combo targets the immune system in a unique way. CBM588 is a probiotic that may enhance the immune-boosting effects of nivolumab and ipilimumab, which are immune checkpoint inhibitors that help the body recognize and attack cancer cells. This combination could potentially offer more robust and sustained immune responses against cancer, offering hope for improved outcomes compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for advanced kidney cancer?

Research shows that adding CBM588 to kidney cancer treatment may enhance the effectiveness of the immunotherapy drugs nivolumab and ipilimumab. In studies, patients who received CBM588 with nivolumab and ipilimumab experienced better outcomes. Specifically, they lived longer on average—55 months compared to 39 months with just nivolumab and ipilimumab. The period during which the cancer did not worsen was 36.4 months with the CBM588 combination, compared to only 2.5 months with nivolumab and ipilimumab alone. In this trial, participants will receive the combination of CBM588, nivolumab, and ipilimumab. Nivolumab and ipilimumab together have already been shown to reduce the risk of death by 28% in patients with advanced kidney cancer. This suggests that CBM588 might help the body fight cancer more effectively when used with these immunotherapy drugs. ^{3 6 7 8 9}

Who Is on the Research Team?

Alex Chehrazi-Raffle, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced kidney cancer that has spread. It's testing the safety and effectiveness of a new treatment combination.

Inclusion Criteria

Assent, when appropriate, will be obtained per institutional guidelines

Must meet specified blood count criteria

Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Exclusion Criteria

I can follow all the study's required procedures.

Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment

History of allergic reactions attributed to compounds of similar composition to study agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Patients receive CBM588 capsules orally twice daily, nivolumab intravenously over 30 minutes, and ipilimumab intravenously over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles.

12 weeks

4 visits (in-person)

Dose-Expansion Treatment

Patients receive CBM588 orally twice daily on days 1-28 and nivolumab intravenously on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ongoing until disease progression or unacceptable toxicity

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with annual follow-up visits.

Up to 3 years

Annual visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CBM588
• Ipilimumab
• Nivolumab

Trial Overview The trial examines CBM588, a probiotic, combined with two monoclonal antibodies, Nivolumab and Ipilimumab, to see if they can improve outcomes in advanced kidney cancer.

How Is the Trial Designed?

Group I: Treatment (CBM588 capsules, nivolumab, ipilimumab) Experimental Treatment 7 Interventions

Patients receive CBM588 PO BID on days 1-21, nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles. Patients then receive CBM588 PO BID on days 1-28 and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT, bone scan and blood sample collection throughout the study. Patients may optionally undergo MRI on study.

Who Is Running the Clinical Trial?

Osel, Inc.

Lead Sponsor

Trials

7

Recruited

250+

Miyarisan Pharmaceuticals, Co., Ltd.

Collaborator

Trials

1

Recruited

30+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A 73-year-old hemodialysis patient with metastatic renal cell carcinoma was treated with the combination of ipilimumab and nivolumab, which was administered safely without any adverse events.

This case suggests that ipilimumab-nivolumab can be a viable treatment option for metastatic renal cell carcinoma in patients on hemodialysis, a group that typically has limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. Iwaki, T., Niimi, A., Kano, M., et al.[2022]

In a study of 45 Japanese patients with untreated metastatic renal cell carcinoma, the combination therapy of nivolumab and ipilimumab showed a 41.5% objective response rate and a median progression-free survival of 17.8 months over a 2-year follow-up period.

The 2-year analysis indicated that nivolumab plus ipilimumab therapy's effectiveness aligns with previous studies, and second-line therapy following this combination also demonstrated a 20% objective response rate with a median progression-free survival of 9.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study). Kojima, T., Kato, R., Sazuka, T., et al.[2022]

A patient on hemodialysis with advanced clear-cell renal cell carcinoma successfully received combined immune checkpoint blockade therapy with nivolumab and ipilimumab, showing no significant immune-related adverse events.

This case supports the safety and efficacy of using nivolumab and ipilimumab in patients on hemodialysis, suggesting that renal function does not significantly impact the treatment's pharmacokinetics or safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. Kobayashi, Y., Arai, H., Honda, M.[2023]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

Ipilimumab, an immune checkpoint inhibitor approved for metastatic melanoma, can cause immune-related toxicities such as colitis, hepatitis, and dermatitis, but also rare effects like acute renal failure.

In a reported case, acute renal failure due to ipilimumab was successfully treated with high-dose corticosteroids, emphasizing the need for careful monitoring of less common side effects as more patients are treated with this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced immune-related renal failure--a case report. Forde, PM., Rock, K., Wilson, G., et al.[2017]

The combination of nivolumab and ipilimumab, which targets PD-1 and CTLA-4 pathways, is an approved frontline therapy for metastatic clear-cell renal cell carcinoma (mccRCC).

This case study demonstrates the safe and effective use of this combination therapy in a 53-year-old patient with mccRCC and end-stage renal disease (ESRD) on hemodialysis, highlighting its potential applicability in populations often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and effective use of nivolumab plus ipilimumab in a patient with metastatic clear-cell renal cell carcinoma with sarcomatoid dedifferentiation and end stage renal disease on hemodialysis. Shaw, LK., Wiele, AJ., Sircar, K., et al.[2022]

Ipilimumab is a pioneering immune checkpoint inhibitor that enhances the anti-tumor response of T cells by blocking CTLA-4, which is crucial for its mechanism of action against cancer.

Combining ipilimumab with anti-PD-1 antibodies has shown clinical benefits in treating advanced melanoma and renal cell cancer, indicating improved efficacy in these malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Significance of Ipilimumab and the Combination Therapy as Immune Checkpoint Inhibitor]. Muto, Y., Kitano, S.[2019]

Nivolumab, an immune checkpoint inhibitor, shows improved survival in some patients with metastatic clear cell renal cell carcinoma (ccRCC), but traditional predictive factors like PD-L1 status are not effective in this context.

The study identified that T-cell infiltration is positively associated with treatment response, while certain molecular pathways, such as the RIG-I-MDA5 pathway, may contribute to resistance in highly T-cell infiltrated tumors, suggesting new avenues for patient selection and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. Ross-Macdonald, P., Walsh, AM., Chasalow, SD., et al.[2021]

In a phase 3 trial involving 1096 patients with untreated advanced renal-cell carcinoma, nivolumab plus ipilimumab significantly improved overall survival rates (75% at 18 months) compared to sunitinib (60% at 18 months), indicating a more effective treatment option for patients with intermediate or poor prognostic risk.

The objective response rate was also higher with nivolumab plus ipilimumab (42%) compared to sunitinib (27%), although both treatments had a high incidence of treatment-related adverse events, with nivolumab plus ipilimumab showing a slightly lower rate of severe (grade 3 or 4) events (46% vs. 63%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. Motzer, RJ., Tannir, NM., McDermott, DF., et al.[2022]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

The approval of the dual immune checkpoint inhibitors nivolumab and ipilimumab marks a significant advancement in the treatment of advanced renal cell carcinoma (aRCC), moving away from traditional VEGF monotherapy.

Emerging data suggests that combining immune checkpoint inhibitors with VEGF inhibitors may further enhance treatment options for aRCC, indicating a shift towards more effective combination therapies in frontline treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Evolving Landscape of Immunotherapy-Based Combinations for Frontline Treatment of Advanced Renal Cell Carcinoma. Amin, A., Hammers, H.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4550

Long-term clinical outcomes with nivolumab/ipilimumab ... The median OS with nivolumab/ipilimumab with CBM588 was 55.0 (95% CI 10.5-75.5) months versus 39.0 (95% CI 23.7-54.3) months with nivolumab/ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9018425/

Nivolumab plus ipilimumab with or without live bacterial ... The data suggest that CBM588 appears to enhance the clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab– ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05122546

Study Details | NCT05122546 | CBM588 in Combination ... The primary aim of this study is to determine how CBM588 changes the microbiome of patients with metastatic renal cell carcinoma.

4. urotoday.com urotoday.com/conference-highlights/ikcs-2022/140540-ikcs-2022-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.html

IKCS 2022: Clinical Outcomes with Nivolumab/Ipilimumab ... At a median follow-up of 27.7 months, the median PFS was superior for the CBM588 combination – 36.4 months versus 2.5 months with ipilimumab + nivolumab doublet ...

5. nature.com nature.com/articles/s41591-024-03086-4

Cabozantinib and nivolumab with or without live bacterial ... Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06414642

CBM588 Capsules in Combination With Nivolumab and ... CBM588 in combination with nivolumab and ipilimumab may be safe, tolerable, and/or effective in treating patients with advanced stage kidney cancer. Detailed ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS611

Dose finding study of CBM588 in combination with ... The current study explores the use of CBM588, Clostridium butyricum MIYARI588, which has demonstrated the potential to enhance clinical outcomes ...

8. urotoday.com urotoday.com/video-lectures/journal-clubs/video/mediaitem/2631-nivolumab-ipilimumab-nivo-ipi-with-or-without-cbm588-in-metastatic-renal-cell-carcinoma-journal-club-christopher-wallis-zachary-klaassen.html

Nivolumab/Ipilimumab (Nivo/Ipi) with or Without CBM588 in ... ... Clostridium butyricum could improve outcomes among patients with advanced kidney cancer who are being treated with nivolumab and ipilimumab.

9. onclive.com onclive.com/view/nivolumab-ipilimumab-plus-cbm588-generates-superior-efficacy-in-metastatic-rcc

Nivolumab/Ipilimumab Plus CBM588 Generates Superior ... The addition of CBM588 to the combination of nivolumab and ipilimumab produced superior response rates and a progression-free survival benefit vs nivolumab ...