CBM588 + Nivolumab/Ipilimumab for Kidney Cancer

Overseen By Sumanta K. Pal, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Osel, Inc.

Must not be taking: Probiotics, Yogurt

Disqualifiers: Interstitial lung disease, Brain metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 12

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment combination for advanced kidney cancer. It involves taking CBM588 capsules (a probiotic) with two immune-boosting drugs, nivolumab and ipilimumab. Participants will help researchers determine the best dose of CBM588 to use with the other treatments. Ideal participants have advanced kidney cancer that has not been treated with systemic therapy and cannot be cured with surgery or radiation. 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.

Will I have to stop taking my current medications?

The trial information 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. It's best to discuss your current medications with the study team.

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

Research has shown that CBM588, when combined with drugs like nivolumab and ipilimumab, might improve outcomes for kidney cancer patients. In studies, CBM588 has been tested with other cancer treatments and has shown some side effects. For instance, one study found that 45% of patients experienced serious side effects related to the treatment, compared to 40% in the group that did not receive CBM588.

Nivolumab and ipilimumab are well-known cancer treatments that generally work well with the body. They help the immune system fight cancer but can also cause side effects. Common side effects include fatigue and skin reactions, while more serious ones can affect the immune system.

Overall, while CBM588 appears promising, its side effects are still under investigation. This trial aims to determine the safest dose when combined with nivolumab and ipilimumab. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

CBM588 is unique because it combines a probiotic approach with dual immune checkpoint inhibitors, nivolumab and ipilimumab, for treating kidney cancer. Unlike standard treatments that mainly focus on targeting cancer cells directly, CBM588 works by potentially modulating the gut microbiome to enhance the body's immune response against cancer. Researchers are excited about CBM588 because it represents a novel mechanism of action that could improve the effectiveness of existing immunotherapy options and offer a new avenue for managing kidney cancer.

What evidence suggests that CBM588 in combination with nivolumab and ipilimumab could be effective for kidney cancer?

Research has shown that adding CBM588 to the treatment combination of nivolumab and ipilimumab can benefit kidney cancer patients. In one study, patients who received CBM588 with these drugs lived for a median of 55 months, compared to 39 months for those without CBM588. Another study found that the time during which the cancer did not worsen was significantly longer with CBM588, lasting 36.4 months compared to just 2.5 months with the drugs alone. This trial will evaluate CBM588 in combination with nivolumab and ipilimumab. These findings suggest that CBM588 may enhance the effectiveness of standard immunotherapy in treating kidney cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Alexander Chehrazi-Raffle, M.D.

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer, specifically Renal Cell Carcinoma. Participants must be able to take oral medication and have not been treated with Nivolumab or Ipilimumab before. People who've had certain other treatments or health conditions that could interfere with the study are excluded.

Inclusion Criteria

Measurable disease by RECIST 1.1

I have recovered from the side effects of my previous cancer treatment.

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

I have or had lung inflammation that needed treatment.

I have recently had cancer treatment with drugs or radiation.

Noncompliance with study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of CBM588 in combination with nivolumab and ipilimumab to determine the maximum tolerated dose (MTD)

28 days

Regular visits for dose escalation monitoring

Dose Expansion

10 additional patients are enrolled at the MTD to further evaluate safety and efficacy

90 days

Regular visits for safety and efficacy evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Re-evaluation every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CBM588
• Ipilimumab
• Nivolumab

Trial Overview The study tests different doses of CBM588 capsules combined with standard doses of Nivolumab and Ipilimumab to find the highest dose patients can tolerate without severe side effects (MTD). After finding MTD, they'll expand the group to further check safety and how well it works.

How Is the Trial Designed?

Group I: CBM588 Capsules Experimental Treatment 3 Interventions

This will be a dose escalation study of CBM588 oral capsules at two potencies in combination with nivolumab and ipilimumab dual immune checkpoint therapy: 1x Capsule containing 4.0E+8 CFU/capsule; and 10x Capsule containing 4.0E+9 CFU/capsule. The dose escalation will begin with one 1x Capsule administered twice a day followed by three 1x Capsules b.i.d., and then one 10x Capsule b.i.d. until disease progression or dose limiting toxicity occurs.

Who Is Running the Clinical Trial?

Osel, Inc.

Lead Sponsor

Trials

7

Recruited

250+

City of Hope Comprehensive Cancer Center

Collaborator

Trials

6

Recruited

230+

Miyarisan Pharmaceutical Co., Ltd.

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

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, 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]

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]

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]

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]

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 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]

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]

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]

In a study of 18 patients with non-clear cell renal cell carcinoma (nccRCC) treated with ipilimumab plus nivolumab, 33.3% achieved partial responses, indicating that this combination therapy can be effective for this type of cancer.

However, the treatment was associated with significant toxicity, with 61.1% of patients experiencing treatment-related adverse events, including serious conditions like colitis and hepatotoxicity, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity of Ipilimumab Plus Nivolumab in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma. Gupta, R., Ornstein, MC., Li, H., et al.[2021]

Nivolumab, an immune-checkpoint inhibitor used to treat lung adenocarcinoma, can lead to autoimmune side effects, as demonstrated by a case of acute tubulointerstitial nephritis in a 67-year-old patient after three infusions.

The kidney biopsy revealed specific histological changes, including proliferation of certain immune cells, indicating that nivolumab can trigger significant immune responses that may affect organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings. Uchida, A., Watanabe, M., Nawata, A., 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]

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]

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. 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 ...

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. 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.

6. 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 ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.543

Cabozantinib (cabo) and nivolumab (nivo) with or without ... Grade 3 or higher treatment-related adverse events (TRAEs) were observed in 45% of the CBM588 arm compared to 40% in the control arm. The most ...