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

Trial Summary

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.

What data supports the effectiveness of the drug combination CBM588, Nivolumab, and Ipilimumab for advanced kidney cancer?

Research shows that the combination of nivolumab and ipilimumab is effective for treating advanced kidney cancer, with studies indicating it produces positive responses in patients. This combination is approved as a frontline therapy for metastatic clear-cell renal cell carcinoma, suggesting its potential effectiveness when used with CBM588. ^{1 2 3 4 5}

Is the combination of CBM588, Nivolumab, and Ipilimumab safe for humans?

Nivolumab and Ipilimumab have been used together safely in patients with advanced kidney cancer, although they can cause side effects like immune-related issues affecting organs such as the kidneys, skin, and liver. In some cases, these side effects can be managed with medications like corticosteroids. There is less information available about the safety of CBM588 in this combination. ^{2 6 7 8 9}

What makes the CBM588 + Nivolumab + Ipilimumab treatment unique for advanced kidney cancer?

The combination of CBM588 with nivolumab and ipilimumab is unique because it adds a probiotic (CBM588) to the standard immune checkpoint inhibitors (nivolumab and ipilimumab), potentially enhancing the immune response against advanced kidney cancer. ^{1 2 9 10 11}

What is the purpose of this trial?

This phase I trial tests the safety, side effects, best dose, and effectiveness of CBM588 in combination with nivolumab and ipilimumab in treating patients with kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). CBM588 is a live biotherapeutic that may help improve the effects of immunotherapy. Nivolumab and ipilimumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread by enhancing the ability of the body's immune cells to attack tumor cells. CBM588 in combination with nivolumab and ipilimumab may be safe, tolerable, and/or effective in treating patients with advanced stage kidney cancer.

Research Team

Alex Chehrazi-Raffle, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. [2022]

2. England 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Evolving Landscape of Immunotherapy-Based Combinations for Frontline Treatment of Advanced Renal Cell Carcinoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. [2021]

6. England 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. [2021]

7. Greece pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced immune-related renal failure--a case report. [2017]

8. Japan pubmed.ncbi.nlm.nih.gov

[Clinical Significance of Ipilimumab and the Combination Therapy as Immune Checkpoint Inhibitor]. [2019]

9. England 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). [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. [2023]