CBM588 + Nivolumab + Ipilimumab for Advanced Kidney Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Osel, Inc.
Must not be taking: Probiotics, Corticosteroids, others
Disqualifiers: Interstitial lung disease, Brain metastases, others
No Placebo Group
Breakthrough Therapy
Trial Summary
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.
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.
12345Is 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.
26789What 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.
1291011Eligibility 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
+12 more
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
+22 more
Trial 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)
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (CBM588 capsules, nivolumab, ipilimumab)Experimental Treatment7 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
Osel, Inc.Lead Sponsor
Miyarisan Pharmaceuticals, Co., Ltd.Collaborator
City of Hope Medical CenterCollaborator
National Cancer Institute (NCI)Collaborator
References
Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. [2022]Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.
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]Targeting the programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) pathways using the combination immune checkpoint inhibitors (ICI) nivolumab and ipilimumab is an approved frontline therapy for patients with metastatic clear-cell renal cell carcinoma (mccRCC). Certain populations pose clinical challenges due to exclusion from large clinical trials that established the safety and efficacy of these treatments, including patients with end stage renal disease (ESRD). While there are reports successfully administering single-agent ICI in patients with ESRD, we present herein a case of safe and effective use of combination nivolumab plus ipilimumab in a 53-year-old man with mccRCC with sarcomatoid dedifferentiation and ESRD on hemodialysis.
Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]Nivolumab plus ipilimumab achieves higher response rates than previously reported for nivolumab alone.
The Evolving Landscape of Immunotherapy-Based Combinations for Frontline Treatment of Advanced Renal Cell Carcinoma. [2023]Insights into the biology of advanced renal cell carcinoma (aRCC) and the development of agents targeting the vascular endothelial growth factor (VEGF) pathway have positively impacted the outcomes for patients with aRCC. With the recent approval of the dual immune checkpoint inhibitors (ICIs), nivolumab and ipilimumab, by the U.S. Food and Drug Administration (USFDA), and the European Medicines Agency (EMA), the era of VEGF monotherapy for untreated aRCC appears to be coming to an end for patients with access to the combination therapy. The frontline treatment options for renal cell carcinoma are evolving rapidly and will lead to the approval of other combination immunotherapies-especially those with VEGF inhibitors. Here we review the clinical data for dual immune checkpoint inhibition with nivolumab plus ipilimumab as well as the emerging data for ICI plus VEGF inhibitor combinations and discuss the challenges these will pose for the clinical practitioner.
Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. [2021]Nivolumab is an immune checkpoint inhibitor targeting the programmed death-1 receptor that improves survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). In contrast to other tumor types that respond to immunotherapy, factors such as programmed death ligand-1 (PD-L1) status and tumor mutational burden show limited predictive utility in ccRCC. To address this gap, we report here the first molecular characterization of nivolumab response using paired index lesions, before and during treatment of metastatic ccRCC.
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]On the 15 November 2018, the Committee for Medicinal Products for Human Use adopted an extension to an existing indication for the use of nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of adult patients with intermediate/poor-risk advanced renal cell carcinoma (RCC). The approval was based on results from the Pivotal CA209214 study, a randomised, open-label, phase III study, comparing nivolumab +ipilimumab with sunitinib in subjects≥18 years of age with previously untreated advanced RCC (not amenable for surgery or radiotherapy) or metastatic RCC, with a clear-cell component. A total of 1096 patients were randomised in the trial, of which 847 patients had intermediate/poor-risk RCC and received either nivolumab (n=425) in combination with ipilimumab administered every 3 weeks for 4 doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks or sunitinib (n=422) administered orally for 4 weeks followed by 2 weeks off, every cycle. A statistically significant difference in overall survival (OS) was observed in the nivolumab + ipilimumab group compared with the sunitinib group in intermediate/poor-risk subjects (HR 0.63 (99.8% CI 0.44 to 0.89); stratified log-rank 2-sided p-value
Ipilimumab-induced immune-related renal failure--a case report. [2017]Ipilimumab is a fully human monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4 and has become the first immune checkpoint inhibitor to enter clinical practice, being recently approved for the treatment of metastatic melanoma. Immune toxicity due to ipilimumab causing colitis, hepatitis, dermatitis and hypophysitis is well-described. We report on a case of acute renal failure resolving rapidly with high-dose corticosteroid treatment highlighting the importance of vigilance for rarer immune-related toxicities as clinical experience with ipilimumab grows.
[Clinical Significance of Ipilimumab and the Combination Therapy as Immune Checkpoint Inhibitor]. [2019]Ipilimumab is the%ldquo;first in class"immune checkpoint inhibitors, which blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)to potentiate an anti-tumor effect of effector Tcells. Recently, the combination therapy with ipilimumab and anti- PD-1 antibody showed clinical benefit in some malignant tumors, advanced melanoma and renal cell cancer and so on. In this paper, we described clinical development of ipilimumab as the combination therapy including effectiveness and safety.
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]Nivolumab plus ipilimumab combination therapy is one of the standard therapies for untreated renal cell carcinoma patients with an International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor risk. We have previously reported the 1-year analysis results of the effectiveness and safety of nivolumab plus ipilimumab combination therapy in the real-world setting in Japan. Here, we report the effectiveness of nivolumab plus ipilimumab combination therapy and of second-line therapy, using 2-year analysis.
Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. [2022]The combination of ipilimumab plus nivolumab has been used as first-line therapy for metastatic renal cell carcinoma. While it is well known that hemodialysis patients have a higher rate of renal cell carcinoma compared to the general population, no reports have described the safety of ipilimumab-nivolumab in metastatic renal cell carcinoma patients on hemodialysis.
Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. [2023]Combined immune checkpoint blockade with nivolumab and ipilimumab is standard therapy for the treatment of patients with previously untreated advanced renal cell carcinoma who are at intermediate or poor risk. However, data about the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in patients on hemodialysis are limited. Renal function has no known clinically important effects on the pharmacokinetics and clearance of nivolumab and ipilimumab. Further, most immune-related adverse events in patients on hemodialysis are thought to be manageable with the same treatments applied in patients with normal renal function. We present a case of advanced clear-cell renal cell carcinoma in a patient on hemodialysis who received combined immune checkpoint blockade with nivolumab and ipilimumab and who showed no evident signs of immune-related adverse events. Here, we confirm the safety and efficacy of combined immune checkpoint blockade with nivolumab and ipilimumab in a patient on hemodialysis.