Nivolumab + Ipilimumab for Kidney Cancer

Not yet recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Probiotics, Antibiotics, Corticosteroids, others

Disqualifiers: Cardiac disease, Lung disease, Intestinal disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 25

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests the safety and effectiveness of combining two immunotherapy drugs, nivolumab and ipilimumab, with a bacterial treatment called EXL01 for treating kidney cancer that has spread. The goal is to determine if EXL01 can enhance the immune system's ability to fight cancer by influencing gut bacteria. The trial includes two groups: one receiving nivolumab and ipilimumab alone, and the other receiving the two drugs with EXL01. It seeks participants with advanced or metastatic kidney cancer who have not previously received these specific immunotherapy drugs. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this novel combination therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use probiotics, prebiotics, or certain supplements two weeks before and during the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that the combination of nivolumab and ipilimumab is generally safe for patients with advanced kidney cancer. Studies have found that while up to 20% of patients might experience disease progression early on, many others benefit from long-lasting effects. This combination also reduces the risk of death by about 28% compared to other treatments.

The current trial for EXL01, a live biotherapeutic product, is in its early stages. The main goal is to assess its safety when used with nivolumab and ipilimumab. Early-phase trials often provide limited safety information, but they are crucial for determining a treatment's safety for people.

In summary, nivolumab and ipilimumab have a strong safety record, while EXL01 is still undergoing safety testing in combination with them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for kidney cancer because they combine two powerful immunotherapy drugs, nivolumab and ipilimumab, which work together to boost the immune system's ability to fight cancer. Unlike traditional treatments like surgery or targeted therapies, this combination specifically enhances the body's immune response to attack cancer cells more effectively. Additionally, the experimental treatment arm introduces EXL01, an oral medication that might further amplify the immune response, potentially offering a new avenue for improved outcomes. This approach could represent a significant advancement by not only targeting the cancer but also enhancing patients' overall immune surveillance.

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

Research has shown that using nivolumab and ipilimumab together can be promising for treating advanced kidney cancer. About 40% of patients experience long-term benefits, while around 20% see their disease worsen early on. Another study found that these drugs lowered the risk of death by 28% compared to a common treatment. In this trial, participants in Arm A will receive a combination of nivolumab, ipilimumab, and EXL01, a beneficial bacteria that might enhance the immune system's ability to fight cancer. Participants in Arm B will receive nivolumab and ipilimumab without EXL01. This combination aims to boost the body's natural defenses against cancer spread. ^{1 2 3 4 5}

Who Is on the Research Team?

Sumanta K Pal

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic renal cell cancer, which means their kidney cancer has spread to other parts of the body. Participants should meet certain health standards but specific inclusion criteria are not provided here.

Inclusion Criteria

I haven't had systemic therapy for kidney cancer, except under certain conditions.

Agreement to use contraception during and after the study period

Normal coagulation parameters

Exclusion Criteria

I do not have unstable heart conditions.

I have had major surgery recently.

Inability to comply with all study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive nivolumab and ipilimumab with or without EXL01 in cycles. Cycles 1-4 repeat every 21 days, and cycles 5+ repeat every 28 days.

Up to 2 years

Every 21-28 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits every 3 months.

Up to 2 years

Every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• EXL01
• Ipilimumab
• Nivolumab

Trial Overview The trial is testing the safety and effectiveness of two immunotherapy drugs, Nivolumab and Ipilimumab, with or without a new treatment called EXL01. It's a phase I study to see if adding EXL01 improves patient responses by changing gut bacteria.

How Is the Trial Designed?

Group I: Arm A (nivolumab, ipilimumab, EXL01) Experimental Treatment 7 Interventions

CYCLES 1-4: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle and receive EXL01 PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CYCLES 5+: Patients continue receiving nivolumab IV over 30 minutes on day 1 of each cycle and EXL01 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and collection of blood samples throughout the study. Patients may undergo MRI at screening and may undergo bone scan as clinically indicated.

Group II: Arm B (nivolumab, ipilimumab) Active Control 6 Interventions

CYCLES 1-4: Patients receive 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 in the absence of disease progression or unacceptable toxicity. CYCLES 5+: Patients continue receiving nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and collection of blood samples throughout the study. Patients may undergo MRI at screening and may undergo bone scan as clinically indicated.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39705641/

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT07128680

NCT07128680 | Immunotherapy (Nivolumab and ... This phase I trial tests the safety and effectiveness of nivolumab and ipilimumab with and without EXL01 for the treatment of renal cell ...

3. cancerdiagnosisprognosis.org cancerdiagnosisprognosis.org/article/500/analysis-of-early-progression-in-advanced-renal-cell-carcinoma-treated-with-nivolumab-plus-ipilimumab

Analysis of Early Progression in Advanced Renal Cell ... Approximately 40% of patients treated with NIVO + IPI experience a durable response, although 20% face early disease progression (EDP) (5).

4. news.bms.com news.bms.com/news/details/2024/Eight-Year-Data-for-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Continue-to-Demonstrate-Longest-Survival-Benefit-vs.-Sunitinib-Reported-in-Patients-with-Previously-Untreated-Advanced-or-Metastatic-Renal-Cell-Carcinoma/default.aspx

Eight-Year Data for Opdivo (nivolumab) Plus Yervoy ... Patients with previously untreated advanced or metastatic renal cell carcinoma treated with Opdivo plus Yervoy experienced a 28% reduction in the risk of death ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38251783/

Real-world outcomes of nivolumab plus ipilimumab ... Regarding an effectiveness profile, median progression-free survival, time to treatment failure and overall survival were 9.01, 12.5 and 49.0 ...