Immunotherapy (Nivolumab and Ipilimumab) With and Without a Live Biotherapeutic Product (EXL01) for the Treatment of Metastatic Renal Cell Cancer
A Randomized Study of Nivolumab and Ipilimumab With and Without EXL01 in First-Line Treatment of Metastatic Renal Cell Carcinoma (mRCC)
3 other identifiers
interventional
33
1 country
2
Brief Summary
This phase I trial tests the safety and effectiveness of nivolumab and ipilimumab with and without EXL01 for the treatment of renal cell cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. EXL01 is a live biotherapeutic product containing a strain of bacteria called Faecalibacterium prausnitzii. It may enhance a patient's response to treatment with immune checkpoint inhibitors like nivolumab and ipilimumab by altering the composition of the bacteria in the gut. Adding EXL01 to treatment with nivolumab and ipilimumab may be safe and more effective than giving nivolumab and ipilimumab alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2026
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 14, 2025
CompletedFirst Posted
Study publicly available on registry
August 19, 2025
CompletedStudy Start
First participant enrolled
April 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 25, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 25, 2028
February 27, 2026
February 1, 2026
2.4 years
August 14, 2025
February 25, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Change in plasma IFNγ
IFNγ plasma concentration will be analyzed using a 2-sample t-test if normality assumptions are met; otherwise, the Wilcoxon rank sum test will be applied.
At baseline and week 13
Secondary Outcomes (5)
Incidence of grade ≥ 3 adverse events (AEs)
Up to 30 days after last dose of treatment
Best overall response
Up to 2 years
Duration of response
From first documented complete response or partial response until disease progression or death, assessed up to 2 years
Progression free survival
From start of treatment to time of progressive disease or death, assessed up to 2 years
Overall survival
From start of treatment to death from any cause, assessed up to 2 years
Study Arms (2)
Arm A (nivolumab, ipilimumab, EXL01)
EXPERIMENTALCYCLES 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.
Arm B (nivolumab, ipilimumab)
ACTIVE COMPARATORCYCLES 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.
Interventions
Undergo bone scan
Undergo collection of blood samples
Undergo CT
Given IV
Undergo MRI
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with study principal investigator (PI) approval
- Age: ≥ 18 years at time of signing informed consent
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Life expectancy \> 3 months
- Histologically confirmed renal cell carcinoma with clear cell renal cell carcinoma component with or without sarcomatoid component
- Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) renal cell carcinoma with any disease risk disease by International Metastatic RCC Database Consortium (IMDC) criteria (good-, intermediate- or poor-risk)
- No prior systemic therapy for RCC with the following exception:
- One prior adjuvant or neoadjuvant therapy for completely resectable RCC if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy, provided that the patient has fully recovered from acute toxic effects to prior anti-cancer therapy
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
- Platelets ≥ 100,000/mm\^3
- +19 more criteria
You may not qualify if:
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- Current use, or intent to use probiotics, prebiotics, bacterial fortified foods and other natural supplements ≤ 2 week prior to treatment initiation and during the period of treatment
- Any botanical preparation (e.g. herbal supplements or traditional Chinese medicines) intended to treat the disease under study or provide supportive care
- Fecal microbiota transplant within 3 months prior to screening
- Note: Patients must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention
- Patients requiring chronic antibiotic therapy at the time of study enrollment
- Unstable cardiac disease as defined by one of the following:
- Cardiac events such as myocardial infarction (MI) within the past 6 months
- NYHA (New York Heart Association) heart failure class III-IV
- Uncontrolled atrial fibrillation or hypertension
- Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
- Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
- Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
- Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Patients must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
City of Hope Medical Center
Duarte, California, 91010, United States
City of Hope Medical Center
Irvine, California, 92618, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sumanta K Pal
City of Hope Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 14, 2025
First Posted
August 19, 2025
Study Start
April 1, 2026
Primary Completion (Estimated)
August 25, 2028
Study Completion (Estimated)
August 25, 2028
Last Updated
February 27, 2026
Record last verified: 2026-02