A Randomized Study of Nivolumab and Ipilimumab With and Without EXL01 in First-Line Treatment of Metastatic Renal Cell Carcinoma (mRCC)
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.
• 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
⁃ NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
• Hemoglobin ≥ 9g/dL
⁃ NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (except for subjects with Gilbert Syndrome, who may have total bilirubin up to 3.0 mg/dL)
• Aspartate aminotransferase (AST) ≤ 3.0 x ULN
• Alanine aminotransferase (ALT) ≤ x ULN
• Creatinine clearance of ≥ 30 mL/min per 24-hour urine test or the Cockcroft-Gault formula or serum creatinine \< 1.5 x upper limit of normal (ULN)
• If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN
• If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
• If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
• If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
• If seropositive for HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV), nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Meets other institutional and federal requirements for infectious disease titer requirements
⁃ Note infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test within 72 hours of study start
⁃ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of nivolumab or ipilimumab for women with childbearing potential, and 5 months after the last dose of nivolumab or ipilimumab for men. For EXL01, female participants should continue contraception for 30 days after the last dose
• Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating \[FSH\] level \> 40 mIU/mL to confirm menopause).
⁃ Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site