This phase II trial compares the effect of adding a Live Biotherapeutic Product called CBM588 to pembrolizumab versus pembrolizumab alone in preventing return of disease (recurrence) after surgery for patients with renal cell cancer. Pembrolizumab is an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pembrolizumab is approved for the treatment of renal cell cancer after surgery. Research has shown that changes to the composition of the healthy bacteria in the body (the microbiome), may improve a patient's response to treatment with immunotherapy. CBM588, a Live Biotherapeutic Product (LBP) containing a bacteria called Clostridium butyricum, has been shown to improve outcomes in patients treated with immunotherapy for other types of cancer. Adding CBM588 to treatment with pembrolizumab after surgery may cause changes in the microbiome that improve patient response to treatment and reduce disease recurrence, compared to pembrolizumab alone.
Be willing and able to provide informed consent for the trial
Histological confirmation of renal cell carcinoma (RCC) with a clear-cell or sarcomatoid component
Pathologic stage of pT2, G4 or sarcomatoid, N0M0; pT3, any grade, N0M0; pT4, any grade, N0M0; pTany, any grade, N+M0; or M1 no evidence of disease (NED) after resection
No prior systemic immunotherapy for RCC
Prior radiation or anti-PD1, anti-PDL1, or anti-CTLA-4 therapy for RCC
Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
Baseline pulse oximetry less than 92% "on room air"
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Clostridium butyricum CBM588 Strain
DrugGiven PO
Computed Tomography
Procedure/SurgeryUndergo CT
Pembrolizumab
Biological/VaccineGiven IV
Change in interleukin (IL)-12 levels
A two-sample t-test will be used to test the difference in the changes in IL-12 production for the two treatment arms. A Wilcoxon rank-sum test will be used if the changes are not normally distributed (p\< 0.05 by a Shapiro-Wilks test).
Recurrence-free survival (RFS)
RFS will be estimated by the Kaplan-Meier method. Median RFS and landmark RFS rates (e.g., 1-year and 2-year RFS) will be calculated with confidence intervals. Log-rank test will be used to compare the distribution between groups. Cox proportional hazards model will be used to estimate hazard ratios with 95% confidence intervals.
Overall survival (OS)
OS will be estimated by the Kaplan-Meier method. Median OS and landmark OS rates (e.g., 1-year and 2-year OS) will be calculated with confidence intervals. Log-rank test will be used to compare the distribution between groups. Cox proportional hazards model will be used to estimate hazard ratios with 95% confidence intervals.
Shannon diversity index
A comparison of the Shannon diversity index (a measure of microbial diversity) from baseline to week 12 will be conducted.
Proportion of circulating regulatory T cells (Tregs)
Will estimate the proportion of Tregs in the blood.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
