Previous studies have suggested that the gut microbiome influences the response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product that we postulated could augment CPI response through modulation of the gut microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive patients with metastatic renal cell carcinoma with clear cell and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 to receive nivolumab and ipilimumab with or without daily oral CBM588, respectively. Stool metagenomic sequencing was performed at multiple timepoints. The primary endpoint to compare the relative abundance of Bifidobacterium spp. at baseline and at 12 weeks was not met, and no significant differences in Bifidobacterium spp. or Shannon index associated with the addition of CBM588 to nivolumab–ipilimumab were detected. Secondary endpoints included response rate, progression-free survival (PFS) and toxicity. PFS was significantly longer in patients receiving nivolumab–ipilimumab with CBM588 than without (12.7 months versus 2.5 months, hazard ratio 0.15, 95% confidence interval 0.05–0.47, P = 0.001). Although not statistically significant, the response rate was also higher in patients receiving CBM588 (58% versus 20%, P = 0.06). No significant difference in toxicity was observed between the study arms. The data suggest that CBM588 appears to enhance the clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab–ipilimumab. Larger studies are warranted to confirm this clinical observation and elucidate the mechanism of action and the effects on microbiome and immune compartments.

clinicaltrials.gov Identifier: NCT00619918.

4513 Background: Recent evidence suggests that the gut microbiome is a potent mediator of immune checkpoint inhibitor (ICI) activity in metastatic renal cell carcinoma (mRCC), with both specific bacterial species and cumulative microbial diversity driving response (Routy et al Science 2018; Salgia et al Eur Urol 2020). We examined whether the butyrate-producing bacterium Clostridium butyricum, the key constituent of CBM-588, could modulate the gut microbiome in patients (pts) with mRCC receiving nivolumab/ipilimumab (N/I) and secondarily improve clinical outcome. Methods: An open-label, randomized study was conducted, with key eligibility criteria including confirmed clear cell and/or sarcomatoid mRCC, intermediate/poor risk by IMDC criteria and no systemic therapy for metastatic disease. Patients were randomized 2:1 to receive either N/I+CBM-588 or N/I alone. N/I was dosed at 3 mg/kg and 1 mg/kg IV every 3 weeks for 12 weeks, followed by N at 480 mg IV every 4 weeks. CBM-588 was dosed orally at 80 mg bid. Stool was collected for bacteriomic profiling at baseline and 12 weeks. Metagenomic sequencing was employed using previously published methods (Dizman et al Cancer Med 2020). The primary endpoint of the study was change in Bifidobacterium spp. from baseline to week 12. Secondary endpoints included change in microbial diversity and clinical outcomes including response rate (RR) and progression-free survival (PFS). Results: 30 pts were randomized between April 2019 and Nov 2020; 1 pt was excluded after genomic sequencing clarified a diagnosis of sarcoma. Among 29 evaluable patients (21:8 M:F), median age was 66, 10 pts (34%) had sarcomatoid features and 24 pts (83%) were intermediate risk. Metagenomic sequencing of paired stool specimens showed an 8-fold increase in B. bifidum and a 6-fold increase in B. adolescentis in pts receiving N/I+CBM-588 from baseline to week 12. C. butyricum was detected only in pts receiving CBM-588. Pathogenic species (e.g., Escherichia. coli and Klebsiella spp.) were more prevalent in pts not receiving CBM-588. RR was significantly higher among pts receiving N/I+CBM-588 vs N/I alone (59% vs 11%; P = 0.024). Median PFS was also prolonged with the addition of CBM-588 to N/I (NR vs 11 weeks; P < 0.001). No significant difference in grade 3/4 toxicities were observed between study arms. Conclusions: This is the first randomized, prospective study to suggest enhancement of ICI response with a live bacterial product. The observed clinical impact is corroborated by biologic findings supporting gut modulation by CBM-588. Clinical trial information: NCT03829111.

Background The effect of incorporating mobile technology to support participants’ lifestyle change and weight loss in medical group visits has not been well studied in a safety‐net setting. Rationale and Design Thus, the rationale of the current study was to examine the effect of text messaging in a medical group visit, and test the effect of two texting programs (12 weeks and 20 weeks), compared to those who did not receive text‐messaging in the Preventing Obesity With Eating Right (POWER) group visit program. The primary outcome was weight loss. Results We found that those enrolled in the 20‐week and 12‐week texting programs attended more group visit sessions than those enrolled in the POWER group only (p < 0.001). Both POWER and POWER + 20‐week texting groups had a significant reduction in weight at their final group visit compared to their baseline (POWER, 114 ± 27 kg vs. 112 ± 26 kg, p < 0.001; POWER + 20‐week texting, 111 ± 28 kg vs. 109 ± 28 kg, p < 0.01), but not the 12‐week texting group (114 ± 29 kg vs. 113 ± 29 kg, p = 0.22), with no differences between the groups. The number of group visits was correlated with a decrease in weight (rs = 0.12, p < 0.05). Conclusion In conclusion, text messaging programs led to more attendance in the medical group visits, but not greater weight loss or reduction in HbA1c than the POWER group obesity program alone. Further studies are needed to maximize the beneficial effects of texting programs in medical group visits in underserved minority populations.