Cdactin-O (CBM588)

P=N/A, N=200, Completed, Liaquat University of Medical & Health Sciences

P1, N=30, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Dec 2023 | Trial primary completion date: Jun 2024 --> Dec 2023

Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab...Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546.

In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as Streptococcus salivarius, have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer...Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.

P1, N=28, Recruiting, Osel, Inc.

P1, N=28, Recruiting, City of Hope Medical Center

Conversely, blockade of interleukin-10 signaling preferentially enhanced the capacity of CD8+ T cells to secrete Interferon gamma when being cocultured with CBM588-primed lamina propria mononuclear cells of tumor-bearing mice. Our results demonstrate that CBM588-centered intervention can adequately improve intestinal homeostasis and efficiently overcome resistance to PD-1 blockade in mice.

P1, N=36, Active, not recruiting, City of Hope Medical Center | Trial primary completion date: Dec 2023 --> Dec 2024 | Trial completion date: Dec 2023 --> Dec 2024

Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy.

P1, N=30, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

P1, N=31, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

In total, 488 patients who received nivolumab therapy were included. In all cancers, no significant differences in treatment duration of nivolumab were observed between probiotic users and non-users (median 62.0 vs. 56.0, hazard ratio = 1.02, p = 0.825), whereas probiotic use, compared with non-use, in patients with gastric cancer was significantly associated with a longer duration of nivolumab treatment (55.0 vs. 31.0 days, hazard ratio = 0.69, p = 0.039). In conclusion, probiotics may improve the response to nivolumab and potentially prolong progression-free survival in patients with gastric cancer.

P1, N=31, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting

CBM588 contributes to the maintenance of intestinal microbiota diversity early after haematopoietic cell transplantation. Furthermore, CBM588 effectively reduced the cluster III microbiota at risk for acute GVHD and showed the potential for improved the prognosis. We are planning prospective investigations are required to test it.

There was no significant difference observed in clinically relevant genomic features across study arms. The clinical benefit from CBM-588 appears to be independent of tumor genomic characteristics. More extensive investigations are needed to characterize the determinants of benefit from CBM-588 supplementation.

P1, N=30, Recruiting, City of Hope Medical Center

Recently, we found that intestinal care using oral L‒glutamine‒ enriched supplement and probiotics including Lactobacillus casei Shirota supplement(Yakult®)and Clostridium butyricum MIYAIRI 588 strain(Miya‒BM®)could induce a strong anti‒tumor immune response through the induction of fully mature tertiary lymphoid structures in some pancreatic cancer patients who received 3 cycles of preoperative chemotherapy(gemcitabine 1,000 mg/m2 plus nab‒paclitaxel 125 mg/m2 on days 1, 8, and 15 of 28‒day cycle). In this review article, we discussed the role of intestinal care in the induction of fully mature tertiary lymphoid structures in cancer patients receiving chemotherapy.