Preliminary results from a FIH, open-label phase 1 study with BMC128, a rationally designed live bacterial consortium, in combination with nivolumab.

Abstract

8631 Background: Immune-Checkpoint inhibitors (ICI) have transformed the treatment of solid tumors, specifically in cutaneous melanoma, clear cell renal cell carcinoma (ccRCC) and non-small cell lung cancer (NSCLC). Despite these advances, resistance to ICI eventually occurs in many patients. Recent reports have found that patients showing poor response to ICI are characterized by a reduced gut microbiome diversity, suggesting that the gut microbiome might affect immune activation by ICI. BMC128 is a live bacterial consortium of 4 bacterial strains designed to induce anti-tumor immune function when given in conjunction with ICI. These strains were identified by analyzing microbiome data obtained from NSCLC and ccRCC patients presenting varied responses to ICI, using a proprietary computational discovery platform enabling high-resolution functional microbiome analysis. In pre-clinical studies, treatment with BMC128 potentiated the efficacy of ICI in breast cancer and melanoma mouse models, reducing tumor volume, increasing the number of responders, and demonstrating an increase in infiltrating immunocytes: CD4, CD8 and NK cells. The aim of this study was to assess the safety and tolerability of BMC128 in combination with nivolumab. Methods: 12 patients with ccRCC, cutaneous melanoma and NSCLC-adenocarcinoma (EGFR/ALK wild-type) (6, 1 and 5 patients, respectively), who previously progressed on PD1/PDL-1 inhibitors were recruited to this FIH open label phase 1 study. Patients were treated with a daily oral dose of BMC128 4*108 live cells/ strain in combination with nivolumab 480mg q4weeks. The study treatment consisted of 4 stages: depletion with antibiotics, induction with BMC128 monotherapy, combination treatment, and nivolumab monotherapy. Results: No SAEs related to BMC128 were reported throughout the duration of the study. Two patients exhibited minor AEs that were potentially associated with BMC128. At the current time point, 4 out ofthe first 8 patients in the study showed SD and sustained benefit beyond the first imaging timepoint, following the combination treatment. Altogether demonstrating clinical benefit for a total of 16 weeks (2 patients), 24 weeks (1 patient), and 68 weeks (1 patient). Conclusions: BMC128 has demonstrated an excellent safety profile and preliminary beneficial clinical effect. A phase 2 study to investigate the efficacy of BMC128 is planned to be initiated in late 2024. Clinical trial information: NCT05354102 .