Microbiome-based therapy shows promise in solid tumors, including ccRCC

The combination of BMC128, a live bacterial consortium of 4 bacterial strains, and nivolumab demonstrated a manageable safety profile and preliminary anti-tumor effects in patients with clear cell renal cell carcinoma (ccRCC), non-small cell lung cancer (NSCLC), and cutaneous melanoma, according to preliminary findings from a phase 1 trial (NCT05354102) presented at the 2024 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

At the time of data report, 55% of patients had demonstrated sustained clinical benefit with the combination treatment.

"The positive trends emerging from the ongoing phase 1 trial of BMC128, particularly in combination with nivolumab, underscore the transformative potential of microbiome-based therapeutics in oncology,” said Gal Markel, MD, PhD, MBA, in a news release on the findings.² Markel is the director of the Davidoff Cancer Center at Rabin Medical Center as well as a member of Biomica’s Scientific Advisory Board.

For the study, all patients underwent depletion with antibiotics, induction with BMC128 monotherapy, and combination treatment followed by nivolumab monotherapy.

Overall, no serious adverse events (SAEs) related to BMC128 were reported. In total, 2 patients experienced minor AEs that the investigators characterized as potentially related to the investigational agent.

Regarding efficacy, encouraging clinical signals were noted in 72% of refractory cases. Specifically, all patients with ccRCC and 60% of patients with NSCLC demonstrated positive clinical outcomes.

In total, 1 patient in the study achieved a partial response on imaging per RECIST v1.1, which remains ongoing in the trial. Stable disease was achieved in 64% of patients, with sustained benefits lasting beyond the first imaging assessment.

At the time of data report, 55% of patients had demonstrated sustained clinical benefit with the combination treatment. Notable durations of response have exceeded 16 weeks, and 1 patient’s response has exceeding 80 weeks.

In total, the first-in-human, open-label study included 12 patients, of whom 6 had ccRCC, 5 had NSCLC-adenocarcinoma, and 1 had cutaneous melanoma. All patients included in the study had previously progressed on PD-1/PD-L1 inhibitors.

In the study, patients received oral BMC128 at the dose level of 4*108 live cells/strain daily in combination with 480mg nivolumab every 4 weeks. The primary outcome measure for the study is the number and severity of drug-related treatment-emergent AEs. The secondary outcome measure is the clinical effects of the combination treatment, consisting of the objective response rate (partial responses plus complete responses), clinical benefit rate, and the duration of response.³

The study remains ongoing, with expected completion in November 2025.

Markel added in the news release,² “These findings bring hope to patients contending with refractory RCC, NSCLC, and melanoma, envisioning a future where innovative treatments like BMC128 could provide meaningful solutions to longstanding challenges in cancer care. Additionally, the observed cross-cancer effectiveness hints at BMC128's broad applicability across different cancer types, further solidifying its significance in the field of oncology. The demonstrated safety profile thus far, alongside the encouraging clinical benefits including response rate and notable durability, accentuates the potential efficacy of BMC128 in addressing the unmet needs of patients grappling with these malignancies. These initial results mark a significant advancement, reflecting our steadfast commitment to pioneering innovative solutions that address critical unmet needs in oncology."

According to the study authors, a phase 2 trial of BMC128 is expected to be initiated in late 2024.

References

1. Perets R, Meshner S, Tirosh O, et al. Preliminary results from a FIH, open-label phase 1 study with BMC128, a rationally designed live bacterial consortium, in combination with nivolumab. J Clin Oncol. 2024;42(suppl 16);8631. doi:10.1200/JCO.2024.42.16_suppl.8631

2. Biomica presents positive clinical data update from ongoing phase 1 trial of microbiome-based therapeutic, BMC128, for refractory RCC, NSCLC & melanoma. News release. Biomica Ltd. May 23, 2024. Accessed June 17, 2024. https://www.prnewswire.com/news-releases/biomica-presents-positive-clinical-data-update-from-ongoing-phase-1-trial-of-microbiome-based-therapeutic-bmc128-for-refractory-rcc-nsclc--melanoma-302154259.html

3. A first-in-human (FIH) combination treatment study with a single dose level of BMC128. ClinicalTrials.gov. Last updated May 7, 2024. Accessed June 17, 2024. https://www.clinicaltrials.gov/study/NCT05354102