Meiji Holdings Co., Ltd. Highlights that Yogurt Containing Bacteria Metabolite Shows a Tendency Toward Higher Response When Added to Immune Checkpoint Inhibitor Therapy in People Living with Non-small Cell Lung Cancer

NSCLC is the most common type of lung cancer, making up about 80% to 85% of all lung cancer cases. ICIs, including anti–PD–1 antibodies, are widely used as therapeutic agents for many types of cancer including lung cancer. While these treatments can produce significant benefits in certain people, response rates are known to be approximately 20–30%. In recent years, growing attention has been given to strategies aimed at improving the therapeutic efficacy of ICIs by modulating the gut microbiota or administering probiotics.

Saitama Medical University previously identified a subset of Th1-like CCR6⁺ CD4⁺ T cells, termed Th7R, that is correlated with response to ICI therapy for NSCLC. Meanwhile, preclinical studies conducted by Juntendo University, Meiji and other collaborating institutions demonstrated that R-1 EPS enhances the anti-tumor efficacies of ICIs by inducing gut-derived CCR6⁺ T cells which modulate the immune microenvironment of tumor tissues. Furthermore, Meiji also showed in a human study with healthy volunteers that consumption of R-1 EPS-containing yogurt increases Th7R cells in the blood. Based on these findings, Saitama Medical University and Meiji jointly initiated a prospective observational study in patients with NSCLC to explore whether similar immune modulation could be observed and how those immune changes may be associated with clinical outcomes.  

In this study 91 NSCLC patients across all treatment settings consumed yogurt containing R–1 EPS daily for four weeks on top of standard therapies, from neoadjuvant treatment to therapies for patients with advanced/recurrent disease. Participant characteristics were generally consistent with those of typical Japanese NSCLC populations. Peripheral blood samples collected before and after treatment were analyzed to track immunological changes in T–cell populations, including Th7R cells. Associations between these immune parameters and clinical outcomes were also analyzed secondarily.

Findings showed this yogurt containing R-1 EPS appears to help maintain Th7R cells in the blood during immunotherapy – a CD4⁺ T cell subset considered to be linked to better, longer-lasting responses to PD-1 inhibitors such as pembrolizumab.

• In patients receiving pembrolizumab, yogurt intake was associated with increased cancer-killing GZMB⁺ CD8⁺ T cells, suggesting enhanced anti-tumor immune activity.
• Among 51 patients treated with combination therapy of ipilimumab and nivolumab, outcomes were favorable with an ORR of 43.3% (vs 35.1% in historical control) and a DCR of 73.3% (vs 64.4%).
• Among the 15 pembrolizumab-treated patients with high PD-L1 expression (TPS ≥50%), outcomes versus historical control were favorable, with an ORR of 58.3% (vs 39.5%) and a DCR of 91.7% (vs 77.6%).
• In the neoadjuvant treatment (including nivolumab) setting, nine patients achieved a 100% response rate (vs 68.0% in historical control), indicating that this simple dietary intervention may meaningfully support the efficacy of modern lung cancer immunotherapy.
• Notably, all three treatment outcomes also exceeded those reported in the Phase III clinical trials of the study's standard therapies that supported their regulatory approval.
• Various types of EPSs produced by lactic acid bacteria have already been granted generally recognized as safe (GRAS) status in the U.S., suggesting EPS' safety and potential suitability for use in medical nutrition applications.

Clinical Outcomes with ICI Therapies

"These findings support our concept that a gut-oriented approach using R–1 EPS improves the distal tumor immune microenvironment and enhances the efficacy of ICIs," said Dr. Kawanabe-Matsuda, Principal Scientist in Wellness Science Labs, Meiji Holdings. "The Meiji Group is advancing plans to bring this adjunctive treatment to patients."

The presented results represent an interim analysis based on data collected during approximately the first year after the start of the study. The study will continue enrolling patients and complete the follow–up period before publishing the final results.

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To support broader applications, Meiji is also developing R-1 EPS in powder form for use across a range of nutritional and healthcare settings. Meiji Holdings is currently pursuing potential business partnerships within the medical food and pharmaceutical industries to bring R-1 EPS powder to local markets worldwide including the U.S. These partnerships will help enable product formulation, clinical research on immuno-nutritional outcomes and supply chain management as well as facilitation of the regulatory process.

Notes
#1 Immune Checkpoint Inhibitors (ICIs): Immune responses that eliminate cancer cells are often suppressed by multiple regulatory "brakes." Immune checkpoint inhibitors, including anti–PD–1 antibodies, work by blocking these inhibitory pathways and reactivating immune responses against tumors. However, because multiple inhibitory mechanisms can be involved, some patients do not respond to these therapies.
#2 Objective Response Rate: The proportion of patients whose tumors either completely disappear or shrink by at least 30%. Disease Control Rate: The proportion of patients whose tumors either completely disappear, shrink by at least 30%, or remain stable (with tumor size changes between a 30% reduction and a 20% increase).

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SOURCE Meiji Holdings Co Ltd