CJRB-101 (live Leuconostoc mesenteroides biotherapeutic) + PD-1 blockade drives 58% ORR in PD-L1-high 1L metastatic NSCLC

CJRB-101 is an oral live biotherapeutic product (novel Leuconostoc mesenteroides strain) designed to remodel the gut microbiome/tumor microenvironment and was combined with pembrolizumab (anti–PD-1) in a first-in-human, multicenter, open-label Phase I dose-escalation/expansion study (NCT05877430) across metastatic NSCLC, HNSCC, and melanoma (n=42; NSCLC 86%; 67% ICI-refractory). No DLTs occurred and there were no grade >3 treatment-related AEs. In ICI-naïve metastatic NSCLC with PD-L1 >50% (n=12), ORR was 58% with DCR 75% and median PFS 9.0 months (95% CI 5.6–NR; median follow-up 15.6 months)—numerically above historical pembrolizumab monotherapy in PD-L1 ≥50% disease (ORR ~39% and mPFS ~7 months in KEYNOTE-024), while ICI-refractory NSCLC (n=22) showed limited activity (ORR 5%, DCR 41%, mPFS 1.8 months; 95% CI 1.6–4.3; median follow-up 8.9 months), which sits in the “hard-to-move” range for post–PD-1 relapse where single-agent salvage chemo historically yields modest responses and short PFS.