CBM588 (Clostridium butyricum live biotherapeutic) + ICB combos drives big PFS/ORR gains in dysbiotic 1L mRCC

CBM588 is an oral Clostridium butyricum–based live biotherapeutic intended to modulate the gut microbiome; here it was added to standard first-line immune checkpoint–based regimens (nivolumab/ipilimumab or nivolumab/cabozantinib) in a pooled analysis of two randomized Phase I mRCC trials (NCT03829111; NCT05122546). In treatment-naïve mRCC (n=59; SOC+CBM588 n=39 vs SOC n=20), SOC+CBM588 improved ORR to 66.7% vs 20.0% (p=0.001) and median PFS to 32.1 vs 3.7 months (HR 0.36, p=0.001)—numerically far above typical first-line benchmarks for approved ICB-based doublets like nivolumab/ipilimumab (ORR ~41.6%, mPFS ~11.6 months in intermediate/poor-risk) and nivolumab/cabozantinib (ORR ~56%, mPFS ~16.6 months vs sunitinib) in Phase III programs, though cross-trial comparisons are especially fragile given the very small SOC control here. Using baseline TOPOSCORE (metagenomic dysbiosis index), benefit appeared concentrated in dysbiotic SIG1+ patients (mPFS 24.9 vs 2.8 months; HR 0.19, p<0.001) with less separation in non-dysbiotic SIG2+ (32.0 vs 10.9 months; HR 0.49, p=0.149); predictive signal also looked backbone-dependent (S score associated with response in the nivo/ipi cohort but not nivo/cabo). Safety outcomes were not reported in this abstract.