1699P - Impact of Latino ethnicity on the gut microbiome and response to immune checkpoint inhibition (ICI) with CBM588 in patients (pts) with metastatic renal cell cancer (mRCC)

Background

The composition of the gut microbiome can impact outcomes with ICIs (Routy et al Science 2018) and Latinos with mRCC have a different gut microbiome composition than their non-Latino counterparts (Barragan-Carrillo et al ASCO 2024). Two trials provided evidence that CBM588, a live biotherapeutic, improved outcomes in pts with mRCC on ICI (Dizman et al Nat Med 2022; Ebrahimi et al ASCO 2023). Herein we analyze the impact of CBM588 on the gut microbiome and clinical outcome between Latino and non-Latino pts with mRCC.

Methods

We analyzed stool samples from two phase I trials that enrolled pts with mRCC treated with frontline nivolumab/ipilimumab or nivolumab/cabozantinib +/- CBM588. Pts were dichotomized into Latino and non-Latino groups. Stool specimens were collected at week 12 of treatment. Whole metagenomic sequencing was performed on stool specimens. ANCOM-BC analysis was used to identify differences in the relative abundance of bacterial species (spp) between groups. α-diversity was evaluated using the Shannon diversity index, and β-diversity was assessed using the Bray-Curtis and Jaccard dissimilarity measures.

Results

Among 59 pts with mRCC, 27 were Latino and 32 non-Latino. Median age was 60, most had clear cell histology (88%) and intermediate/poor risk disease (79%). Randomization to CBM588 was balanced between Latino and non-Latino patients (59% v 71%, respectively; P=0.30). Disease control rate (DCR) in Latino pts treated with CBM588 was higher than in non-Latino pts (100% vs. 70%, P=0.01). In the CBM588 group, enrichment of 6 bacterial spp and depletion in 8 spp was observed in Latino pts. The gut microbiome of Latino pts was enriched by spp associated with ICI benefit (p≤.05), including Roseburia faecis (LFC 2.4) and Roseburia spp AF02 12 (LFC 1.93). We saw no difference in α and β diversity between Latinos and non-Latinos, with and without CBM588.

Conclusions

Latino pts who received ICI with CBM588 had a higher DCR as compared to non-Latino pts. Additionally, they exhibited increased bacterial spp linked to favorable outcomes with ICIs. Our findings suggest that trials aimed at modulating the microbiome could have unique value in minority populations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

City of Hope Comprehensive Cancer Center.

Funding

Has not received any funding.

Disclosure

A. Chehrazi-Raffle: Financial Interests, Personal, Advisory Board: Exelixis, Inc, Aveo Inc., Pfizer Inc.; Financial Interests, Personal, Invited Speaker: Exelixis, Inc, OncLive/MJH Life Sciences, ASCO Direct. S.K. Pal: Financial Interests, Institutional, Local PI: Eisai, Genentech, Roche, Exelixis, Pfizer, CRISPR Therapeutics, Allogene Therapeutics, Xencor, Novartis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Leadership Role: SWOG; Other, Travel reimbursement: CRISPR, Roche. All other authors have declared no conflicts of interest.