LAUSR

6059 Background: Therapeutic manipulation of the gut microbiome in cancer patients (pts) is an area of active investigation. MET4 (NuBiyota) is an oral alternative to fecal transplant consisting of a mixture of human gut bacteria associated with immunotherapy (IO) response. We previously reported variation in IO-responsive taxa across stages in human papilloma virus related (HPV+) LA-OPSCC pts treated with chemoradiotherapy (CRT) (Oliva et al., ASCO 2020). ROMA-2 is the first interventional study evaluating the safety, feasibility and ecological effect of MET4, in combination with definitive CRT in HPV+ LA-OPSCC (NCT03838601). Methods: This is an investigator-initiated study of pts with HPV+ LA-OPSCC treated with standard of care CRT. MET4 is administered daily until week 4 of CRT or unacceptable toxicity. Stool samples are collected at baseline, week 4, week 8-10, and 2-months post CRT. Bacterial V4 16S rDNA was extracted from stool and sequenced. Microbiome analyses were conducted in R using DADA2, phyloseq and DESeq2. Results: As of February 11 2021, 25 pts have been enrolled. A total of 50 stool samples from the first 14 pts were collected (98% adherence) and analyzed. Baseline cohort characteristics: median age = 62.5 (range, 48-69); Stage I/II/III = 5/1/8; use of antibiotics = 1pt. 3 pts did not complete the 3-week course of MET4 treatment due to non-compliance (n = 1), withdrawal of consent (n = 1) and grade 2 diarrhea (n = 1). Other reported MET4-related adverse events (all grade 1) included bloating (n = 2), flatulence (n = 1) and belching (n = 1). No longitudinal changes in alpha-diversity were seen from baseline through follow up. Administration of MET4 resulted in a transient trend towards increased cumulative MET4 taxa relative abundance (RA) by week 4. Stage III patients demonstrated the lowest MET4 taxa RA at baseline, and the greatest increase in MET4 taxa RA from baseline to week 4. By week 4 the following taxa in all pts were increased compared to baseline: Eubacterium hallii (21.71 Log2Fold change[L2FC], padj < 0.001) and Parabacteroides johnsonii (23.67 L2FC, padj < 0.001). An increase in the following taxa was observed by weeks 8-10 compared to baseline: Akkermansia muciniphilla (3.75 L2FC, padj = 0.027), Bacteroides fragilis (6.73 L2FC, padj = 0.010), Alistipes onderdonkii (3.30 L2FC, padj = 0.049) and Parabacteroides distasonis (24.43 L2FC, padj < 0.001). Conclusions: Manipulation of the gut microbiota in these pts was feasible and safe. MET4-induced ecological changes are heterogenous and vary by taxa. MET4 taxa implicated in IO-response were increased by week 4 and week 8-10. This increase was higher in pts with stage III disease. These data suggest that specific subgroups may benefit from combination IO therapy and may guide pt selection for further interventional clinical trial design. Clinical trial information: NCT03838601.