Introduction

​The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs.

Aims & Methods

​In this single-center phase II pilot study (ClinicalTrials.gov ID: NCT05750030), we plan to include 12 patients with advanced HCC who progressed on atezolizumab/bevacizumab. Patients will receive atezolizumab/bevacizumab every 3 weeks in combination with a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events (TRAEs). The main secondary endpoint is best overall response (BOR) according to RECISTv1.1 and mRECIST. Here, we report results of a preplanned interim analysis.

Results

Of 6 patients included so far, 5 were male, 5 had BCLC stage C, and 5 had Child-Pugh class A. All patients underwent successful FMT without any periinterventional complications. TRAEs related to FMT were all low-grade (grade 1-2) and included bloating (n=2), constipation (n=2), and diarrhea (n=1). TRAEs related to atezolizumab included one grade 2 pruritus, and TRAEs related to bevacizumab included arterial hypertension (one grade 3 and two grade 2) and proteinuria (one grade 3 and one grade 1). All patients had at least one follow-up imaging. Two patients had partial response, 3 patients had stable disease, and 1 patient had progressive disease as BOR according to both RECISTv1.1 and mRECIST, which corresponds to an objective response rate of 33% and a disease control rate of 83%.

Conclusion

Based on acceptable safety and promising efficacy results, the decision to continue recruitment in this trial was made. An update with longer follow-up will be presented at the meeting, including analyses of the gut microbiome.

Disclosure

AF received travel support from Takeda and Amgen, he received speaker honoraria from AbbVie
KP has nothing to disclose.
BS received travel support from AbbVie, AstraZeneca, Gilead and Ipsen, speaker honoraria from Eisai as well as grant support from AstraZeneca and Eisai.
BL received speaker honoraria from Chiesi and Gilead.
LP has nothing to disclose.
AK has nothing to disclose.
KR has nothing to disclose.
KZ has nothing to disclose.
MT received speaker honoraria from Albireo, BMS, Falk Foundation, Gilead, Intercept, Madrigal and MSD; he has advised for Abbvie, Albireo, BiomX, Boehringer Ingelheim, Falk Pharma GmbH, Genfit, Gilead, Hightde, Intercept, Ipsen, Jannsen, MSD, Novartis, Phenex, Pliant, Rectify Regulus, Siemens and Shire. He further received travel grants from Abbvie, Falk, Gilead Intercept and Jannsen and research grants from Albireo, Almylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and Ultragenyx. He is also co-inventor of patents on the medical use of NorUDCA filed by the Medical Universities of Graz and Vienna.
DT served as a speaker and/or consultant and/or advisory board member for Siemens, Roche, Sanova, Bristol-Myers Squibb and received travel support from Bayer and Siemens.
CG nothing to disclose.
MP received speaker honoraria from Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; he is a consultant/advisory board member for AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; he received grants from AstraZeneca, Bayer, BMS, and Roche; he received travel support from Bayer, BMS, Ipsen, and Roche.