607 CONSORTIUM-IO: a phase 1 study evaluating a combination of an 11-strain bacterial consortium (VE800) and nivolumab in treatment of select refractory or metastatic cancers

• DOI: 10.1136/jitc-2024-sitc2024.0607
• Publication Date: 2024-11-05T14:58:58Z
• Authors: Carolina Lyon De Ana; Amanda Prince; Erica Darrah; Scott Buresh; Rajita Menon; Jason Norman; Rose Szabady; Dmitri Bobilev; Judy S Wang; Jeremiah Faith; Jeffrey Silber; Bernat Olle; Diwakar Davar
• Keywords: Refractory (planetary science); Strain (injury)

<h3>Background</h3> The gut microbiome can predict response and adverse events (AEs) in patients with solid tumors receiving anti-programmed cell death protein-1 (anti-PD1) agents like Nivolumab.^{1 2} Microbiome modulation fecal microbiota transplantation (FMT) demonstrates the potential of reversing PD-1 resistance melanoma.^3–5 However, FMTs are variable composition, difficult to scale, risk transfer emerging pathogens. VE800 is an 11-strain bacterial consortium made from clonal banks derived healthy donors. produced anti-tumor efficacy combination Nivolumab mouse models.⁶ CONSORTIUM-IO was a first-in-human, open-label phase 1 study that evaluated safety VE800+nivolumab anti-PD1-refractory melanoma, gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, microsatellite-stable colorectal cancer (CRC-MSS). primary endpoints were efficacy, determined by incidence AEs objective rate (ORR). <h3>Methods</h3> After 5 days vancomycin (125mg po QID), subjects received (5 capsules [5x10⁸ colony-forming units per capsule] QD x7 days, then capsule until end trial) (480mg IV Q4W). Subjects followed for safety, strain colonization, immune biomarkers. Stool peripheral blood mononuclear cells (PBMCs) collected baseline Week 12. metagenomic sequencing performed detect strains all subjects, analysis only melanoma cohort (figure 1a). <h3>Results</h3> 54 enrolled: CRC-MSS (n=14), G/GEJ (n=20) adenocarcinoma (n=20). No dose-limiting toxicities (DLTs) observed, most common experienced consistent those seen monotherapy.⁷ ORR disease control (DCR) low: 1.9% 27.8%, respectively. DCR were: (0% 21.4%), (5% 15.0%) 45.0%) 1b). colonized robustly cohorts up week 4 1c). In cohort, better engraftment (N&gt;5 colonized) associated longer progression-free survival (PFS) (Cox model, p=0.07, Hazard ratio Low Engraftment (LE)/High (HE)= 2.53) 1d). increased frequencies IFN-γ TNF-α producing CD8 T (p&lt;0.05) HE. <h3>Conclusions</h3> well-tolerated advanced CRC-MSS, melanoma. Although low cohorts, HE improved PFS 1d) inflammatory cells. Improved circulating suggest benefit VE800+Nivolumab <h3>Acknowledgements</h3> We acknowledge contributions investigators site staff, as well who enrolled. <h3>Trial Registration</h3> Trial Registration: NCT04208958. <h3>References</h3> McCulloch JA, Davar D, Rodrigues RR, <i>et al</i>. Intestinal signatures clinical immune-related treated anti-PD-1. <i>Nat Med</i> 2022 Mar;<b>28</b>(3):545–556. Chaput N, Lepage P, Coutzac C,<i> et Baseline predicts colitis metastatic ipilimumab.<i> Ann Oncol</i> 2017 Jun 1;<b>28</b>(6):1368–1379. Dzutsev AK, JA,<i> Fecal transplant overcomes anti-PD-1 therapy patients.<i> Science</i> 2021 Feb 5;<b>371</b>(6529):595–602. Baruch EN, Youngster I, Ben-Betzalel G, promotes immunotherapy-refractory patients. <i>Science</i> 5;<b>371</b>(6529):602–609. Routy B, Lenehan JG, Miller WH,<i> plus immunotherapy melanoma: I trial. 2023 Aug;<b>29</b>(8):2121–2132. doi: 10.1038/s41591-023-02453-x. <i>Epub</i> Jul 6. Erratum in: 2024 Feb;<b>30</b>(2):604. 10.1038/s41591-023-02650-8. PMID: 37414899. Tanoue T, Morita S, Plichta DR, A defined commensal elicits anti-cancer immunity. <i>Nature</i> 2019 Jan;<b>565</b>(7741):600–605. Martins F, Sofiya L, Sykiotis GP,<i> Adverse effects immune-checkpoint inhibitors: epidemiology, management surveillance. Rev Clin Sep;<b>16</b>(9):563–580. <h3>Ethics Approval</h3> protocol informed consent documents approved respective sites' Institutional Review Boards. University Utah IRB, IRB_00128490 Pittsburg Medical Center MOD00655221, Pro00039903 Advarra IRB Intelligence Platform, MOD0146106, 00000971 WCG Board, Study Numbers: 1282434, 1273387, 1275793, 1283587 New York School Medicine Number i19-00845 Rhode Island Hospital &amp; Miriam 204120 California Los Angeles, IRB#20--000133-AM00006 Cedars Sinai Samuel Oschin Comprehensive Cancer Institute, CR2019-1002-0 Chicago Center, IRB19-1676 Sutter Health 1549521-7 Weill Cornell Medicine, 20-02021418. <h3>Consent</h3>