CAIRE: A basket multicenter open-label phase 2 study evaluating the EZH2 inhibitor tazemetostat in combination with durvalumab in patients with advanced solid tumors.

• DOI: 10.1200/jco.2022.40.16_suppl.tps2703
• Publication Date: 2022-06-06T16:07:22Z
• Authors: Antoine Italiano; Nicolas Isambert; Jean-Philippe Metges; Maud Toulmonde; Sophie Cousin; Simon Pernot; Mariella Spalato; Thomas Grellety; Celine Auzanneau; Barbara Lortal; Michèle Kind; François Le Loarer; Sabrina Sellan-Al...; Carine A. Bellera
• Keywords: Durvalumab

TPS2703 Background: Recent studies have shown that genetic depletion of EZH2 in Tregs (using FoxP3creEZH2fl/fl mice) and pharmacological inhibition elicits phenotypic functional alterations Tregs, leading to an effector-like T cell profile. Further, enhances the cytotoxicity human Teffs vitro proportion tumor-infiltrating cytotoxic cells vivo murine models. It has been immune checkpoint (ICI) increases expression across various tumor types increased inversely correlate with clinical outcome. Upregulation mediated by modulates responses diminishes effectiveness immunotherapy. Consistent this mechanism, pharmacologic increase therapy tumor-bearing mice [16-17]. Our group also reported first data from a participant sarcoma showing strong infiltration after treatment tazemetostat (Italiano et al Lancet Oncol 2018). Altogether, these findings pave way for trials combining ICI specific inhibitor, solid tumors. Methods: CAIRE (NCT04705818) is multi-cohort, four single-arm phase 2, multicenter, open-label study investigating combined durvalumab patients advanced cancers: pancreatic adenocarcinoma (cohort A), microsatellite stable colorectal cancer B), tumors presence tertiary lymphoid structures (assessed centrally) C), soft-tissue sarcomas D). Cohort A will enroll ̃32 cohorts B, C D ̃47 respectively. Eligible must no standard options available or contraindication options, ECOG PS 0–1. Patients prior exposure inhibitor and/or PD1/PDL1 monoclonal antibodies are excluded. Tazemetostat be administered per-os, twice daily (800 mg x 2), continuously. Treatment start on Day 1 (of cycle 1). Durvalumab intravenous infusion (1120 mg) day 1, every 3 weeks. 2. The primary endpoints disease control rate within 24 weeks as per RECIST 1.1 cohort B; objective response C, 6-months non progression D. Secondary include adverse events (AEs)/serious AEs, duration response, progression-free survival. Pharmacodynamic other biomarkers explored. patient received drug July, 30, 2022 site France currently enrolling patients. Clinical trial information: NCT04705818.