EPSTEIN‐BARR VIRUS‐DRIVEN DISEASES: A MULTINATIONAL, MULTICOHORT, OPEN‐LABEL PHASE 2 STUDY TO ASSESS THE EFFICACY AND SAFETY OF TABELECLEUCEL USING AN ADAPTIVE STUDY DESIGN

Introduction: Interleukin-1 receptor-associated kinase 4 (IRAK4) is essential for toll-like receptor (TLR) and interleukin-1 (IL-1R) signaling in immune cells including B lymphocytes. It forms the Myddosome complex with myeloid differentiation primary response 88 (MYD88) adaptor protein, driving maximal activation of Nuclear Factor Kappa (NFkB) causing inflammatory responses tumor promotion. Preclinical studies demonstrated role IRAK4 as a driver secondary, adaptive resistance survival mechanisms that could be delayed or reversed. CA-4948 novel small molecule, oral inhibitor IRAK4. When combined Bruton (BTK) inhibitors, it has shown in-vivo synergy B-cell Non-Hodgkin Lymphoma (NHL) models. was previously reported to well tolerated active monotherapy heavily pretreated relapsed / refractory NHL. Methods: An ongoing trial combination ibrutinib hematologic malignancies (NCT03328078). Rationale: Demonstration between ibrutinib. The study designed follows: Part A: Dose escalation monotherapy, results from phase 1 were presented at American Society Hematology (ASH) 2020. A2 Combination: 3 + design. Primary objectives: Safety/tolerance, maximum dose (MTD), recommended 2 (RP2D). Secondary pharmacokinetics (PK) preliminary efficacy. Exploratory Correlation MYD88-L265P mutation status A basket design expansion cohorts Simon 2-Stage approach, applied each cohort. objective: Efficacy; complete (CR), objective rate (ORR) duration (DOR). Safety tolerance, progression free (PFS) population-PK. biomarkers correlations. Inclusion criteria A2, NHL subtypes (WHO 2016): Follicular lymphoma, marginal zone lymphoma (MZL), mantle cell (MCL), diffused large (DLBCL), chronic lymphocytic leukemia (CLL) and/or (SLL), secondary central nervous system (CNS), Waldenström macroglobulinemia (WM) lymphoplasmacytic (LPL). B: 1-3 include BTK-inhibitor naïve patients similar histologies part cohort includes resistance. Exclusions both Parts Significant acute unresolved toxicity prior therapy; serious co-morbidities. Summary: TLR/myddosome pathway showed preclinical synergistic activity Clinical safety, efficacy selected are being studied. Keywords: Ongoing Trials No conflicts interests pertinent abstract.