Abstract CT146: AZD0466 in patients with advanced non-Hodgkin lymphoma: Efficacy and safety in an open-label phase 1 trial
Abstract
Background Overexpression of pro-survival proteins Bcl-2 and Bcl-xL have been associated with poor prognosis in patients with non-Hodgkin lymphoma (NHL). AZD0466 is a drug-dendrimer conjugate consisting of the dual Bcl-2/Bcl-xL inhibitor AZD4320 covalently conjugated to a pegylated poly-L-lysine dendrimer, which allows for gradual release by hydrolysis. Preclinically, AZD0466 monotherapy has demonstrated efficacy in xenograft models of diffuse large B-cell lymphoma (DLBCL). Here, we report results from a Phase 1 trial (NCT05205161) of AZD0466 in relapsed/refractory (R/R) advanced B-cell NHL (B-NHL).
Methods Eligible patients were ≥18 years old and had received 2-5 prior lines of therapy. AZD0466 was administered intravenously, with a dose ramp-up on days 1 and 4 of a 28-day cycle, and weekly administration of the target dose from day 8. The primary objective of the dose escalation phase was to assess the safety and tolerability of AZD0466 in patients with R/R B-NHL and to identify the maximum tolerated dose and recommended phase 2 dose. Preliminary efficacy was evaluated using Lugano 2014 criteria. Secondary objective was evaluation of pharmacokinetic (PK) parameters for the study drug.
Results As of November 02, 2023, 7 patients (DLBCL n=5, follicular lymphoma n=1, marginal zone lymphoma (MZL) n=1; median age, 57 [26−79] years) had received AZD0466 at 600 mg (n=3), 1200 mg (n=3), or 2400 mg (n=1). All patients experienced adverse events (AEs). AEs possibly related to…
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