Abstract 1367: Relationship between exposure and safety/efficacy of loncastuximab tesirine (Lonca) in B-cell non-Hodgkin lymphoma (B-NHL)

Lonca (ADCT-402) is an antibody (Ab) drug conjugate comprising a humanized anti-CD19 monoclonal Ab, conjugated with a pyrrolobenzodiazepine (PBD) dimer toxin. Lonca showed antitumor activity in a dose-finding Phase 1 study in relapsed/refractory (R/R) B-NHL (NCT02669017), and an open-label Phase 2 (NCT03589469) study in R/R diffuse large B-cell lymphoma (DLBCL), where patients received 150 µg/kg every 3 weeks (Q3W) for two doses, followed by 75 µg/kg Q3W thereafter until disease progression or unacceptable toxicity. Here, we evaluated the efficacy, safety, tolerability, and tolerable doses of Lonca PBD-conjugated Ab (cAb). A pooled Phase 1 and 2 population pharmacokinetics model of total Ab and cAb data was used to generate individual cAb exposure metrics (patients with DLBCL [n=284] for efficacy; all patients [N=328] for safety), including average cAb concentration (Cavg). SAS© v9.4 and R statistical software v4.0.1 were used for the exposure-response analysis. Efficacy endpoints included overall response rate (ORR), overall survival (OS), and duration of response (DoR); selected treatment-emergent adverse events (TEAEs) were used as safety endpoints. Univariate and multivariate logistic regression models were used to analyze ORR and safety endpoints. Time-to-event Kaplan-Meier and a Cox proportional hazards model were used to analyze OS and DoR, as applicable. Significant relationships between exposure and response (ORR and OS) were observed. ORR was 64.8% for patients in the highest quartile (Q4) of Cycle 1 Cavg compared with 23.9% for patients with drug exposure in Q1. The odds of response increased 1.2-fold for each 0.1 µg/kg increase in Cycle 1 Cavg (p Significant positive relationships were found between exposure and increased gamma-glutamyltransferase (GGT), skin and nail disorder, and liver function test abnormalities (but no evidence of hepatotoxicity). The odds of Grade ≥2 GGT occurrence increased with Cavg in Cycle 1 (p=0.000669). Higher Lonca exposure resulted in improved response. As expected, probability of Grade ≥2 TEAEs overall increased with exposure. The dosing regimen using initial dose of 150 µg/kg with dose reduction after two cycles resulted in rapid attainment and maintenance of high steady-state levels, and is anticipated to aid in response durability while minimizing toxicity. Citation Format: Brian Hess, Weiyun Ai, William Townsend, David Ungar, Sam Liao, Lori Liao, Xiaoyan Zhang, Joseph Boni. Relationship between exposure and safety/efficacy of loncastuximab tesirine (Lonca) in B-cell non-Hodgkin lymphoma (B-NHL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1367.