Abstract CT125: A phase 1/2 randomized study of IGM-2323 in relapsed/refractory non-Hodgkin lymphomas
Authors: Nastoupil Loretta , Budde Elizabeth , Kim Won Seog , Gopal Ajay , Cheah Chan , Flinn Ian , Gregory Gareth , Matasar Matthew , Diefenbach Catherine , Ku Matthew , Yoon Sung-Soo , Qazi Ibrahim , Wei Rachel , Leabman Maya , Hernandez Genevive , Sison Iris , Keyt Bruce , Manley Thomas , Armand Phillipe 
Published: June 2022

Abstract
Background: Recent advances in the treatment of non-Hodgkin lymphoma (NHL) have transformed the landscape and provided significant benefits to patients. Novel agents that target CD19 and CD20 on B cells, such as bispecific T-cell engagers and chimeric antigen receptor (CAR) T cell therapy, have demonstrated benefit for patients in the relapsed and refractory setting. However, these agents can often be associated with significant toxicity and there is a need for new therapies that can provide clinical benefit while providing an improved safety profile.IGM-2323 is a novel CD20 x CD3 bispecific antibody utilizing an IgM backbone. This allows targeting of up to 10 CD20 binding sites for every CD3 site. In preclinical models, IGM-2323 demonstrated excellent antitumor activity with controlled T-cell activation. IGM-2323 is able to stimulate T cells at a more physiologic level than IgG-based antibodies, which may reduce adverse events typically associated with T-cell engagers and CAR-T, such as CRS and neurotoxicity.
Methods: This study is a phase 1/2, multicenter, single-arm clinical trial of IGM-2323 monotherapy for patients with relapsed/refractory NHL. The Phase 1 component consists of a dose escalation and limited dose expansion evaluating multiple titration dose levels. As part of the titration dosing regimen, subjects receive weekly dosing on Day 1, 8, and 15 of each 21- day cycle. Dosing begins at 15 mg and is increased weekly for 3-4 weeks to reach the plateau dose. Patients then stay at the plateau dose until disease progression or unacceptable toxicity. Patients who achieve a response by Week 12 may switch to a less frequent dosing interval of every 3 weeks. The Phase 2 component will randomize patients at two different dose levels (100 mg and 300 mg plateau dose) in two separate indications (R/R DLBCL and R/R FL). Primary endpoints include frequency and severity of adverse events and objective response rate (ORR) based on Lugano criteria. Correlative biomarker studies will evaluate the correlation of clinical benefit with blood and tissue biomarkers. In Phase 2, there will be a formal analysis after 30 subjects are evaluable at each dose level and the best dose for each indication will be selected for further evaluation. The study is currently open with 47 patients enrolled at time of submission. Phase 2 is expected to begin enrollment in the first quarter of 2022. Clinical trial information: NCT04082936.
Citation Format: Loretta Nastoupil, Elizabeth Budde, Won Seog Kim, Ajay Gopal, Chan Cheah, Ian Flinn, Gareth Gregory, Matthew Matasar, Catherine Diefenbach, Matthew Ku, Sung-Soo Yoon, Ibrahim Qazi, Rachel Wei, Maya Leabman, Genevive Hernandez, Iris Sison, Bruce Keyt, Thomas Manley, Phillipe Armand. A phase 1/2 randomized study of IGM-2323 in relapsed/refractory non-Hodgkin lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT125.