P-047: TRIAL IN PROGRESS: AN OPEN-LABEL, MULTICENTER, PHASE 1 STUDY OF IGM-2644 IN PARTICIPANTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (RRMM)

Introduction: IGM-2644 is an engineered high-affinity, high-avidity bispecific anti-CD38 IgM antibody T cell engager (TCE) being developed for the treatment of RRMM. CD38 is a uniformly highly expressed cell surface glycoprotein on neoplastic plasma cells. IGM-2644 is designed to selectively target and kill myeloma cells through both T-cell dependent cellular toxicity (TDCC) and complement dependent cytotoxicity (CDC). In preclinical models, IGM-2644 demonstrates superior CDC and cellular-dependent cytotoxicity compared to daratumumab, especially on low CD38-expressing tumor cells. IGM-2644 may have an improved safety profile compared to bispecific IgGs due to lower cytokine release and reduced immune cell fratricide with comparable anti-tumor activity in ex vivo and in vivo MM models.

Methods: This is a first-in-human, Phase 1, multicenter, open-label study to determine the safety and tolerability of IGM-2644 as a single agent in participants (N=30-60) with RRMM. Expansion cohorts will be enrolled to evaluate preliminary efficacy and further define a recommended Phase 2 dose (RP2D).
A step-up dosing regimen will be used, with successively higher doses of IGM-2644 administered during a priming cycle. The optimal number and magnitude of steps to reach the plateau RP2D will be determined progressively. At the start of dose escalation, the same dose level will be administered on all dosing days during the priming cycle until a Dose 1 is fixed. Doses 2 and 3 will then be increased in parallel until a Dose 2 maximum tolerated dose (MTD) is defined. The Safety Review Committee may recommend fixing Dose 2 at or below the MTD and continuing escalation of the third priming dose.
The highest dose achieved during the priming cycle will represent the plateau dose to be administered once per week in 3-week cycles. Pharmacokinetics, pharmacodynamics, efficacy, and safety data collected throughout the treatment period may be used to support potentially less frequent dosing.
A single participant will initially be enrolled into each dose-escalation cohort. Conversion to a standard 3+3 escalation format will be based on the occurrence of one of specified safety events or the achievement of a predetermined dose level, whichever occurs first. Correlative biomarker studies include assessment of blood and tissue biomarkers for association with clinical benefit.

Results: n/a

Conclusions: IGM-2644 is a novel bispecific IgM T cell engager with both CDC and TDCC mechanisms of cytotoxicity and the potential to be active in daratumumab-resistant tumors. This Phase 1 trial is underway, and results will be presented at a future meeting.