Abstract
The T cell–engaging bispecific antibody ABBV-383 was well tolerated in relapsed/refractory multiple myeloma (RRMM).
Major Finding: The T cell–engaging bispecific antibody ABBV-383 was well tolerated in relapsed/refractory multiple myeloma (RRMM).
Concept: Preliminary assessments indicated antitumor efficacy of ABBV-383 in this patient population.
Impact: The promising activity of ABBV-383 in RRMM suggests further clinical evaluation of its use in this disease.
Although treatment options for multiple myeloma (MM) have improved, most patients will eventually relapse, with these individuals demonstrating a poor prognosis. B-cell maturation antigen (BCMA) has evolved as a promising therapeutic target in MM due to its robust expression, and one BCMA-targeted therapy is ABBV-383. ABBV-383 is a next-generation, fully human, IgG4 T cell–engaging bispecific monoclonal antibody that incorporates a low-activating CD3, and its use in preclinical studies indicated antitumor activity and tolerability in vivo. Therefore, D'Souza and colleagues conducted a first-in-human phase I clinical trial of ABBV-383 in 124 patients with relapsed/refractory MM (RRMM) to assess safety and clinical activity. The primary endpoint of this study was safety, tolerability, and clinical pharmacology as well as the maximum tolerated dose or recommended phase II dose. The secondary endpoint was clinical activity. Safety assessments indicated the most common hematologic treatment-emergent adverse events (TEAE) were neutropenia and anemia, while the most common nonhematologic TEAEs were cytokine release syndrome and fatigue, with serious TEAEs in the overall population occurring in 66 patients (53%). The maximum tolerated dose was not reached during the dose-escalation phase, with dose expansion being initiated with a dose of 60 mg. Evaluation of efficacy showed that the overall response rate and very good partial response were 57% and 43%, respectively, across all evaluable groups, with 11 patients having a complete response or stringent complete response, and eight of these 11 (73%) were negative for minimal residual disease. Median duration of response of patients who received a partial response or better (69 patients) had not yet been reached at the time of data cutoff, with the median progression-free survival being 10.4 months for the overall patient population. Overall, this trial indicates that ABBV-383 is well tolerated at all administered doses and shows promising efficacy of this treatment in patients with RRMM, suggesting that further clinical investigation of this molecule is warranted.
Note:Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.
RSS Feeds