In a phase I trial reported in the Journal of Clinical Oncology, D’Souza et al found that the B-cell maturation antigen (BCMA) x CD3 bispecific T-cell redirecting antibody ABBV-383 was active in patients with relapsed or refractory multiple myeloma.

Study Details

In the ongoing trial, 124 patients from sites in the United States and Germany were enrolled between June 2019 and January 2022, including 73 in a dose-escalation phase and 51 in an expansion phase. Patients had received at least three prior lines of therapy (median = 5) including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. ABBV-383 was administered once every 3 weeks at doses of 0.025 to 120 mg in the escalation phase and at 60 mg in the expansion phase.

Responses

Among 122 evaluable patients receiving any dose, objective response was observed in 69 (57%), with very good partial response or better in 52 (43%). Among 49 evaluable patients receiving 60 mg in the expansion cohort, objective response was observed in 29 (59%), with very good partial response or better in 19 (39%). Among 79 evaluable patients who received doses of ≥ 40 mg in the escalation and expansion cohorts, objective response was observed in 54 (68%), with very good partial response or better in 43 (54%), including stringent complete response in 16 (20%) and complete response in 13 (16%). Estimated 6- and 12-month response duration rates were 79.9% and 79.9% in the 60-mg expansion cohort, and 74.8% and 72.2% in the ≥ 40-mg cohort.

Adverse Events

Grade ≥ 3 adverse events, primarily hematologic, occurred in 72% of all patients, 78% of the 60-mg cohort, and 77% of the ≥ 40-mg cohort, the most common being neutropenia (34%, 35%, and 41%). Any-grade cytokine-release syndrome occurred in 57% (grade ≥ 3 in 2%), 71% (grade ≥ 3 in 2%), and 73% (grade ≥ 3 in 4%), respectively. Serious adverse events occurred in 53%, 61%, and 59% of patients; adverse events led to discontinuation of treatment in 10%, 6%, and 7%. Adverse events led to death in seven patients (6%), due to COVID-19 infection in three (at doses of 0.025 mg, 0.2 mg, and 60 mg), sepsis in one (5.4 mg), liver injury in one (50 mg), subdural hematoma in one (90 mg), and plasma cell myeloma in one (60 mg); no deaths were considered related to treatment.

The investigators concluded, “ABBV-383 in patients with relapsed or refractory multiple myeloma was well tolerated with an objective response rate of 68% at doses ≥ 40 mg. This novel therapy’s promising preliminary antitumor activity in heavily pretreated patients warrants further clinical evaluation.”

Shaji Kumar, MD, of the Department of Hematology, Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by AbbVie Inc. For full disclosures of the study authors, visit ascopubs.org.