In a phase I trial (MajesTEC-1) reported in The Lancet, Saad Z. Usmani, MD, FACP, and colleagues found that the B-cell maturation antigen (BCMA)-CD3 bispecific antibody teclistamab produced a high rate of durable responses at the recommended phase II dose in patients with relapsed or refractory multiple myeloma.

Teclistamab is a bispecific IgG4 antibody that binds BCMA and CD3 to redirect T cells to multiple myeloma cells. According to the investigators, the current study is—to their knowledge—the first report of a T-cell–redirecting bispecific antibody for the treatment of patients with cancer.

Saad Z. Usmani, MD, FACP

Study Details

In the study, 157 patients who had received a median of six prior lines of therapy were enrolled between June 2017 and March 2021 from sites in the United States, Spain, France, the Netherlands, and Sweden. They received teclistamab intravenously (0.3–19.2 μg/kg once every 2 weeks or 19.2–720 μg/kg once per week) or subcutaneously (80–3,000 μg/kg once per week), with step-up dosing for doses ≥ 38.4 μg/kg.

Key Findings

The recommended phase II dose was identified as teclistamab given subcutaneously at 1,500 μg/kg once per week after 60 μg/kg and 300 μg/kg step-up doses. No dose-limiting toxicities were observed at the recommended phase II dose in the dose-finding phase of the trial.

Among 40 patients receiving the recommended phase II dose, the most common adverse events of any grade were cytokine-release syndrome (70%, all grade 1 or 2 ) and neutropenia (65%, grade 3 or 4 in 40%). Grade 3 or 4 adverse events occurred in 80% of patients, with the most common being neutropenia, anemia (28%), and thrombocytopenia (20%). Other common nonhematologic adverse events of any grade were fatigue (38%), nausea (33%), diarrhea (23%), and pyrexia (not associated with cytokine-release syndrome; 13%). Infections occurred in 45% of patients and were grade ≥ 3 in 23%.

Among 40 patients receiving the recommended phase II dose, partial response or better was achieved in 26 (65%), with very good partial response or better in 23 (58%), complete response or better in 16 (40%), and stringent complete response in 7 (18%). Median times to response were 1.0 months to first confirmed response, 1.1 months to very good partial response or better, and 3.0 months to complete response or better. Median duration of response was not reached (95% CI = 7.2 months–not reached), with 22 (85%) of 26 responders remaining alive and continuing treatment after a median follow-up of 7.1 months (interquartile range [IQR] = 5.1­­–9.1 months).

The investigators concluded, “Teclistamab is a novel treatment approach for relapsed or refractory multiple myeloma. At the recommended phase II dose, teclistamab showed promising efficacy, with durable responses that deepened over time, and was well tolerated, supporting further clinical development.”

Saad Z. Usmani, MD, of Levine Cancer Institute/Atrium Health, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit thelancet.com.