In a phase I study reported in the Journal of Clinical Oncology, Max S. Topp, MD, and colleagues found the maximum tolerated dose of the investigational anti–B cell maturation antigen (BCMA) bispecific T-cell engager (BiTE) molecule AMG 420 elicited a high response rate in patients with relapsed or refractory multiple myeloma.
Max S. Topp, MD
Study Details
In the multicenter study, 42 patients with disease progression after two or more lines of prior therapy and no extramedullary disease received AMG 420 at 0.2 to 800 µg/d for up to ten 6-week cycles consisting of 4 weeks of continuous infusion followed by 2 weeks off treatment. Minimal residual disease (MRD) response was defined as < 1 tumor cell/104 bone marrow cells on flow cytometry.
Treatment Outcomes
Among all patients, the median number of cycles was one; among those with response, the median number of cycles was seven. The maximum tolerated dose was 400 µg/d, with one case each of grade 3 cytokine-release syndrome and grade 3 polyneuropathy being observed at the dose of 800 µg/d.
KEY POINTS
- The maximum tolerated dose was 400 µg/d.
- At this dose, response was observed in 7 of 10 patients.
Among all 42 patients, response was observed in 13 (31%). Response was observed in 7 (70%) of 10 at the maximum tolerated dose of 400 µg/day, with responses consisting of MRD-negative response in 5, partial response in 1, and very good partial response in 1. All seven patients with a reported response in this dose group responded during the first cycle. Additional responses were observed at the 6.5-, 50-, 100-, and 800-µg dose levels. Among all 13 responders, responses had a median duration of at least 8.4 months (range = 2.5 to > 15.5 months) and lasted for > 1 year in 3 patients; responses were ongoing at last observation in 7 responders.
Serious adverse events were observed in 20 patients (48%), including infections in 14 and polyneuropathy in 2. Adverse events led to treatment discontinuation in seven patients (17%), with causes consisting of line/port infections in three, peripheral polyneuropathy in two, biliary obstruction in one, and cytokine release syndrome in one. No grade ≥ 3 central nervous system toxicities were observed. Adverse events led to death in two patients; one died from acute respiratory distress from concurrent influenza and aspergillosis, and one died from fulminant hepatitis related to adenovirus infection. Neither death was considered related to treatment. No anti–AMG 420 antibodies were detected.
The investigators concluded, “In this study of AMG 420 in patients with relapsed/refractory multiple myeloma, the response rate was 70%, including 50% MRD-negative complete responses at 400 µg/d, the maximum tolerated dose for this study.”
Dr. Topp, of the Medizinische Klinik II, Universitätsklinikum, Würzburg, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was conducted by Boehringer Ingelheim. The analyses were funded by Amgen. For full disclosures of the study authors, visit ascopubs.org.
