In updated results from the first-in-human study of the bispecific T-cell engager (BITE) AMG 420, the agent continued to demonstrate clinical activity in patients with heavily pretreated, relapsed/refractory multiple myeloma (MM). However, there are concerns about infection and peripheral neuropathy (PN) risks.
Max S. Topp, MD, from the University Hospital of Wuerzburg in Germany, shared the findings at the 2019 ASCO Annual Meeting, which update phase I data that were presented at the 2018 American Society of Hematology Annual Meeting.
As of the data cutoff (February 7, 2019), 42 patients (median age = 65 years; range = 39-79 years) were treated with AMG 420, at doses ranging from 0.2 to 800 µg per day. All participants had MM that progressed after at least two lines of therapy (including a proteasome inhibitor and an immunomodulatory drug), and the median prior lines of therapy was 4 (range = 2-13).
The median time from diagnosis to enrollment was 5.2 years (range = 1.3-20 years), and most patients (55%) had standard risk cytogenetics.
Participants received a maximum of five six-week cycles of AMG 420; treatment continued until disease progression, toxicity, or consent withdrawal. If patients were benefiting from AMG 420 treatment, they could receive five more cycles.
The 800 µg per day dose was determined to not be tolerable, as two of three patients experienced a dose-limiting toxicity (grade 3 cytokine release syndrome and grade 3 PN). These adverse events (AEs) eventually resolved after hospitalization. The maximum tolerated dose (MTD), therefore, was 400 µg per day.
Two patients completed all 10 planned cycles of treatment and are still receiving treatment. More than half of participants (n=25; 60%) discontinued treatment because of progressive disease, while seven discontinued due to AEs (including the 3 dose-limiting toxicities) and one withdrew consent.
Four patients (10%) died during study follow-up; two deaths were attributed to AEs (acute respiratory distress from flu/aspergillosis and fulminant hepatitis related to adenovirus infection) and two to progressive disease. However, Dr. Topp reported that none of the deaths were considered treatment related.
Nineteen patients (45%) experienced serious AEs, 16 of whom required hospitalization. The most commonly reported serious AEs included infections (n=13; 31%) and PN (n=2; 5%). During his presentation, Dr. Topp acknowledged that the frequency of infections is concerning, advising that “careful evaluation of infections should be conducted in future clinical trials to enable development of optimal management guidelines.”
As of April 2019, 13 patients (31%) responded to treatment, including:
- 6 measurable residual disease (MRD)–negative complete responses (CRs)
- 3 CRs
- 2 very good partial responses (VGPRs)
- 2 PRs
Among the 10 patients receiving the MTD of 400 µg per day, five patients achieved an MRD-negative CR and one patient each achieved a PR and VGPR, for an overall response rate of 70%. All of these responses occurred during the first treatment cycle, Dr. Topp added.
Though longer-term follow-up is needed to confirm this observed activity, the researchers noted that responses at this dose level lasted for a median of 9 months (range = 5.8-13.6 months).
These data are limited by the small patient cohort, but the investigators concluded that further investigation of AMG 420 is warranted.
The authors report relationships with Amgen and Boehringer-Ingelheim, which sponsored the study.
Topp MS, Duell J, Zugmaier G, et al. Evaluation of AMG 420, an anti-BCMA bispecific T-cell engager (BiTE) immunotherapy, in R/R multiple myeloma (MM) patients: Updated results of a first-in-human (FIH) phase I dose escalation study. Abstract #8007. Presented at the 2019 ASCO Annual Meeting, June 2, 2019; Chicago, IL.