|The following article features coverage from the American Society of Hematology (ASH) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Results of a first-in-human phase 1 dose escalation study of AMG 420 in patients with relapsed and/or refractory multiple myeloma (ClinicalTrials.gov Identifier: NCT02514239) were presented by Max Topp, MD, of the University Hospital of Würzburg in Germany, at the 2018 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.1
Patients received 6-week cycles of AMG 420, where 1 cycle was defined as 4 weeks of continuous IV infusion via a pump with 2 week break. Initially single patient cohorts received 0.2 µg/day to 1.6 µg/day, eventually 3- to 6-patient cohorts received 3.2 µg/day to 800 µg/day.
The study enrolled patients with relapsed or refractory multiple myeloma whose disease had progressed after 2 or more prior treatments. Patients with plasma cell leukemia, extramedullary relapse, known central nervous system involvement, or prior allogeneic stem cell transplant were excluded from the trial.
In total, 42 patients received AMG 420 at a dose of 0.2 µg/d to 800 µg/d. Twenty-one patients discontinued treatment due to disease progression, 7 patients discontinued due to adverse events (3 of which were dose-limiting toxicities), 4 patients died (2 due to disease progression and 2 as a result of infections), 2 patients discontinued treatment after the completion of 10 cycles, and 1 patient withdrew consent. As of May 2018, 7 patients were receiving ongoing treatment.
Patients were 64% male (27 patients), mean age was 62.6 years. The median duration of disease on the study was 5.2 years (range, 1.3 to 20) and the median number of prior treatments was 4 (range, 2 to 10).
The researchers found that the dose of 800 µg/day was not tolerable after 2 of 3 patients experienced a dose-limiting toxicity, which included grade 3 cytokine release syndrome (CRS) within 1 day of initiating treatment and grade 3 peripheral polyneuropathy. Of the doses that were tested in this trial, the researchers found that 400 µg/day was the maximum tolerated dose.
Complete response was observed in 7 patients at doses of 6.5 µg/d (1 patient), 100 µg/d (1 patient), 200 µg/d (1 patient), and 400 µg/day (4 patients). There were also 4 partial remissions at datacut. Response duration was for up to 8 cycles.
Patients experienced serious adverse events including cytokine release syndrome (16 patients), infections (12 patients), peripheral polyneuropathy (2 patients), and edema (1 patient). Of the patients who experienced serious adverse events, 17 patients were hospitalized and 4 had prolonged hospitalization. No grade 3 or 4 central nervous system toxicities were observed. Serious infections occurred in 12 patients, including pneumonia, central line infections, port infections, adenovirus, aspergillus/influenza, bronchio-pulmonary infection, and fever of unknown origin. Two deaths occurred as a result of infection but neither were considered related to AMG 420.
“AMG 420, a short half-life BiTE® targeting BCMA, demonstrated clinical activity in patients with heavily pretreated multiple myeloma,” Dr Topp concluded. “Careful evaluation of infections should be conducted in future clinical trials to enable development of optimal management guidelines.”
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2018 meeting by visiting the conference page.
- Topp MS, Duell J, Zugmaier G, et al. Treatment with AMG 420, an anti-B-cell maturation antigen (BCMA) bispecific T-cell engager (BiTEÂ®) antibody construct, induces minimal residual disease (MRD) negative complete responses in relapsed and/or refractory (R/R) multiple myeloma (MM) patients: results of a first-in-human (FIH) phase I dose escalation study. Oral presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 1010.