Data from the first-in-human study of AMG 420, an anti-BCMA bispecific T-cell engager (BiTE) immunotherapy, were presented at ASCO 2019.
A first-in-human study of AMG 420, an anti-BCMA bispecific T-cell engager (BiTE) immunotherapy, showed a high rate of response in relapsed or refractory multiple myeloma patients treated at the 400 mcg per day dose, according to data (abstract 8007) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
“This first-in-human study with AMG 420 demonstrated clinical activity in patients that have previously been treated very heavily,” said Max S. Topp, MD, of the University Hospital of Wurzberg in Germany. “From these data, it is definitely clear that we want to extend these trials.”
Enrolled patients were treated with 6-week cycles of AMG 420 for 5 or fewer cycles until disease progression, toxicity, or withdrawal of consent occurred. When the treating physician perceived benefit, 5 more cycles could be given. Dose escalation started in single-patient cohorts from 0.2/mcg per day and increased to 1.6 mcg per day. Cohorts of 3 to 6 patients were tested with doses from 3.2 mcg to 800 mcg per day.
Trial eligibility included progression after 2 or more prior treatments, including a proteasome inhibitor and an immunomodulatory drug. The median age of the 42 patients was 65 years, with a median duration of disease of 5.5 years.
Dose-limiting toxicities occurred at two dosages, according to Topp. At 800 mcg per day, there was 1 patient with cytokine release syndrome and 1 with peripheral polyneuropathy. At the 400 mcg per day level, 1 patient had peripheral polyneuropathy. The 800 mcg per day dose was determined to be not tolerable because 2 of 3 patients had a dose-limiting toxicity. Maximum-tolerated dose was 400 mcg per day.
The overall rate of cytokine release syndrome was 38%, with the vast majority being grade 1 or 2, according to Topp. Of the 19 patients with serious adverse events, 16 were hospitalized and 4 had prolonged hospitalization. Infection was the most common serious adverse event (31%), caused mostly by chest infections (12%) and central line port infections (12%).
Two patients experienced peripheral polyneuropathy, but Topp noted that both cases were improved with IVIg and corticosteroid treatment. One patient had complete resolution in 1 month and the other, with preexisting neuropathy, returned to baseline level in 2 months.
The median number of cycles of treatment given was 2.7. Topp discussed 3 patients who prematurely stopped therapy; all 3 patients, who received either 1 cycle or 4 cycles, continue to be in stable response without receiving further treatment.
At 400 mcg, 5 patients had MRD-negative complete remission, 1 patient had very good partial remission, and 1 had partial remission, for a response rate of 70%. At the most recent examination, responses had lasted for a median of 9 months with 2 patients still on treatment.
In the overall cohort, 13 of 42 patients responded with six complete remissions, three stringent complete remissions, two very good partial remissions, and two partial remissions. Responses lasted for a median of 8.4 months. MRD-negative complete remissions lasted for a median of 9.6 months.
In his discussion of the results, Jesus G. Berdeja, MD, of Tennessee Oncology, called attention to the fact that only 20% of patients on this study had been daratumumab exposed or refractory, which he said “is of interest when you start to compare the different therapies.”
Other positives about this BiTE therapy is that it is “off-the-shelf” treatment, but it is given as a continuous infusion and will require frequent or continuous infusion over several months.
Data on durability of response is awaited, Berdeja said.