SITC 2021: Engineered Toxin Body Under Study in Resistant Multiple Myeloma
Posted: Monday, November 29, 2021
Monotherapy with the second-generation engineered toxin body TAK-169 seemed to engage CD38 in patients with relapsed or refractory multiple myeloma, according to Shaji Kumar, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues. The interim analysis of this multicenter phase I study, which was presented during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 447) and published in the Journal for ImmunoTherapy of Cancer, also demonstrated a reduction in the number of natural killer cells. The dose-escalation phase of this trial is ongoing.
“Engineered toxin bodies comprise a proprietarily engineered and de-immunized Shiga-like Toxin-I A1 subunit genetically fused to an antibody-like binding domain,” the investigators commented. “[These agents] can force receptor internalization, induce potent cell kill via enzymatic and permanent inactivation of ribosomes and may not be subject to resistance mechanisms of other therapeutics.”
Four heavily pretreated patients were administered TAK-169 at the initial dose level of 50 µg/kg. Treatment was eventually discontinued due to progressive disease (n = 3) and treatment-emergent adverse events (n = 1); these toxicities included asymptomatic grade 2 reversible myocarditis and grade 3 high sensitivity troponin elevation.
Quantifiable drug concentrations were reported in all patients on day 1 of the first cycle; the mean eliminate half-life was 1 hour. The geometric mean of the maximum concentration was 1.73 nM; of note, this is lower than the half maximal effective concentration (5 nM) observed in multiple myeloma cell-killing assays using patient bone marrow aspirates. The number of natural killer cells in peripheral blood was reduced in each of the patients by a maximum of 56%, 85%, 88%, and 92% after the first dose. The patient who experienced a 56% reduction had the lowest natural killer cell count at baseline, along with a low percentage of CD38-positive natural killer cells.
Disclosure: No information regarding conflicts of interest was provided.
