Sabatolimab monotherapy showed promising efficacy in a study of adult patients with acute myeloid leukemia (AML) who are in hematological complete remission (CR) with positive measurable residual disease (MRD+) after allogeneic stem cell transplantation (HSCT).
Led by Robert Zeiser, MD, of the University of Freiburg in Germany, the study reported preliminary data from a safety run-in of the novel immunotherapy sabatolimab at two dose levels: 400 mg or 800 mg intravenous (IV) every four weeks. Twenty-one patients (10 at 400 mg and 11 at 800 mg) were enrolled.
The primary endpoint was incidence of treatment-emergent dose-limiting toxicity (DLT), including acute graft-vs-host disease (GVHD) and chronic GVHD during the first two cycles.
One DLT of grade 3 myocarditis occurred after the first 800 mg sabatolimab infusion. Sixteen patients experienced adverse events (AEs), with eight patients experiencing grade 3 or more AEs such as neutropenia and thrombocytopenia. Two patients at 400 mg experienced serious AEs after the DLT observation period (>3 cycles), and two patients at 800 mg experienced serious AEs during the DLT period.
At the data cutoff, seven patients continued treatment and were in CR (three at 400 mg and four at 800 mg), while fourteen patients discontinued treatment due to disease relapse (seven at 400 mg and seven at 800 mg). Five deaths occurred at 400 mg due to AML.
At 400 mg, two patients received 14 cycles of treatment and one patient received 15 cycles. Seven patients relapsed, including two patients after cycle one, two patients after cycle two, and one patient each after cycles three, four, and seven.
At 800 mg, one patient received five cycles, one patient received six cycles, and two patients received seven cycles. Five patients relapsed, including one patient after cycle one, two patients after cycle two, one patient after cycle three, and one patient after cycle five.
Overall, researchers found that sabatolimab at 400 mg and 800 mg were well tolerated, as cytopenias occurred at low rates, and there were no reported cases of GVHD or any immune-related AEs commonly seen with checkpoint inhibitors.
Zeisler R, Devillier R, Mico M, et al. TIM-3 Inhibitor sabatolimab for patients with acute myeloid leukemia (AML) with measurable residual disease (MRD) detected after allogeneic stem cell transplantation (AlloSCT): Preliminary findings from the phase Ib/II stimulus-AML2 study. Abstract #59. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.