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Exploring Dosing Regimens of Sabatolimab Therapy for MDS/AML
Study findings support further exploration of specific dosing regimens of sabatolimab in patients with intermediate- to very high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), according to data presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“Sabatolimab (MBG453) is a high-affinity, humanized, IgG4 (S228P) antibody targeting TIM-3, an inhibitory receptor expressed on multiple immune cells and on leukemic stem/progenitor cells and blasts, but not on normal hematopoietic stem cells,” wrote Andrew H. Wei, MBBS, PhD, The Alfred Hospital and Monash University, Melbourne, Victoria, Australia, and colleagues, who conducted a study examining the use of sabatolimab on patients in the STIMULUS clinical trial.
Specifically, data presented at ASH 2020 focused on the pharmacokinetics (PK) and clinical data supporting the use of sabatolimab doses being evaluated in the STIMULUS program.
Patients with solid tumors were given sabatolimab 80 mg to 1200 mg every 2 weeks (Q2W)/every 4 weeks (Q4W) or sabatolimab 20 mg to 800 mg Q2W/80 mg to 1200 mg Q4W with spartalizumab.
Ultimately, the PK of sabatolimab was found to be similar for patients with solid tumors (n = 252) and HR-MDS/AML (n = 155), and there were no drug-drug interactions seen with any combinations.
Furthermore, among 102 patients with HR-MDS/AML given sabatolimab + HMA and categorized into 4 exposure quartiles based on steady state Cmax and Cavg, a PK exposure-safety analysis showed no relationship between steady state Cmax or Cavg quartiles and incidence of treatment-related AEs. Likewise, no clear relationship observed between steady state Ctrough or Cavg and percent bone marrow blast reduction or clinical benefit (CR/mCR/CRi/PR in an exposure-efficacy analysis (n = 92).
With regard to safety and efficacy, sabatolimab + HMA was safe and well-tolerated with a low rate of study discontinuation because of adverse events (AEs; 3.4%).
“Rates of most common grade ≥3 treatment-emergent AEs and rates of grade ≥3 possible immune-mediated AEs related to study treatment did not appear to be dose dependent,” the investigators reported.
Among evaluable patients with HR-MDS (n = 35) given sabatolimab 240 mg Q2W, 400 mg Q2W, and 800 mg Q4W, CR/mCR/PR rates were 50.0%, 33.3%, and 54.5%, respectively. Among evaluable patients with AML (n = 60), CR/CRi/PR rates were 35.3%, 37.5%, and 31.6%, respectively. No notable differences were observed in the responses across the 3 doses.
“Sabatolimab 400 mg Q2W was predicted to have the highest steady state Ctrough and TIM-3 occupancy rate when combined with HMA, and 800 mg was predicted to be an equivalent Q4W dosing regimen,” Dr Wei et al reported.
“These results support clinical development of the sabatolimab 400 mg Q2W and 800 mg Q4W dosing regimens,” they concluded.—Hina M. Porcelli
Wei AH, Esteve J, Porkka K, et al. Sabatolimab (MBG453) Dose Selection and Dose-Response Analysis in Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML): Population Pharmacokinetics (PK) Modeling and Evaluation of Clinical Efficacy/Safety By Dose. Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 2192.
