According to the results of a first-in-human, phase 1b study, the T cell-engaging bispecific antibody APVO436 exhibited a favorable safety profile, with acceptable tolerability and manageable drug-related adverse events (AEs), in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The report was published in Cancers.
In this open-label, dose-escalation study (ClinicalTrials.gov Identifier: NCT03647800), the investigators aimed to determine the safety and tolerability of APVO436 in patients with R/R AML or MDS and to identify a recommended phase 2 dose (RP2D) level. Adult patients with histologically confirmed AML or MDS who had failed 1 to 8 prior lines of therapy were enrolled in the study at 10 sites between May 15, 2018 and June 4, 2021. The data cutoff date was July 22, 2021.
To determine the RP2D, 46 R/R AML/MDS patients received intravenous infusion of APVO436 weekly at 10 different dose levels (3 to 6 patients per level) ranging from 0.3 mcg to 60 mcg, for up to 6 28-day cycles or until disease progression, unacceptable toxicities, or withdrawal of consent. At the discretion of the treating physician, patients could receive up to 36 cycles of AVPO436 if a treatment benefit was observed.
The patients had a median age of 69 years (range, 18-82 years) and had failed an average of 3.2 lines of therapy. Most patients (84.8%) had R/R AML. Patients received a median of 7 doses of APVO436 (range, 1-43 doses). The median overall survival was 178 days; most patients (71.7%) died or were transferred to hospice care.
APVO436 was well tolerated. The maximum tolerated dose was not reached at a weekly flat dose of 60 mcg, with no dose-limiting toxicity or grade 3-4 AEs. Drug-related AEs were manageable. The most common of which were infusion-related reactions (28.3%) and cytokine release syndrome (21.7%). The single dose RP2D level was identified as the 18 mcg flat dose (or 0.2 mcg/kg).
Preliminary efficacy signals were reported for both patients with AML and MDS. Among 8 patients with R/R AML, the investigators observed prolonged stable disease, partial remissions, and complete remissions as best overall responses to APVO436, including at the RP2D level. Among 6 evaluable MDS patients, 3 had marrow CRs.
“The safety, feasibility, and preliminary clinical activity of APVO436 in R/R AML and MDS deserves further clinical investigation, and combination therapy cohorts as well as consolidation/MRD therapy cohorts are now underway for AML patients in an expansion study,” the authors wrote.
Disclosure: This research was supported by Aptevo Therapeutics. Please see the original reference for a full list of disclosures.
Uckun FM, Lin TL, Mims AS, et al. A clinical phase 1B study of the CD3xCD123 bispecific antibody APVO436 in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome. Cancers (Basel). 2021;13(16):4113. doi:10.3390/cancers13164113