Monotherapy with AVID200, a potent and selective transforming growth factor β (TGFβ) 1/3 trap, may improve symptoms, spleen size, and platelet counts in patients with myelofibrosis (MF), according to the results of a phase 1b dose-escalation clinical trial published in Clinical Cancer Research.

No dose-limiting adverse events were observed during the clinical trial at 3 different dose levels. The only grade 3/4 hematologic adverse events observed during the trial were anemia in 6 patients (28.6%) and thrombocytopenia in 4 patients (19.0%). No fatal events or cardiac adverse events were recorded during the trial.

Read more about MF experimental therapies

Across all treatment cycles in the study, there was a 40% reduction in total symptom score (range, -100% to 185.7%) and 9 patients (47.4%) achieved greater than 50% reduction in TSS across the study.

Clinical improvement (CI), as defined by the revised International Working Group / European Leukemia Net (IWG/ELN) criteria, was achieved by 2 patients at 7 weeks of the study. At 12 weeks of treatment, 3 out of the 4 patients achieved CI.

While the median change in palpable spleen size was 0.0% during the study (range, -70% to 140%), 2 of the 15 patients with splenomegaly at baseline attained a 50% reduction in spleen length during the trial. A 25% reduction in spleen length was achieved by 5 (33.3%) of patients at any point during the trial.

Platelet counts increased in 17 out of 21 (81%) patients during the study and even reached normal levels in 3 patients. The median baseline platelet counts were 114 x109/L which increased to 215 x 109/L after 6 cycles in 8 patients. This data is in contrast to the currently approved treatments for MF which tend to cause treatment-related thrombocytopenia.

TGFβ1 were elevated at baseline in the trial participants but significantly decreased after treatment (P <.05). The number of CD42b+ megakaryocyte (MK) were elevated in all patients at baseline and these cells expressed barely detected levels of GATA1. In patients who responded to treatment with increased platelet levels, the levels of GATA1 expression increased while the expression levels decreased in the non-responding patients.

“We propose that future trials of AVID200 should include patients at an earlier stage of their disease in order to determine if AVID200 is capable of preventing the progression of bone marrow fibrosis,” the authors suggested.

“We also suggest that administration of AVID200 be combined with other agents that target non-canonical TGF-β pathways or other MF dysregulated intracellular signaling pathways that are currently not employed due to pre-existing MF associated thrombocytopenia,” the authors wrote.


Mascarenhas J, Migliaccio AR, Kosiorek H, et al. A phase 1b trial of AVID200, a TGFβ 1/3 trap, in patients with myelofibrosis. Clin Cancer Res. Published online July 13, 20236. doi:10.1158/1078-0432.CCR-23-0276