A new phase 1 clinical trial evaluating the safety, tolerability, and dose limiting toxicity of INCA033989 as a monotherapy or in combination with ruxolitinib in patients with myeloproliferative neoplasms including myelofibrosis (MF) is now recruiting participants. 

The open-label, multicenter trial sponsored by Incyte Corporation will also determine the maximum tolerated dose and/or recommended dose(s) of INCA033989 alone or together with ruxolitinib. 

Read more about the treatment of MF

Participants will first be given INCA033989 at a protocol defined starting regimen in 28-day cycles on its own to identify the maximum tolerated dose and/or recommended dose for expansion. 

Patients with MF with a suboptimal response to treatment will allow for the evaluation of INCA033989 as an add-on therapy in combination with ruxolitinib.

Then INCA033989 will be given as monotherapy or together with ruxolitinib (depending on the response to treatment) at the recommended dose for expansion identified during the first part of the study. 

Finally, INCA033989 will be given to treatment-naive participants at the dose that led to overall positive benefit/risk as monotherapy or together with ruxolitinib. If a suboptimal response to INCA033989 monotherapy is observed after 12 weeks, participants enrolled in this arm will have the choice to cross over to the combination therapy arm of the study.

The primary outcome measures are the number of participants with dose limiting toxicities, treatment-emergent adverse events, and treatment-emergent adverse events leading to dose modification or discontinuation.

Secondary outcome measures include percentage of participants achieving spleen volume reduction of at least 35%, anemia response, and pharmacokinetics parameters.

The trial aims to recruit 225 patients with MF or essential thrombocythemia at 23 locations across the world.

It opened on June 30, 2023 and is expected to be comoleted on February 29, 2028.

MF is a rare but chronic myeloproliferative neoplasm characterized by bone marrow fibrosis.

INCA033989 is a newly discovered high-affinity, fully human monoclonal antibody that selectively targets mutant calreticulin-mediated oncogenesis. It functions as an antagonist to suppress thrombopoietin receptor signaling induced by mutant calreticulin.


A study to evaluate INCA033989 administered as a monotherapy or in combination with ruxolitinib in participants with myeloproliferative neoplasms. US National Library of Medicine. Updated July 7, 2023. Accessed July 11, 2023.

Reis E, Buonpane R, Celik H, et al. Discovery of INCA033989, a monoclonal antibody that selectively antagonizes mutant calreticulin oncogenic function in myeloproliferative neoplasms (MPNs). Blood. Published online November 15, 2022. doi:10.1182/blood-2022-159435