INCA033989 phase 1 clinical trial is recruiting patients

[flamboyant_hawking]

Source: rarediseaseadvisor.com/news...

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.

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 completed 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.

[CanadaG]

thank you for posting. This is an exciting treatment targetting CALR. I was wondering when they would begin trials

[Skye333]

Hi this sounds exciting. I have done other trials and I wouldn’t mind having a go at this one as long as my Haematologist is happy with it.

[BlushNoisette]

Hi,

I participated in the Majic Study 2015 to 2020. Ruxolitinib was compared against best available alternatives. I was lucky and being in the Rux treatment group I had a chance to see whether it suited me. And it really did, thank goodness! Novartis is still supplying it to me, via my hematology team, free of charge on compassionate grounds.

I have been extremely fortunate. I would encourage anyone who is thinking about participating in a study to to find out as much as possible and then do it. I applied with the help of my local haematologist and the at the study centre, the haematologist explained in detail both the pros and cons of participating. There was no pressure on me to sign-up so I had time to consider it before signing the paperwork.

[welshhuw]

Thank you for posting this exciting research ! I was diagnosed with mCALR type 2 (5bp ins) some years ago and have been following developments closely. I was aware that a research team in Australia had identified a monoclonal antibody that selectively binds to mCALR but wasn't aware that it had progressed to clinical phase 1. Exiting times......fingers crossed for a positive outcome.

[CanadaG in reply to welshhuw]

I believe the Incyte anyibody is a different antibody to the one discovered in Australia. Hopefully there will be more than one option available

[welshhuw in reply to CanadaG]

I guess having more than one monoclonal antibody candidate that binds to mCALR is another positive. I wonder if the one discovered by the team in Australia will progress to clinical phase I, probably dependent on clearing the necessary pre-clinical testing. I did access the INCA033989 study on the clinical trials website, seems the study is not due to report until 2028, lets hope all goes well.

[dbus1417]

let’s gooooooooo 🙌🏽

I pray this is successful. How awesome would it be to nip this mpn in the bud while I’m still in my 40s. 🤜🏽

How long does it typically take before something like this is ready for prime time??? 🤔

[CanadaG in reply to dbus1417]

that's a good question. I suspect that it will take a few years and stages of clinical trials before it receives full FDA approval. It's a public company that is doing the trial so they will likely publicly disclose progress and expected timing periodically