CALR Trial (INCA033989)

[Zeppelin11]

Is anyone currently participating in this trial? I'm a low risk ET+CALR patient and my MPN Specialist (Dr. Gotlib at Standford) just informed me that I could be eligible for this trial because I have an intolerance to Hydrea. I've been doing some research on it and I was hoping I could find someone currently in the trial. Thank you

[Threestreams]

I would be interested to read about the trial .. I am in New Zealand .. ET with CALR … just had my hydrea increased ..

[Zeppelin11 in reply to Threestreams]

classic.clinicaltrials.gov/...

[Threestreams in reply to Zeppelin11]

Hello .. thankyou very much for sending this link . I have read it and am I correct that it is only for those living in the United States .. however I have seen further in this link someone from the United Kingdom. I will check with my specialist . 🙏Trudy

[ETket]

I've been offered a place on it (in London) and they are hoping to start the screening process in May.

[Threestreams in reply to ETket]

I have just read the link and thought I would have to be in the United States .. is this not correct?? I will ask my specialist . I look forward to hearing how you get in .. thank you 🙏 Trudy

[ETket in reply to Threestreams]

In London they told me that they were recruiting people for the study from various anglophone countries. There is no harm in asking your specialist if you would be eligible.

[Mtnlife]

My doctor and I have discussed. Right mow I am on hydroxyurea and all blood counts are at goal. I have no side effects from the medication and feel very well. So it is not for me now but may be in the future.

[SoledadBarcelona]

What kind of trial is it?

[ETket in reply to SoledadBarcelona]

Monoclonal antibodies delivered by a drip. My local hospital referred me to London because I have tried Interferon (my liver did not approve), Hydroxycarbamide (no longer very effective) and Anagrelide (gives me heart palpitations twice a day). I am currently on a combination of Hydroxycarbamide and Anagrelide and my platelets are in the 800s. I have had one minor historical clotting event.

[SoledadBarcelona in reply to ETket]

Interferon here.

koreabiomed.com/news/articl...

[SoledadBarcelona]

link.springer.com/article/1...

[LongETinUS]

Gotlib should be able to explain what it is, how it works and the risks.

I think there isn’t much out there to find because it is new and the phase 1 trial is only just beginning. Phase 1 trials are generally to test safety of the new drug in humans. Clinicaltrials.gov indicates that they are looking to test the safety at different dosing levels, and some other matters.

Other than general info on immunotherapies this is about all I could find on it.

Discovery of INCA033989, a Monoclonal Antibody That Selectively Antagonizes Mutant Calreticulin Oncogenic Function in Myeloproliferative Neoplasms (MPNs)

ashpublications.org/blood/a...

I'm sure the community here would be grateful for any info you find as you proceed.

[EPguy]

I see you're on Anagrelide. Has Dr Gotlib discussed the trade offs with this agent?

The trial is a good opportunity. It seems promising as below:

" the antibody suppressed the mutCALR-induced accumulation of megakaryocytes in the bone marrow, a hallmark of essential thrombocythemia. The targeting of mutCALR disease-initiating stem cells was confirmed by the lack of disease development upon secondary transplantations."

That last part means the treated mouse had marrow so clean of mutations that it could not "infect" a fresh mouse. This is a known test in MPNs that is not easily met. This is all for mice, the trial you're looking at is phase 1, so 1st time in humans, not as proven as a phase 2 would be. That is a consideration.

ashpublications.org/blood/a...

This is does not seem to be the new molecular Car-T therapy that "cures" CALR, but still it looks quite promising. As with the molecular therapy, this method identifies mutant calr; this approach is not yet possible for Jak2.

[Zeppelin11 in reply to EPguy]

Gotlib said it was a really good opportunity but we are going to discuss it further because he wants me to know exactly what I'm getting into (if I get approved). They recently broadened the criteria so I'm back in the running. I'm currently on Anagrelide and deal with fatigue, digestive issues and heart palpitations a few times a week. I'm only 39 and have a family and business so I want to make sure I know exactly what I'm signing up for and if it's a good idea to participate in phase one. Do I wait and gain more insight, or could this be the opportunity I've been waiting for? Clearly I need to chat with him more in order to make my final decision.

[EPguy in reply to Zeppelin11]

"could this be the opportunity I've been waiting for?" Yes, this possibility is motivating the sponsors. But - Is it worth the risk? With low risk ET you do have a decision. I assume there are zero humans so far have tried it.

I see the study is planned to end late 2028. One option could be to hold off while others, presumably with more urgent conditions, get time on the medicine. Catch is getting in before they fill recruitment.

It is a quite large phase1, n=140, suggests the sponsors feel it's promise is worth the expense.

By broadened you likely mean to lower risk pts. One question is whether some new info pointed to reduced risk and allowed them to feel comfortable with that.

Either way it's great you alerted the forum to this possible future option. To actually remove the clone would be an advance and now we know it might work by two very different solutions. (all limited to calr for now, there have been posts on progress to expose Jak2 for these Tx too)

[dbus1417]

please keep us updated on what you choose. I am in a similar boat if my liver numbers don’t come back down to earth on interferon.

My hematologist has expressed trying rux or trying this trial. I am praying things work out for you whatever path you decide.