CALR Antibody Trials – UPDATED by CT New MEMBER

[sydunipete]

Here's a roundup of recent information on two groundbreaking CALR Antibody trials. The trials are available in Australia (but not NSW - I'm not sure if you could participate by travelling to an interstate doctor). The early results look extremely positive.

NB. There are two trials - both in Phase 1 I believe: INCA033989 (https://trials.cancervic.org.au/details ... ct05936359 and https://ashpublications.org/blood/artic ... c03Q4hM_Gw) and one from A/Prof Daniel Thomas (https://www.leukaemia.org.au/stories/an ... discovery/) This is an early paper, unfortunately I can't find more up to date information.

This from one participant:

in my 6+ month phase 1 study INCA033989 (monoclonary CALR antibody) came back after MRI and KMP and they sound really good.
MRT:
- Mucus volume reduced from 319 ml to 240 ml (that's about 25%)
- Liver volume reduced from 2125 ml to 1675 ml
KMP:
For example, I have compared some text passages in a dot way here and highlighted the changes.
- Megakaryocytes changed from "heavily multiplied with size variation" to "single size variable"
- eosinophilic granylocytes changed from "mild reproduction" to "no reproduction"
- Fibers changed from "significantly reproduced" to "slightly reproduced"
- Vessel mesh changed from "significantly compressed" to "slightly compressed"
- Megakaryoposis changed from "atypical, abundant cluster education" to "normal, without cluster education"
- Fibrosis degree changed from "2" to "1"
Overall, these results with improved blood work and reduced symptoms, this is more than I had hoped for after a little over half a year.

and another:

so far 2 weeks after one treatment my platelets went down from 1.2 million to 385,000. I was shocked to find how quickly they came down. I haven’t had any major effects.

[MPN-MATE Admin]

Once again Pete ...

A highly informative piece of research information... One of our newer members "Aly" is participating in those Phase 1 Trials in the USA, I believe and has promised to keep us appraised when possible etc.

Results do sound most promising thus far... Naturally, myself as a CALR2 person, I will observe w/ great interest as things continue to progress...

Thanks so much for bringing your latest two (2) Posts to MATES Pete...

That's what our site is always in need of... More and more useful & relevant MPN research & information.

Cheers

Steve
MPN-MATE RF

PS. Hope to see you Sundat at the special Cafe Catchup...

[birchshores]

I'm newly enrolled in the US (Incyte) CALR monoclonal antibody trial. I've only had three treatments and saw dramatic results after the first (they test you very frequently in cycle 1).
I can confirm a drastic reduction in white blood cells, platelets and LDH with no side effects other than lots of pokes for tests and infusion.
I'm really hoping to see my MF-3 decrease eventually as well, which my doctor and Frank confirmed can be expected.
I still have a lot of questions about the monoclonal antibody trial like, why are they increasing the dose when they're getting results? Are they hoping to induce remission?
Despite all the travel, time and pokes I'm very excited about the trial and would encourage anyone who has access to see if they can participate.

[MPN-MATE Admin]

Hi there Birchshores...

Firstly, wishing you a very warm Welcome to MATES... (Ever so glad you've found us...).

You are in fact now the 2nd CALR "mono-clonal anti-body" MPN patient to advise me/us here in Australia about their experiences thus far in the INCYTE version of this Clinical Trial.

It is exciting to hear of your promising progress thus far, and especially so that there are yet to be any adverse / side-effects of any description being mentioned.

My name is Steve, I am also Post ET / MF w/ CALR(2) as my mutation Driver, w/ ASXL1 mutation as well... Hence, I have long been aware that the CT was coming, and there is another similar version taking place here in another state in South Australia. Unfortunately, I am located thousands of kilometres away in New South Wales on Australia's East coast. At one stage, there was hope that the Trial would also be conducted here but it did not eventuate.

My own main concern was that I wanted to be able to request the ongoing "input & output data" in real time, so that i'd have a better understanding of what was transpiring to me in "real time" and I was told that would not be a possible.

Nevertheless, I am most grateful to be learning about yours & Aly's CALR "mono-clonal anti-body" CT experiences thus far and naturally would love to keep hearing from you in this regard...

No doubt, everyone here at MATES, and especially those w/ a CALR mutation would obviously be wanting to know everything about the brave efforts of you and many others who are presently going through this, CALR "mono-clonal anti-body" CT, in the hope of finding better alternatives, and possibly even a "complete remission" or CURE!

Please do keep us all informed as you continue through the CT Birchshores... Thank you so much!

Yes, also very interesting that they want to increase your dose, while you seem to be doing so well... (Makes me curious as to why too...)?

Please stay in touch...

Thank you for finding us and sharing your results thus far, I for one am really looking forward to your next results report, whenever you have more to share with us here in Oz...

Very best wishes for a happy & most promising festive season & New Year... for you & yours...

Steve
MPN-MATE RF Admin

PS: Birchshores... Found a picture Avatar for you, you can change it at anytime to one of the other stock images available... Thank you again... Steve

[birchshores]

Thank you for the warm welcome, Steve. I'll be sure to post here when I have interesting follow up info.
Sorry to hear you can't be in the initial Australian phase, but hopefully they'll expand to your region for phase 2.
Take care!

[sydunipete]

I had a Facebook chat with somebody on the trial asking how it was going. Her response:

"so far it’s going well, all other numbers apart from the ferritin [low] are looking good. My platelets went from 1.2 million to 375,000 after only 1 treatment. I’m still waiting to see my recent numbers."

I believe (but I can't find out where) that a paper on the trial is being presented at ASH 2024 (which concludes today) so hopefully some more information will be available online soon.

I can explain the reason behind the dosage increase. An aim of Phase 1a is to identify the maximum tolerated dose. "In the Dose Escalation Part (Part 1a), people with MF and ET will receive INCA033989 as monotherapy, which will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s])." (Source: https://trials.cancervic.org.au/details ... ct05936359)

I'm meeting a SCT specialist on Friday and want to be equipped to ask the question because I may have to choose between 1) do nothing, 2) SCT, 3) drug trial such as this one. Hence my interest.

[MPN-MATE Admin]

Hey Pete...

Great to be hearing from you again...

Hopefully, "Birchshores" is keeping tabs to also understand, "...why her doses have been increased etc...?"

Me, I am struggling a tad at the present, with more than my usual aches & pains, and especially so given the seasonal time of year... Usually, this is the time I suffer least from bone / joint pains, cold sweats, temperature flushes, mind fog, and even the return of some pruritus, (highly unusual!). Today, I suffered from a very rare side-effect "Shortness of Breath". Very weird indeed, as it's been a really long time since I can recall when that effect ever transpired(?)

I've decided that I may well undergo yet another BMB some time into the New Year(?)

Been closely monitoring my bloods, and apart from my Platelets being in the low 800s range, my WCC is extremely low (placing me at higher risk of a multitude of infections), even with the anti-viral. Otherwise, my Reds are low borderline, same with Hgb & Hct. Iron is ok atm... LD is always on the high side...

Try to stay as protected as possible by observing ALL the usual safety protocols etc.

Anyways, hope you're travelling ok Pete, and my very best to you & yours for the coming festive season...

Stay happy, healthy & safe!

Best

Steve

[sydunipete]

Steve,

I'm sorry to hear that you're not travelling so well at the moment. I hope you bounce back quickly.

I met with the transplant specialist and that went as expected. I'm not too keen on the idea but he was very supportive of the trials and he recommended I get in touch with them so I'm reaching out at the moment. If anybody has contact details for the David Ross trial I'd appreciate that - I seem to be hitting a brick wall.

I'm still doing ok and I wish you all the very best for Christmas and a happy and healthy 2025.

[MPN-MATE Admin]

Hey Pete...

Thanks for your Post... I'm ok BTW... Just the usual stuff really!

I seem to recall, that the CALR CT is ONLY available if you are located in SA... (?)

I have David Ross's contact details & I'll therefore try to ask him, where the CCT is up to atm, if you like...?

Would you be willing to relocate in order to participate in the Trials?

Won't be all that long before they consider Phase II, although I am uncertain as to the timing atm...

Originally, when I first spoke with David Ross, and he joined one of our meetings, another colleague was supposed to take up the Sydney leg of the CCT. However, & unfortunately that did not happen, for whatever reasons(?)

Happy to ask on your behalf all the same Pete...

Best wishes

Steve

[sydunipete]

Steve, thanks for following through with David Ross on my behalf. Just to summarise recent discussions for the benefit of others and some of this information may be more accurate than others.

The trials seem to be run by Peter Mac in Victoria and Royal Adelaide Hospital. I spoke with RAH and they were very helpful.

To be admitted to the trial you need to meet a number of criteria as shown on the trial website but also have an enlarged spleen (>650mm from memory) and patients with MF have to be on ruxolitinib with a suboptimal response or have tried and discontinued ruxolitinib or be considered unsuitable for ruxolitinib treatment.

It seems like the treatment consists of infusions weekly for 1 month then monthly for 5 months (so 6 months in all). Obviously there will be a bunch of measurements including spleen ultrasounds and several BMBs along the way.

The process is you submit a letter from your specialist confirming you are CALR+ and some general background, you attend a 1 day screening and if accepted on the trial you must commence within 28 days.

Would I consider the trial? Absolutely. I could imagine a serviced apartment in Adelaide for the first month then travel back and forward for the monthly visits.

[MPN-MATE Admin]

Pleasure Pete...

Please keep us all informed should you decide to follow that route, with the CALR Clinical Trials (CCT). They are also doing the same recruiting at the Alfred in Victoria, according to the link provided by Ass Prof. David Ross etc.

Hopefully, come mid 2025, such a CCT might also start recruiting here in Sydney?

Best wishes

Steve