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Okay Melanoma gurus, who has heard of this?

Okay Melanoma gurus, who has heard of this?

Posted By
ScaredPartner
2/10/2020 4:34pm
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Replies: 7

Hello all,
Had the most amazing consultation with a new group of doctors this morning looking for a new way to save my partners life.
I try my best to stay on top of new treatments, but the one they offered this morning was something I haven’t heard of yet, and I can’t find the trial number when researched.
TCD14678

This will be a phase 2b trial, not officially opened yet, but within the next week.
It is a PD1 combined with a CDK 6/8 inhibitor.
The idea sounds great, but it’s the unknown.
I believe the pd1 is cemiplimab which I haven’t seen use of in melanoma specifically yet.

Do any of you have any info on this?
This is of course a trial after he progressed on the usual ipi/nivo, and now targeted as well.

Just looking for anything at all.

Thanks!

Hi there Scared Partner, cemiplimab (Libtayo) is made by Regeneron Pharmaceutical and has been tested in Squamous cell carcinoma (see following link to trial and Regeneron). Link to CDK 4/6 inhibitors not my area of research so not sure what the difference would be for CDK 6/8!!! https://www.targetedonc.com/news/phase-iii-trial-investigating-adjuvant-... https://www.regeneron.com/pipeline https://www.cancer.gov/about-cancer/treatment/clinical-trials/interventi...

Here is a link to CDK 4/6 inhibitors, not sure if it is helpful since you are looking for CDK 6/8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315195/

Thank you, Ed.
As far as I can gather it seems as if the CDK8 is something they are seeing expressed in aggressive melanoma, and so they are trying to target that.
The way it was explained today was that this trial is meant for people who showed response in some, but not all areas of the body within the first 12 weeks on something like an ipi/Nivo. The immunotherapy took down much of the tumors including all brain Mets, but he still had some progression in bones, and soft tissue.
We were told this is a trial that they’re using to determine if this new inhibitor combined with PD1 could be the key for the other 50% of people who don’t respond to immunotherapy.

I really can’t find much information on CDK 6/8 in melanoma and how it was determined why it makes sense to target that in this trial, but since I hold no medical degree I am going to have to trust those that do.

I just wish I had more information. Information brings me peace of mind.
We are using this in hopes we won’t have to try TIL, but that’s a gamble too. The longer we wait on TIL, the worse off he’ll be when he starts that horrendous round of treatment.

With TIL's at least there is a track record of success and depending at what location there are some new approached being used, also Lag-3 has been tested in patients that have progressed on immunotherapy as well as TLR-9 injectables have been studied for a couple of year now. NKTR-214 + Nivo, T-vec + ipi or T-vec plus pembro have also been studied in trials. When Dr. Jason Luke was at Chicago hospital they were doing a lot of research of adding targeted radation to solid tumors with immunotherapy with the thinking that the radiation would increase the antigen presentation to the t-cells so cold tumors might become hot again with t-cells getting into tumor microenvironment. There are a lot of options that seem reasonable versus something you can't find any information on. Just saying!!!https://www.youtube.com/watch?v=F2ukKO2IPrk https://www.youtube.com/watch?time_continue=3&v=kvyPL5W9ZTA

Given the tag you noted, I found it linked to this trial: https://clinicaltrials.gov/ct2/show/NCT03192345

However, this trial pairs SAR439459 (which i apparently a monoclonal antibody (mAb) directed against human transforming growth factor beta, rather than a CKD 6/8 inhibitor) and Cemiplimab. So I doubt that it is what you are looking for at all.

Like Ed, I have a fair number of reports on CDK 4/6 inhibitors, but no intel on CDK 6/8. Here is a nifty diagram of where CDK mutations play out in the melanoma pathway: https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2017/06/asco-... Though CDK 6/8 is not noted, I would presume it falls along the Cyclin D path.

Not sure all that helps you very much. Your partner is lucky to have you in their corner. Hang in there. celeste

Well, I still can’t find the actual trial anywhere, but after looking over the paperwork we left with on the trial, it clearly states this has more to do with TGFbeta.
This beta thing seems like a rather fickle character in tumor growth. It both aids, and suppresses based on how advanced cancer is?
Again, I can’t find much on the TGFbeta as it seems like most studies I’m reading are from around 2017, and didn’t involve any human trials yet.
The idea sounds interesting, but being one of the first human lab rats is a bit terrifying.

Ed, or Celeste, do either of you have any insights or opinions on this concept?

Thank you again,

Hi
Can’t help too much on the specifics of CDK6/8 but I am on the Platform trial combining Spartazimulab (PD1) & Ribociclib (Cdk4/6) and has 3rd cycle on Tuesday. So far doing ok and gut feel is to get stable disease on scans booked in a few weeks time. Been ok with side effects so far although latest bloods show a drop in White Blood cells that may lead to a treatment break next time.
Hope you have some success
Mark