CDK 12 mutation and Immunotherapy

[MikeMartin]

Hi All,

My PSA as is starting to rise on Arbi/Dexa. I have the CDK12 mutation which is apparently known to be a drug target or to predict sensitivity to Atezolizumab (Tecentriq PD-1 Checkpoint Inhibitor), hence there is open Immunotherapy trial called BoB (NCT03767075). I meet the trial doctor next week.

I also found an ongoing trial immunotherapy trial IMPACT (NCT03570619) which combines other drugs used for immunotherapy with CDK12 (ie: Nivolumab and Ipilimumab)

Has anyone here in the community had success on either of these trials? For the moment I'm not yet convinced that this is the best "next step" for my Prostate Cancer.

At what point should i really drop the ARBI/Dexa? For the moment my Oncologist has given me another 4-month supply whilst I look around at trials

[Tall_Allen]

IMO, abemaciclib is more promising for CDK12 than immunotherapies. There is this clinical trial in France:

classic.clinicaltrials.gov/...

[spencoid2 in reply to Tall_Allen]

I don't understand how it is determined that PC is still castrate sensitive if PSA is rising under ADT? This trial is only open to castrate sensitive people.

[MikeMartin in reply to Tall_Allen]

Hello Tall_Allen,

Thank you for your reply. In addition to what you mentioned, I also found a trial with Darolutamide and Abemaciclib at Dana Farber. classic.clinicaltrials.gov/...

So I have written to the clinical trials co-ordinator at both sites.

To note:

1) The meeting I have on Tuesday is at Gustave Roussy and its call a Basket of Baskets trial - Arm 1G. I suppose they look at repurposing where certain mutations are present.. Here is the link

classic.clinicaltrials.gov/...

2) My PSA has been bouncing around from 6 last Jan to 35 today and my oncologist just prescribed another 4 months of Arbi with Dexa!

[Tall_Allen in reply to MikeMartin]

I thought you were in France. If you can come to the US, there are many clinical trials of abemaciclib, ribociclib, and palbociclib. Abemaciclib is available for breast cancer under the brand name Verzenio, so it is available from your oncologist off-label. Here is my list of current clinical trials:

clinicaltrials.gov/study/NC...

clinicaltrials.gov/study/NC...

classic.clinicaltrials.gov/...

clinicaltrials.gov/study/NC...

clinicaltrials.gov/study/NC...

clinicaltrials.gov/study/NC...

clinicaltrials.gov/study/NC...

[j-o-h-n in reply to Tall_Allen]

You're a freaking angel in disguise.......

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 01/14/2024 7:18 PM EST

[MikeMartin in reply to j-o-h-n]

Thanks Guys! I will look through the links. Yes I am in France and yes I could go to the US as well.

What could be interesting is to find a direct Inhibitor of CDK12 and add it to a PARP inhibitor and/or Checkpoint inhibitor combination.

This mutation is apparently present in 7% of prostate cancer patients, I wonder how many people in the forum actually have it..

[JolleySprings in reply to MikeMartin]

My husband has CDK12 mutation 😩

[JolleySprings in reply to MikeMartin]

How did your meeting go for the Basket of Baskets Trial

[MikeMartin in reply to JolleySprings]

Well Goustave Roussy is pretty thorough! They want to do their own gene testing on the both the original biopsy from Dec 2020, and another circulating tumor test. If there is not enough evidence to go on they will biopsy the tumor itself. I should get a feed back in 2 or 3 weeks if there is confirmation otherwise, I'm Ok to do another biopsy. It would be nice to have a forum specific area. There is more interest in targeting CDK12 recently and some evidence from Marsden and GR that some PARP inhibitors might make a difference with ENZA

[JolleySprings in reply to MikeMartin]

Has anything changed with your treatment plan with regard to CDK12?

[MikeMartin]

They did another FD One Liquid biopsy and found traces of CDK12. But for the BoB eligibility they’ve asked my primary care provider to do a new biopsy as the original does not have enough material. I’m OK to do this but seeing the comment from Tall_Allen and doing further research I am questioning a little whether Tecentriq on its own will make a difference with this mutation

[JolleySprings]

Any progress with your treatment plan for CDK12 mutation?