The Colon Club

For those of you that are on Keytruda (pembrolizumab), and met the mutation burden threshold after taking the Foundation One Test, are you technically on a "clincal trial" while being treated with Keytruda?

My mother is currently on Stivarga, which seems to be keeping most of the mets under control. But a new lymph node met popped up on a scan in july, and stivarga does not seem to work for that one node. The staff at our clinic hinted at clinical trials at UCSF, but didn't mention anything about Foundation One Test or Keytruda, as our onc is on vacation. We won't get the see the onc until late August.

I need some suggestions on what I will discuss with our onc at the next appointment. How do I go about mentioning to the onc about the Foundation One Test for mutation burden, if the onc himself does not suggesting trying Keytruda?

Meatie

Hi Meaty,

I’m not on Keytruda, but I simply asked my oncologist whether he could order TMB testing on my retained biopsy, to see whether I might be a candidate for immunotherapy. He said he would be happy to do if but I’d have to pay for it out-of-pocket, as neither public nor private health funds in Australia cover this level of testing yet.

If your mum is already on Stivarga, there are some fascinating new results released at ASCO this year combining this drug with Keytruda to elicit a response in even MSS/low-TMB patients. You may hence also want to ask your onc about the results from the REGONIVO trial. Given both drugs are already approved for CRC you could potentially access them now outside of a trial, although I don’t know about funding for the Keytruda (e.g. it’s not funded for MSS here yet).

Good luck,
Rob

So, the next time we see the onc, I should just directly ask about Foundation one testing?

meatie wrote:So, the next time we see the onc, I should just directly ask about Foundation one testing?

Yes that would be my starting point. If TMB is specifically what you’re after, then maybe ask about this - some places can also test for this (other than Foundation One) so they may be able to organise this for you.

Of course you may still end up needing to organise it yourself, but I presume you would still need your onc’s help with access to biopsies etc?

Echoing Rob, if you start Keytruda I would strongly consider staying on regorafenib based on the Regonivo results.

Pyro70 wrote:Echoing Rob, if you start Keytruda I would strongly consider staying on regorafenib based on the Regonivo results.

Is there a similar trial that uses Ketruda in place of opdivo?

Meatie are you looking for a trial to participate in, or for results?

And apologies - you’re correct and my earlier post should associate Opdivo with REGONIVO, not Keytruda. Both are PD-1 inhibitors though of course.

Rock_Robster wrote:Meatie are you looking for a trial to participate in, or for results?

We would like to participate in a trial.

meatie wrote:

Rock_Robster wrote:Meatie are you looking for a trial to participate in, or for results?

We would like to participate in a trial.

No problem. Below is a link to a Phase I/II trial that is yet to start recruiting in 3 centres...
https://clinicaltrials.gov/ct2/show/NCT03657641

I’ll post more if I can dig anything up.

I’d also comment that as both drugs are already approved for CRC you should be able to access them outside of a trial, although I don’t know how funding would work for the Keytruda.

I haven’t found anything further for that exact drug combo, but there are some other trials using Stivarga and other PD-1 inhibitors (i.e. other than Keytruda and Opdivo). Just let me know if this is interesting.

meatie wrote:

Pyro70 wrote:Echoing Rob, if you start Keytruda I would strongly consider staying on regorafenib based on the Regonivo results.

Is there a similar trial that uses Ketruda in place of opdivo?

Hi Meatie,

Yes Merck is trying Keytruda with regorafenib in the trial NCT03657641. As i mentioned, in theory Pembrolizumab (Keytruda) and Nivolumab should be interchangeable, but as of now there is no data for the Regorafenib + Pembrolizumab combo.