The Colon Club

New trial at NIH (Bethesda, Maryland)
* #NCT03050814
*UPDATE March 20th: RECRUITING

*Only for MSS CRC

*Only for UNTREATED MSS CRC (recently diagnosed)
*Randomized (but "Arm A participants can join Arm B").
*FIRST, it will be "A LEAD IN COHORT, comprising THE FIRST 6 EVALUABLE SUBJECTS ENROLLED".
* Arm A: Ad-CEA vaccine + Avelumab (anti PD-L1) + standard of care
VS.
Arm B: standard of care
*"Standard of care" means: FOLFOX + Avastin; later, Xeloda + Avastin

Meaning, the arm A gets two immunotherapies --Avelumab, a PD-L1 antibody plus an adenoviral vector vaccine against CEA--- ADDED to standard of care. And, as said, it indicates "Arm A participants can join Arm B".
*NCI-17-C-0057 (NCI Protocol ID)
Investigator: Austin G. Duffy, M.D. Referral contact: Diana Martin, R.N. diana.martin@nih.gov... 301.451.2163 301-496-9574

https://clinicaltrials.gov/ct2/show/study/NCT03050814

And that should show to any oncologist how immunotherapy trials are NOT the last resource.

This one is very interesting.

I cannot believe how fast the immunotherapy is progressing. It is changing cancer world...

I also like the
A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors for CEA expressing tumors.

Please delete-duplicate

mariane wrote:This one is very interesting.

I cannot believe how fast the immunotherapy is progressing. It is changing cancer world...

I also like the
A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors for CEA expressing tumors.

What is the NCT # of this trial with RO695688?? I read in Julie's recent blog that she will be starting it.

It is Julie's trial. I checked.

Tom in UK was on it and responded well. He stopped responding but it gave him time and shrinkage of most mets.
I liked the description of that since Maia posted it here in November or December. In December Tim posted very encouraging news. It stopped working for him but the duration of response may vary.
Immunotherapy shows various grade of response on tumors most likely from the heterogenity of mutations status. Each tumor may vary genetically. Tumor are also genetically unstable with their constantly dividing cells. New mutations are being created all the time. It is how I see it.

Maia surely knows more.

Steph20021 wrote:What is the NCT # of this trial with RO695688?? I read in Julie's recent blog that she will be starting it.

It's #NCT02650713
A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors

https://clinicaltrials.gov/ct2/show/NCT02650713
Yes, our Julie is starting it. Everything crossed for her!
(you can get more information if you put the trial number in the clinical trial finder in my signature)
BTW, there is a trial ongoing with the RO688 (the nickname of the drug) as monotherapy: https://clinicaltrials.gov/ct2/show/NCT02324257

Tim had progression, apparently. But it worked during a while, even on his BRAF mutated CRC.
Robert, other patient on that trial, at MSK, continues doing well --reported a couple of weeks ago.

I am curious how mutation status influences immunotherapy. How BRAF influances response? Melanoma has BRAF and responds well. We know -the more mutations, the better- that's why MSI respond.
We know how some mutations influence chemo response.
Do you know how common known mutation status influences immunotherapy?? Some "bad" mutations may not be bad as a target for immunotherapy (?????)
???????

So far, not data about the more common mutations (RAS (KRAS and NRAS), BRAF, p53, PIK3, APN) being pertinent for (good or bad) response to immunotherapy.

Thank you Maia! :)

mariane wrote:Melanoma has BRAF and responds well. We know the more mutations

No regarding immunotherapy, but wanted to point out that he BRAF mutations act different in melanoma than in CRC, that's for sure: MEK inhibitors work well against BRAF in melanoma, not well for BRAF CRC. Only recently there is a triplet that show some activity.
The common mutations i mentioned above are part of a "different system" of mutations than those called "microsallite status". Only those of this system (MSS vs MSI) seem pertinent for prediction of response to immunotherapy (at the moment... who knows in some months : )

MSI - have constantly mutating genome/unstable genome - so their mutations are easy target since they have thousands of mutations.

I need to read more from newer publications if find something for free. What I know is old....

Why is melanoma highly immunogenic? I have never dedicated time to research it...

I know that BRAF in crc responds only to triplet therapy at this point.As I suspected we do not know much how mutation status influences responses to immuno. There will be statistics soon whenever we will see more positive trials.
We still know little.

It is fantastic, exciting time for scientists. Great for the patients as well.

Updated the starter post since the trial is now

RECRUITING.

If you are recently diagnosed, Stage IV, I'd recommend to read and read so you understand what the treatments are proposing you, so that way you're in an optimal position to judge if this IMMUNOTHERAPY trial might be adequate for you.

I love more trials showing up for MSS CRC!

This one is very unusual - Avelumab, a PD-L1 antibody plus an adenoviral vector vaccine against CEA. I'm assuming the vaccine uses the Ad5 [E1-, E2b-] gene delivery platform, which induces more potent immune responses in Ad-immune hosts. This vaccine has shown good results in some very early Phase I trials. And since you get standard of care in addition to the immunotherapy portion, it seems like a good possibility for those newly diagnosed.

Thanks, Maia, for putting this on our radar!

Hugs from your fellow zombie-hunter!!!
Juliej

juliej wrote: And since you get standard of care in addition to the immunotherapy portion, it seems like a good possibility for those newly diagnosed.

Exactly!

Huge hug to you, I'm so happy to see you kicking arses!