A new immunotherapy trial has been announced open to BOTH MSI & non-MSI (MSS) CRC. Also of note, it does not exclude for prior PD-1 use.
It is a combo therapy with a drug called "CPI-444" which targets the "adenosine-A2A receptor" which is believed to potentially cause immunosuppression in "cold tumors". This will be the first trial testing this strategy (so no human data yet) - but it is a strategy where multiple companies will probably be testing in 2016 based upon animal model data.
Adenosine-A2A receptor drugs have been tested for other uses before and as a drug class, they have had a good safety record although I do not know if this exact drug has been tested before.
They're betting big on this trial - as a Phase 1 trial, they are shooting for 544 patients across 8 tumor types. Locations have not been announced yet.EDITS TO ORIGINAL POST:
Thank you to JFrog for pointing out (actually in a post yesterday I missed!) that this trial is RANDOMIZED so at least to start, 3/4 of patients get the experimental drug alone - 1/4 get it as a combo with a PD-1 inhibitor. There are a lot of pre-clinical papers on this target, although to be honest I'm a bit surprised they are betting so big on single agent - I'm curious (but don't know) their internal data which prompted them to set up the trial in this way.EDITS TO ORIGINAL POST #2:
I did some more digging on CPI-444 just because its Phase 1 clinical plan was SO ambitious (4 dose cohorts, 8 tumor types as a Phase 1), I wanted to figure out what the heck their story was...
Here is their SEC filing from last week: https://www.sec.gov/Archives/edgar/data ... 67zs-1.htm
The molecule was previously found safe in healthy volunteers for (unfortunately failed) Parkinson's Disease development, reducing safety risk. Although it is VERY important to point out that it is MUCH easier to successfully treat cancer in mice than in humans... (if we were mice instead of people we wouldn't be in Colon Talk right now!) they have seen significant activity in some CRC mouse models even as a single agent (even better with PD1 combo) - which explains why they are trying both single agent & PD-1 combo in the Phase 1 clinical trial.
For anyone who wants to get far down into the data p81-p90 of the SEC link = their preclinical CRC mouse data & clinical development plan.
Once again, I want to strongly point out that cancer is much easier to treat in mice than in humans so there is far from a guarantee of human activity - but I think taken together: the safety aspect, plus their mouse model data (plus heavy competitive pressure) explains why they are planning such an abnormally big Phase 1 trial.https://clinicaltrials.gov/ct2/show/NCT ... 822&rank=1
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/2016 Colondar 2.0 ModelDK37 Science Posts List