juliej wrote:Thanks, Tom! I love hearing they are starting to work on MSS CRC. Surely one of these immunomodulatory combos will hit the mark! All it takes is one (even partial) success to point the way for others!
Question: Do you know anything about the new Pfizer study combining avelumab, utomilumab and OX40? That's a lot of immune manipulation! Is the point to test the limits? I know avelumab is their PD-L1 inhibitor (there are a whopping 14 avelumab abstracts at ASCO 2016!), but what are the other two?
I first learned of this planned trial a few days ago. It is aggressive (combining the PD1 inhibitor to remove the brakes on the immune system and two drugs (targeting OX40 and 4-1BB) to push down the gas pedal to activate the immune system.) I think this is the first trial to combine 3 "modern" immuno-oncology drug mechanisms. I think one of their goals is to push the limits to see what is possible (the safety aspect of a Phase 1 trial) - but they must have animal toxicology data indicating the possibility of a safe combination + in-hand clinical safety data on 2-drug combinations giving both them & the FDA sufficient comfort to give it a try. Their efficacy goal would be to improve upon existing 2 drug combinations (some combination of: higher response rate, longer durability, achieving responses in "tougher" cancers which are more resistant to immunotherapies).
I am sure there will be more 3-drug combinations starting up, it is the next logical conclusion to try to push the technology to more cures. Safety will be the concern and closely monitored.
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