Steph20021 wrote:Very cool. DK do you see any hope for us MSS non-mutants anywhere down the pipeline?
Yes I do!
- First of all, with this combination (MEK + PDL1) they have not tested it in KRAS-wildtype patients so it may have some level of activity in those patients too. There is no clinical activity saying one way or another. There are KRAS-wildtype models where it does work (published)
- Scientists strongly believed this would be true all along - cotherapies would be identified with MSS-CRC clinical activity. As I have said on Colon Talk continuously, there are just "too many shots on goal" with strong animal model data for them all to fail.
Clinicians and patients are now seeing this. A match has just been thrown on a Hope gasoline puddle. today's results also implies (logically) that there will be additional co-therapies which will work. It is illogical to assume that only a MEK inhibitor will work (as an outlier). The immune system wants to attack MSS-CRC… you just need to cycle through enough appropriate co-therapy drugs to find out the right combination. Maybe KRAS-wildtype needs a different co-therapy - well multiple different co-therapies are in clinical trials or approaching them quickly as we speak. I firmly believe it is a solvable problem – we’re not talking cold fusion here.
I think this will probably open up the flood gates at other companies for significantly more MSS trials. More trials will be started now since they see that a co-therapy CAN work in MSS-CRC, similar to what happened at ASCO-2015 when seeing MSI-high PD1 activity opened up many more trials for them. MSS-CRC is a BIG patient population… companies like that, especially once de-risked a bit by today’s study results.
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