The march of immunotherapy advances rolls on - this time with a novel strategy (CCR2 antagonist, PF-04136309), to make a "cold immunotherapy" tumor type hot: PANCREATIC CANCER (CRC not studied but keep reading!). A small study but very encouraging for both pancreatic patients as well as potentially patients with some other "cold" tumor types! There are a lot of biological overlaps between Pancreatic Cancer and MSS-CRC… overall pancreatic cancer is a much more aggressive disease than MSS-CRC.
16 (49%) of 33 patients receiving FOLFIRINOX plus PF-04136309 who had undergone repeat imaging achieved an objective tumour response, with local tumour control achieved in 32 (97%) patients. In the FOLFIRINOX alone group, none of the five patients with repeat imaging achieved an objective response, although four (80%) of those patients achieved stable disease.
Now for those of you that don’t mind getting down into the weeds… I just read the full paper - it was a very well done trial. The clinical biopsy data: Reduction of immunosuppressive immune cells (Tumor associated macrophages (TAMs), Regulatory T-Cells (Tregs) with correlated increased in tumor fighting CD4 and CD8 T-cells. Very nice proof of concept of the general strategy being tried very hard right now to remove immunosuppressive cells like TAMs & Tregs to expand the breadth of cancers/patients responding to immunotherpapies (MSS-CRC we're all looking at you). It was a small trial in one cancer type (but a very tough cancer type, not yet another melanoma paper!) - hopefully it confirms activity in more advanced pancreatic cancer patients and also in additional tough cancers types! More clinical trials to test to come...
Links to full paper & accompanied editorial. No trials open for CRC right now – but… maybe in the future and a great first clinical proof that the “general” “COLD TO HOT” strategy to remove immunosuppression can translate from animal models to clinical data. That is exactly the general route that MSS-CRC is trying to go after…. Keeping fingers crossed for at least one of the CRC trials currently in progress…….. http://www.thelancet.com/journals/lanon ... 70-2045(16
)00078-4/abstracthttp://www.thelancet.com/journals/lanon ... 70-2045(16
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