CCR2 Antag Clinical Immunotherapy Activity Against a "Cold" Tumor Type (Not CRC but Keep Reading!)

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DK37
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Joined: Tue Sep 17, 2013 8:31 am
Location: San Diego

CCR2 Antag Clinical Immunotherapy Activity Against a "Cold" Tumor Type (Not CRC but Keep Reading!)

Postby DK37 » Fri Apr 08, 2016 12:13 pm

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/abstract

http://www.thelancet.com/journals/lanon ... 70-2045(16)00151-0/fulltext

-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
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 Model
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NateA
Posts: 115
Joined: Sun Aug 02, 2015 7:41 pm
Facebook Username: Nathan Drew Allen

Re: CCR2 Antag Clinical Immunotherapy Activity Against a "Cold" Tumor Type (Not CRC but Keep Reading!)

Postby NateA » Fri Apr 08, 2016 2:28 pm

Thx DK! Let's heat those bad boys up!!
7/15 dx CC stage 4 with lots of liver mets CEA 208
KRAS Mutant G12V, MSS.
9/23 from folfoxiri to folfox and Xeloda. CEA 25
11/11/15 all liver markers in the zone, CEA 4.0, moving to Avastin/xeloda for now..tumors shrinking
01/13/16 Avastin/xeloda CEA 3.5
03/11/16 clean PET CEA 4.4

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Nik Colon
Posts: 5210
Joined: Thu Jan 08, 2015 3:35 pm
Location: MN

Re: CCR2 Antag Clinical Immunotherapy Activity Against a "Cold" Tumor Type (Not CRC but Keep Reading!)

Postby Nik Colon » Sat Apr 09, 2016 2:06 am

Thanks again DK!
KRAS-mut G12V,MSS
Stage IVa Sig CC 2 lvr mets 1/12 Ln
(3, =<3 lng spots at dx til 5/16)
=T3N1aM1a 4cmX4mm (lng not included)
dx 12/2014 at age 39
CEA 1/15-4.9, 12/16-4.9 again
neoadj FOLFOX 1/15-3/15 (4tx, 3w/1wo oxi)
Col/Lvr surg 4/23/15 NED
adj FOLFIRI start 6/15-9/15 (8tx, 5w/3wo iri)
1 sml lvr spot/cyst
12/6/16 multi lung spots/mets?
No longer NED :(
My tx ongoing-start 1/20/15
Adding your SIGNATURE, etc

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HopeForJesse
Posts: 245
Joined: Wed Feb 24, 2016 9:39 am
Location: Philadelphia

Re: CCR2 Antag Clinical Immunotherapy Activity Against a "Cold" Tumor Type (Not CRC but Keep Reading!)

Postby HopeForJesse » Sat Apr 09, 2016 7:55 am

Very promising news. Thanks for sharing and keep us posted please.
DH DX 01/16 49 YO inop RC stage IV liver mets
MSS TP53 APC,BRCA2
12/15 CEA 241, FOLFOX to 11/16
LAR/ileo 5/16 Clear margins 1/29 nodes
HAI, reversal, liver resections7/16
FUDR 8/16 -NED 3 mos
Rising CEA 3/17 Xeloda, 5/17 -12/17 Erbitux & Iri stable but lung/lymph mets CEA 2.7
4/18 CEA 87 :( 5/18 5 days SBRT radiation to sternum CEA declining again 6/13/18 21.1 10/22/18 surgery to remove zyphoid process met
Ephesians 3:20 Our God is able to do immeasurably more than we can ask or imagine!


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