Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial

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DK37
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Location: San Diego

Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial

Postby DK37 » Sat Aug 08, 2015 8:53 am

Thanks Joe for posting the Reuters article on Anti-4-1BB immunotherapies-

In general, checkpoint inhibitors (like PD-1 inhibitors) can be thought of as "releasing the brake" on the immune system; CD137 inhibitors act on the other side of the equation - they "push the gas pedal").
There is currently a trial going on specifically for CRC patients. It is a combination study of Urelumab with cetuximab at about 10 trial locations:
https://clinicaltrials.gov/ct2/show/NCT ... mab&rank=6

It is based upon this published pre-clinical study showing synergy between cetuximab & Urelumab
Full Paper: http://www.jci.org/articles/view/73014
Scientific editorial: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089450/

Interestingly, since it means to optimize the immunotherapy component of cetuximab's activity, in preclinical models they saw significant activity whether kRAS-wild type or KRAS-mutant.

I haven't seen any clinical data released yet, crossing fingers-

-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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ieowi
Posts: 202
Joined: Mon Jul 27, 2015 1:27 am

Re: Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial

Postby ieowi » Sun Aug 09, 2015 12:32 am

OUR onco. mentioned he will put my father on something similare to cetuximab along with the chemo if tumor results came back (Kras wiled I guess), as he mentioned patients who started with cetuximab and continued later, have higher survival rate than people who took it only after chemo.
I am still thinking what did he meant by similar :? will ask in his next appointment.

thanks for the post
Father 58 yo , Colon cancer IV + 4 Lymph. 7/2015
K-ras Mutant,GNAS,FBXW7,PIK3CA, MSI-low
4 cycles irinotecan+FU5
developed abdominal met + lung met...Failed
4 cycle Oxaliplatin+folfox. peri met growing...Failed
unofficial trial !!!

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DK37
Posts: 510
Joined: Tue Sep 17, 2013 8:31 am
Location: San Diego

Re: Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial

Postby DK37 » Sun Aug 09, 2015 6:41 am

ieowi wrote:I am still thinking what did he meant by similar :? will ask in his next appointment.

thanks for the post


Most likely he is referring to Vectibix. Vectibix & cetuximab are the 2 FDA-approved anti-EGFR antibody drugs for CRC.

-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
DK37 Science Posts List

ieowi
Posts: 202
Joined: Mon Jul 27, 2015 1:27 am

Re: Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial

Postby ieowi » Sun Aug 09, 2015 6:47 am

thanks for clarifying :D
Father 58 yo , Colon cancer IV + 4 Lymph. 7/2015
K-ras Mutant,GNAS,FBXW7,PIK3CA, MSI-low
4 cycles irinotecan+FU5
developed abdominal met + lung met...Failed
4 cycle Oxaliplatin+folfox. peri met growing...Failed
unofficial trial !!!

JFrog
Posts: 21
Joined: Wed Aug 26, 2015 7:55 am

Re: Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial

Postby JFrog » Fri Sep 04, 2015 12:52 pm

I wanted to add a paper to the reference for 4-1BB possible uses. I would be on the look out for a clinical trial soon for a 4-1BB and a αCTLA-4 combination.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459101/
DW dx 5/2012 Stage II @ age 45; MSS;
Emergency colostomy
5FU radiation
Resection 10/2012 and FOLFOX
Recurrence local and liver 5/2013
FOLFIRI 8 rds, Xeloda and repeat radiation
Liver res. 3/2014, repeat pelvic res. 7/2014
Liver(2) and lung recurrence(1) 9/2014, Iri w/ pan until progression then FOLFOX w/ Avastin until progression
MDA Targeted Therapy Clinical Trial 8/2015, Progressed10/15-off trial
Iri and pan. 11/2015
SBO 2/16 with successful resection 3/9/16
Clinical Trial AZD1775, 4/21/16

ieowi
Posts: 202
Joined: Mon Jul 27, 2015 1:27 am

Re: Anti-4-1BB (CD137) Immunotherapy - e.g. Urelumab CRC Trial

Postby ieowi » Sat Sep 19, 2015 6:26 pm

Any one heard anything about this cetuximab & urelumab trail ?

anyone tried it :roll:
Father 58 yo , Colon cancer IV + 4 Lymph. 7/2015
K-ras Mutant,GNAS,FBXW7,PIK3CA, MSI-low
4 cycles irinotecan+FU5
developed abdominal met + lung met...Failed
4 cycle Oxaliplatin+folfox. peri met growing...Failed
unofficial trial !!!


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