New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda

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

New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda

Postby DK37 » Tue May 03, 2016 12:34 pm

Another new MSS-CRC immunotherapy trial-

It combines Erbitux (cetuximab) with Keytruda (pembro) as PD1 inhibitor. It is at the Roswell Park Cancer Institute in Buffalo, New York.

You need to be KRAS and NRAS wild-type and not have taken an EGFR inhibitor previously -- but a previous PD1 inhibitor looks OK. NCT02713373

https://clinicaltrials.gov/ct2/show/NCT ... 373&rank=1

-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://colorectalmsstrials.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

sdino
Posts: 20
Joined: Tue Mar 28, 2017 5:32 pm

Re: New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda

Postby sdino » Fri May 19, 2017 8:18 am

Hi DK37 - hope things are going well for you. Just heard about this trial NCT02713373. We are currently at Roswell Park Inst. with Dr Boland as our Oncologist (clinical trial admin),. As you can see below in my Signature, my wife is KRAS Mut. Would that exclude her from this trial ? Must you be Kras-Wild type ?

We have had some good results (shrinkage lung mets and colon tumor) with standard Chemo. As a matter of fact she is on a 2 month chemo break, so I not going to call our Onc. and take a break from all this stuff until we meet with him in July. thx... sdino
Caregiver for Wife 52 yrs old
DX: 11/16-CC sigmoid colon 3 cm, Lung Bio-Adenocarcinoma Stg IV
Mets: 1.2 cm now 7 mm lung w/14 other nodules less than 6 mm.
3 lymph nodes
MSS, KRAS-mut G12D; TP53;
Chemo: Complete 12 rounds Folfox/Avastin + Oxi 11/16 to 5/17
CT Scans: 11/16; 1/17 lung mets/colon shrinkage; 3/17 lung mets no change, shrinkage lymph/colon tumor, 5/17 colon & lung met shrinkage
CEA: 16 - 11/16; 4 – 12/16; 0.7 – 1/17; 0.5 – 2/17; 0.6 - 5/17

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Maia
Posts: 2279
Joined: Fri Aug 24, 2012 8:00 am

Re: New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda

Postby Maia » Mon May 22, 2017 2:06 pm

Sdino, yes, being KRAS mutant is exclusion criterion for this trial. But there are many trials for which she qualify!

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GrouseMan
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Joined: Mon Aug 12, 2013 12:30 pm
Location: SE Michigan USA

Re: New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda

Postby GrouseMan » Mon May 22, 2017 11:10 pm

And the reason they excluded people that have previously used an EGFr inhibitor is because the tumors build up a tolerance to EGFr inhibitors as my wide did. (in combination with Irinotecan and Avastin). However as they have found many times a tumor will again become sensitive to EGFr treatment after a period of time without being treated with an EGFr inhibitor. Apparently the tumors would rather revert back to the EGFr pathway than the alternative ERbb2, 3 and 4 pathways it uses to get around the EGFr pathway blockade. I wish I could find that publication again.

Good luck guys.... Wish I knew about this one and that it were local to us before my wife did the Irrinotecan, Erbitux, Avastin trial.

GrouseMan
DW 53 dx Jun 13
CT mets Liver Spleen lung. IVb CEA~110
Jul13 Sig Resct
8/13 FolFox + Avastin 12Tx mild sfx
Ongoing 5-FU Avastin every 3 wks.
CEA: 9/23/13 53 10/21/13 22 12/2/13 8 1/13/14 3.7 8/12/14 2.3 7/2/15 4.0 8/21/15 5.9
7/7/14 CT Can't see the spleen Mets Stable until... CEA up
8/16/15 CT new abdominal spots. Now Iri, 5-FU, Avastin every other week.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen

Achilles Torn
Posts: 48
Joined: Fri Dec 16, 2016 2:41 pm

Re: New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda

Postby Achilles Torn » Wed May 24, 2017 12:37 am

Grouseman. Sorry to hear about your wife's recent blockage. I hope things are getting better.

This is an interesting trial to me as well. You mention ERRB pathways to get around EGFR inhibition. That interests me as I have ERRB4 mutation. Did the paper you read indicate having such a mutation would make EGFR inhibitors ineffective so maybe not the trial for me ?

Cheers
AT
40 yo Male. DX By Surgeon Dec. 8 2016
Sigmoid Colectomy Dec. 9 2016
Pathology T3N2b?MX 19 of 24 Nodes Positive.
peri colonic tumor deposits 8cm from Tumor. Perineural invasion positive.
PET scan shows Para-Aortic and Iliac Lymph node spread.
Moderately differentiated. MSS. KRAS/BRAF Wild
FOLFOX Commenced Jan 9/2017 - Avastin(Bev) added after 1st round

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GrouseMan
Posts: 713
Joined: Mon Aug 12, 2013 12:30 pm
Location: SE Michigan USA

Re: New MSS-CRC Immunotherapy Trial: Erbitux+Keytruda

Postby GrouseMan » Wed May 24, 2017 1:22 pm

Achilles Torn wrote:Grouseman. Sorry to hear about your wife's recent blockage. I hope things are getting better.

This is an interesting trial to me as well. You mention ERRB pathways to get around EGFR inhibition. That interests me as I have ERRB4 mutation. Did the paper you read indicate having such a mutation would make EGFR inhibitors ineffective so maybe not the trial for me ?

Cheers
AT


Well - I went looking for the paper again and couldn't find it in any of my saved web pages about EGFr inhibitors which is one of the anticancer drug candidates I worked on (dacomitinib) in some of its early synthetic stages. It will likely depend on the ERBB4 mutation. The particular EGFr inhibitor in this study is Erbitux (Cetuximab) a Monoclonal antibody, that binds to the surface EGFr protein - I am not sure of the specific binding site. But generally its not usually the ATP binding pocket like small molecule EGFr inhibitors bind. I don't know to what extent the antibody binds to other ERbb family members. Probably non at all.

The mutation you have they may not know if its driving your cancer or not. But I suspect that if it is the Erbitux will not bind to it anyway. You would need a different EGFr inhibitor that binds both EGFr and ERBB4. Wouldn't hurt if it also bound to the others Erbb2, 3 as well. Dacomitinib does bind EGFr, Erbb2 and Erbb4.

Here is a link about Erbb4: https://en.wikipedia.org/wiki/ERBB4

another about Dacomitinib: http://pubs.acs.org/doi/abs/10.1021/bk-2016-1239.ch008

It never hurt to ask the Clinical Trial manager if you qualify or not.

If I could create a clinical trial similar to this I would elect to use Dacomitinib + Keytruda instead.

GrouseMan
DW 53 dx Jun 13
CT mets Liver Spleen lung. IVb CEA~110
Jul13 Sig Resct
8/13 FolFox + Avastin 12Tx mild sfx
Ongoing 5-FU Avastin every 3 wks.
CEA: 9/23/13 53 10/21/13 22 12/2/13 8 1/13/14 3.7 8/12/14 2.3 7/2/15 4.0 8/21/15 5.9
7/7/14 CT Can't see the spleen Mets Stable until... CEA up
8/16/15 CT new abdominal spots. Now Iri, 5-FU, Avastin every other week.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen


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