For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

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

For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

Postby DK37 » Mon Feb 15, 2016 10:39 pm

A new paper came out today for those of you that are KRAS-mutant. For the first time, it was shown that KRAS-mutations directly impact the immune system's response to tumors in preclinical models of KRAS-mutant CRC by means of increasing immunosuppressive “regulatory T-cells”(abreviated "Tregs") Tregs have already been shown to be a trick used by CRC tumors to suppress the immune system.

What does that mean? It means that there is a chance that using “MEK inhibitors” (which impact the KRAS pathway) as a co-therapy may help get PD-1 activity in KRAS-Mutant patients. So for KRAS-mutant patients, here is another immunotherapy trial to keep an eye on... (Cobimetinib is a MEK inhibitor) - trial sites nationwide. The trial has been going on long enough maybe they'll release some preliminary data at ASCO in June?? https://clinicaltrials.gov/ct2/show/NCT ... 896&rank=1 Today’s preclinical paper: http://cancerimmunolres.aacrjournals.or ... 1.abstract . A paper from about a year ago on synergy between MEK inhibition & PD-1 inhibition in a CRC model (CT26): http://clincancerres.aacrjournals.org/c ... 1639.short

-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

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

Re: For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

Postby Nik Colon » Mon Feb 15, 2016 11:04 pm

So, does that include MSS
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

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

Re: For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

Postby Nik Colon » Mon Feb 15, 2016 11:04 pm

Oops, dp
Last edited by Nik Colon on Mon Feb 15, 2016 11:04 pm, edited 2 times in total.
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

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

Re: For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

Postby Nik Colon » Mon Feb 15, 2016 11:04 pm

Oops, TP :shock: :roll: sorry, stupid phone!
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

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

Re: For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

Postby DK37 » Mon Feb 15, 2016 11:28 pm

Nik Colon wrote:So, does that include MSS


Hi Nik-

Based upon the clinicaltrials.gov page - the trial appears open to MSS-CRC but I haven't called to confirm-

-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

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

Re: For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

Postby Nik Colon » Mon Feb 15, 2016 11:34 pm

DK37 wrote:
Nik Colon wrote:So, does that include MSS


Hi Nik-

Based upon the clinicaltrials.gov page - the trial appears open to MSS-CRC but I haven't called to confirm-

-DK

Thanks.
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

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

Re: For KRAS-Mutant CRC: PD-1 Combination Trial with cobimetinib (MEK inhibitor)

Postby DK37 » Sat Mar 19, 2016 7:20 am

I would pay particular attention to this trial, especially if you are KRAS-mutant.

-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


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