New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

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DK37
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Location: San Diego

New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

Postby DK37 » Mon Aug 31, 2015 2:34 pm

Hi Everyone,

I’m not sure if these have been mentioned before. I noticed 2 new recently opened PD-1 inhibitor immunotherapy combination clinical trials that either accept all types of CRC or are specifically intended for MSS-CRC (note I said MSS!).

As I have mentioned before, scientists hope that PD-1/PD-L1 inhibitors can become a backbone therapy for many cancers (including CRC) in the future with additional drugs added to them as a combination cocktail, to hopefully make them active against MSS-CRC (and also to hopefully improve response rate and/or durability of response in MSI-CRC).

Also, I wanted to note that as a strategic choice, many combination trials with PD-1/PD-L1 inhibitors EXCLUDE patients who have previously taken them – so choosing to sign up for a PD-1/PD-L1 inhibitor trial should “strategically” not be taken lightly – you might be precluded from some future PD-1/PD-L1 combination trials if future trials are needed. These trials are all highly experimental, since the “tricks” needed to get PD-1/PD-L1 activity in MSS-CRC have not been proven yet in clinical trials, although there are indications various combination therapies could work based upon pre-clinical animal models.

Here are the 2 trials:

1.) NCT02512172. New Phase 1. Johns Hopkins. Combination of: Two epigenetic modifying drugs + anti-PD1 MK-3475 (pembrolizumab). Intended to try to make MSS-CRC tumors more easily seen by the immune system. https://clinicaltrials.gov/ct2/show/NCT ... 15&rank=14
2.) NCT02526017. New Phase 1. So far in San Antonio, they want to accrue hundreds of patients so I believe will be expanding to multiple sites. Combination of anti-CSF1R antibody + anti-PD1 Nivolumab. Intended to try to make CRC tumors less immunosuppressive. https://clinicaltrials.gov/ct2/show/NCT ... 15&rank=40

Cheers,
-DK
Last edited by DK37 on Mon Aug 31, 2015 2:41 pm, edited 1 time in total.
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

Carolinagirl
Posts: 73
Joined: Mon Dec 17, 2012 7:39 pm

Re: New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

Postby Carolinagirl » Mon Aug 31, 2015 2:37 pm

This information is so incredibly helpful! Thank you!!
12/12 colon resect. Stage IIIb 35 yo
KRAS mutant, MSS
1/13 Folfox
11/13 local recurrence pelvis
12/13 Folfiri + Zaltrap x 4
2/14 xeloda + rad x 28
5/14 lung mets/resection
6/14 Irinotecan/5FU
9/14 Posterior Pelvic Exenteration
10/14 Xeloda/Avastin
11/15 peritoneal mets
FOLIFIRI + zaltrap

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

Re: New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

Postby JFrog » Mon Aug 31, 2015 3:04 pm

Thank you so much, great info. Our docs at MDA have said there are more combo immunotherapy trials opening very soon for MSS.
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

gator.girl
Posts: 37
Joined: Thu Sep 05, 2013 1:05 pm

Re: New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

Postby gator.girl » Mon Aug 31, 2015 3:22 pm

Thanks DK! This is exciting for MSS! So stressful though to have to play this strategically.... Yikes - when do you know to jump in?

Rachel
Dx 8/13 @ 40
Stage IV - innumerable mets to liver
12 rounds of Folfox + Avastin
8 months on maintenance
11/14 Y90 to right side of liver
01/15 Gallbladder removal and colon resection
02/15 Mets to lungs
Now on Folfiri

jortego128
Posts: 286
Joined: Sat Aug 15, 2015 7:47 am

Re: New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

Postby jortego128 » Mon Aug 31, 2015 3:28 pm

Thanks for the update Tom! These trials cant come fast enough! :D
DM 57 yrs old dx 6/8/15 T:4a N:1b M:1
KRAS G12D and TP53 C242fs mutations
Poorly Differentiated, Prominent Signet Ring Component(~50%)
Microsatellite Stable, 3 of (13)lymph nodes positive
15 Liver mets, largest 3.2 cm
Prim. Resection, Right Hemicolectomy 6/21/15
Start Chemo 7/20/15
2 rounds FOLFOX, 1 round FOLFOX +Avastin
CT 8/28/15, met growth, largest 4.5cm
4 rounds FOLFOX+Avastin
CT 11/06/15 mets stable, lungs clear
Begin FOLFIRI+Avastin 11/17/15, Stop chemo 1/26/16
Entered Paradise 3/11/2016

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

Re: New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

Postby DK37 » Mon Aug 31, 2015 5:53 pm

gator.girl wrote:Thanks DK! This is exciting for MSS! So stressful though to have to play this strategically.... Yikes - when do you know to jump in?

Rachel


That's the gazillion dollar strategy question Rachel... I wish I had a good answer... :? Because of potential later trial exclusion, personally I would be a little nervous doing a PD-1 trial until either 1.) There was word filtering e.g. here on Colon Talk that results were good from a particular combination or 2.) I was starting to run out of other options. BUT - I fully and openly say that this is just my personal opinion - there is certainly no right or wrong strategic answers, we're all (including me!) just guessing what path to follow without actual data in hand... The original & current MSI-CRC folks on the PD-1 trial bravely took a big risk (even with the above strategic consequences) and many of them have seen a response! Now it is MSS-CRC's turn to find our active immunotherapy...

-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: New PD-1 Inhibitor Combo Studies for CRC (All or MSS Specific)

Postby ieowi » Tue Sep 01, 2015 2:33 am

DK37,

I cant thank you enough for sharing all these information and updates ! thank youuuuuuu I always look to read your posts here.
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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