Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

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DK37
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Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby DK37 » Mon Nov 02, 2015 9:25 am

Two more PD-(L)1 combination trials which accept MSS-CRC patients that a friend brought my attention to:

1.) A Study of the Safety, Tolerability, and Efficacy of INCB24360 Administered in Combination With Nivolumab in Select Advanced Cancers NCT02327078 https://clinicaltrials.gov/ct2/show/NCT02327078 Multiple sites nation-wide. Adds in an “IDO1 inhibitor” to remove immunosuppression signals from the tumor.

2.) MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors NCT02503774 https://www.clinicaltrials.gov/ct2/show/NCT02503774 I know of at least one more site on the east coast not listed on the clinicaltrials.gov page so call for current locations. Adds in MEDI9447 an “ant-CD73” drug to remove immunosuppression signals from the tumor.

You can see the continuing general strategy to expand PD-(L)1 inhibition to MSS-CRC tumors – by removing the local environment’s strong immunosuppression signals by a variety of theoretical mechanisms, to allow the immune system to do its job. I think this general strategy has a good chance of working – the only unknown is which specific trick (or combination of tricks) will do the job…

-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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CRguy
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby CRguy » Mon Nov 02, 2015 11:37 am

This has got to be living proof of my old Medicine Prof's saying :
" More is missed for not looking than not knowing ! "

3 CHEERS for all the dedicated researchers who keep LOOKING ... and getting further into the knowing part as well !

Thanks for this latest update. It bodes well for us all I believe.
CRguy
Caregiver x 3
Stage IV A rectal cancer/lung met
10 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

janderson
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby janderson » Mon Nov 02, 2015 3:37 pm

Thanks for the update DK. THis is encouraging. I really appreciate the time you spend posting and educating us.

Thanks again
Jeff
DX 10-05 stage IV
liver resection 12-05 Folfox1-05 to 7-06
Liver resection 8-07 Folfiri 9-07 to 3-08
Liver resection 12-11
Recurrence 2/7/2014, liver, chestwall mets, 16 rounds chemo
7/3/14, y90 radioembolization, steady shrinkage
12/8/14, cryoablation to liver and chest wall
6/1 to 6/26 SBRT radio surgery
7/2 more cryo ablation to right lung
7/16 lung infection drain tube installed
9/4 chest wall resection to remove 2 ribs

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Nik Colon
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby Nik Colon » Mon Nov 02, 2015 3:41 pm

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

ieowi
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby ieowi » Mon Nov 02, 2015 5:41 pm

Thank you DK37
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 !!!

Stanfordmom
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby Stanfordmom » Mon Nov 02, 2015 6:02 pm

yes, Thank you so much, Dk, for your research!

Sha
DX 4/2/2014 at 44, stage 4, mets liver and ovaries
Mom to 2 boys
Three surgeries, HAI pump and lots of chemo
fighting!

Ceebo
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby Ceebo » Mon Nov 02, 2015 8:44 pm

Thank you so much for this information! It gives us hope!

What is the best way to find out what other additional sites/locations are accepting patients in these trials?

Thanks, Cindie
DH 64 Stage 4 on 4/14 ; cecal tumor; 5+ nodes ; mets to liver; colon resection
5/14 FOLFOX
9/14 - Liver surgery aborted; peri mets
10/14 CT mult.1-2 mm lung mets; FOLFIRI & Avastin
1/15 CT -liver & lung mets shrinking
3/15 PET - ? New met. site colon; CEA rising
7/15 Chemo has failed; looking for clinical trial
9/29/15 started TAS-102 trial
KRAS mutant; MSS

ieowi
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby ieowi » Mon Nov 02, 2015 9:25 pm

now the only part left is waiting for some results or news to come out :evil:
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
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby DK37 » Mon Nov 02, 2015 9:51 pm

Ceebo wrote:Thank you so much for this information! It gives us hope!

What is the best way to find out what other additional sites/locations are accepting patients in these trials?

Thanks, Cindie


Anyone interested in these trials... in both cases if you hit the hyperlink in the original post, scroll down and you'll find a toll-free number to call for information. That phone # person will know the current status of trial locations - you just have to give them the "NCT#" which I also listed in the post.

As a reminder - there is no human CRC data released yet on these trials, so consider that and the possibility of potential blockage from future PD-1 trials as you strategize with your MD if and when to enter one of these trials.

-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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DK37
Posts: 510
Joined: Tue Sep 17, 2013 8:31 am
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Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby DK37 » Mon Nov 02, 2015 9:52 pm

ieowi wrote:now the only part left is waiting for some results or news to come out :evil:


The waiting part is very tough.......................

-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: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby ieowi » Mon Nov 02, 2015 9:55 pm

DK37 wrote:
ieowi wrote:now the only part left is waiting for some results or news to come out :evil:


The waiting part is very tough.......................

-DK


Very Very Very Tough
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 !!!

dudette
Posts: 106
Joined: Sat Oct 17, 2015 10:04 am

Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby dudette » Mon Nov 02, 2015 11:22 pm

Thank you for providing valuable information!

Although I am in Europe I collect as much information as possible from anywhere. You never know when it might become relevant.
Temi
Dx 03/2015 @ age 41 - CC stage IV - pT3 N2b (14/29) cM1 (hep) L1 V1 Pn1 R1
Wild K-RAS, N-RAS, BRAF / MSS
unresectable mets liver 60% + lungs
Surgery
04/15 - sigmoid resect.
07/16 - hysterectomy (ovaries)
Chemo
05-06/15 - 4 x Folfirinox
12/15 - 02/16 4 x Xeliri + Avastin
03-05/16 9 x Xeloda
09-12/16 Folfiri + Cetuximab
01/2017 - metronomic chemo + methadone
July 20, 2107 - Temi has passed away.

jortego128
Posts: 272
Joined: Sat Aug 15, 2015 7:47 am

Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby jortego128 » Sun Nov 15, 2015 7:32 pm

**Edit: These results are not from the Opdivo combo, but from the Keytruda combo-- that may explain the absence of CRC patients.

Incite posted some prelim results of the IDO1 (Epacadostat)+ Opdivo trial being held in Birmingham, AL. This release shows results of several solid tumor cancers, but CRC was not included in the release, despite the trial stating it was accepting CRC patients. I wonder if CRC wasnt shown due to lack of patients in the trial or lack of response...

ieowi, if you are having trouble finding a trial and need one now, perhaps you could call and inquire if there are indeed any CRC patients and if any MSI-low or MSS patients have responded.

http://investor.incyte.com/phoenix.zhtm ... ID=2105804

http://www.immunotherapyofcancer.org/co ... -S2-O7.pdf
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

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

Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby ieowi » Sun Nov 15, 2015 8:25 pm

jortego128 wrote:**Edit: These results are not from the Opdivo combo, but from the Keytruda combo-- that may explain the absence of CRC patients.

Incite posted some prelim results of the IDO1 (Epacadostat)+ Opdivo trial being held in Birmingham, AL. This release shows results of several solid tumor cancers, but CRC was not included in the release, despite the trial stating it was accepting CRC patients. I wonder if CRC wasnt shown due to lack of patients in the trial or lack of response...

ieowi, if you are having trouble finding a trial and need one now, perhaps you could call and inquire if there are indeed any CRC patients and if any MSI-low or MSS patients have responded.

http://investor.incyte.com/phoenix.zhtm ... ID=2105804

http://www.immunotherapyofcancer.org/co ... -S2-O7.pdf


Jortego128,
thank you, I have already seen these results the only issue here is this trial doesn't show if IDO1 did anything for the patients as they combine both of them, so if you combine water with keyrtuda you may end up with these results too.
DK37 may have more to say about this.

furthermore I have contacted San Antonio ( one of the locations doing the combination Keyrtuda+IDO1 ) and this is what they said """" IN THEORY IT IS POSSIBLE TO WORK ON MSS, MSI-LOW BUTTTTTTTTTTTT IN MY OPINION NOT LIKELY"""""
that's was there respond. so we left this behind us I will take there word for it we can't risk anything considering Dad condition. They said though you are welcomed to try but in feb. as they already have one patient and two in the waiting list.

the CD73 will start soon I called duke university NC, it would be escalation dose for a couple of month for CD73 then they would combine them both, I don't think we have that much of time.
so I am waiting to see if MSKCC have something else to offer beside what they first suggested, which wasn't very realistic. and tomorrow we will see MDA to see what they have.
Last edited by ieowi on Sun Nov 15, 2015 9:22 pm, edited 1 time in total.
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 !!!

Ceebo
Posts: 132
Joined: Sat Feb 14, 2015 9:15 am
Location: Southwest Michigan

Re: Two more PD-(L)1 Combo Trials Hoped to Make MSS-CRC Tumors "Hot" Towards the Immune System (IDO1 & CD73)

Postby Ceebo » Sun Nov 15, 2015 8:34 pm

DK, Thanks for the information on how to find out more about other trial locations and also thanks for the words of wisdom and caution! --Cindie
DH 64 Stage 4 on 4/14 ; cecal tumor; 5+ nodes ; mets to liver; colon resection
5/14 FOLFOX
9/14 - Liver surgery aborted; peri mets
10/14 CT mult.1-2 mm lung mets; FOLFIRI & Avastin
1/15 CT -liver & lung mets shrinking
3/15 PET - ? New met. site colon; CEA rising
7/15 Chemo has failed; looking for clinical trial
9/29/15 started TAS-102 trial
KRAS mutant; MSS


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