French MSS-CRC Trial (PDL1 + anti-CSF1R)

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DK37
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Location: San Diego

French MSS-CRC Trial (PDL1 + anti-CSF1R)

Postby DK37 » Fri May 20, 2016 8:41 am

Yet another CSF1R trial combotherapy is opening up with PDL1. This is the 3rd or 4th trial to focuss this combo on MSS-CRC. So far it looks like a French/ European trial (so far!) for our European members or perhaps some us have French connections. The fact that 3-4 companies are independently trying this strategy on MSS-CRC, implies that they each have found activity in pre-clinical models. Here is the NCT# NCT02777710 and the link https://clinicaltrials.gov/ct2/show/NCT ... 16&rank=32

The anti-CSF1R is meant to remove immunosuppressive macrophages from the tumor.

-DK37'
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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juliej
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Re: French MSS-CRC Trial (PDL1 + anti-CSF1R)

Postby juliej » Fri May 20, 2016 3:52 pm

Thanks, Tom! I love hearing they are starting to work on MSS CRC. Surely one of these immunomodulatory combos will hit the mark! All it takes is one (even partial) success to point the way for others!

Question: Do you know anything about the new Pfizer study combining avelumab, utomilumab and OX40? That's a lot of immune manipulation! Is the point to test the limits? I know avelumab is their PD-L1 inhibitor (there are a whopping 14 avelumab abstracts at ASCO 2016!), but what are the other two?

Julie
Stage IV, liver/lung mets 8/4/2010
Xelox+Avastin 8/18/10 to 10/21/11
LAR, liver resec, HAI pump 11/11
Double lung surgery + ileo reversal 2/12
Adjuvant Xeloda 3-9/12
VATS rt. lung 12/21/12 - benign granuloma!
NED 3/17/12 to 10/2/2017, CEA<1

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

Re: French MSS-CRC Trial (PDL1 + anti-CSF1R)

Postby DK37 » Sat May 21, 2016 9:24 am

juliej wrote:Thanks, Tom! I love hearing they are starting to work on MSS CRC. Surely one of these immunomodulatory combos will hit the mark! All it takes is one (even partial) success to point the way for others!

Question: Do you know anything about the new Pfizer study combining avelumab, utomilumab and OX40? That's a lot of immune manipulation! Is the point to test the limits? I know avelumab is their PD-L1 inhibitor (there are a whopping 14 avelumab abstracts at ASCO 2016!), but what are the other two?

Julie


I first learned of this planned trial a few days ago. It is aggressive (combining the PD1 inhibitor to remove the brakes on the immune system and two drugs (targeting OX40 and 4-1BB) to push down the gas pedal to activate the immune system.) I think this is the first trial to combine 3 "modern" immuno-oncology drug mechanisms. I think one of their goals is to push the limits to see what is possible (the safety aspect of a Phase 1 trial) - but they must have animal toxicology data indicating the possibility of a safe combination + in-hand clinical safety data on 2-drug combinations giving both them & the FDA sufficient comfort to give it a try. Their efficacy goal would be to improve upon existing 2 drug combinations (some combination of: higher response rate, longer durability, achieving responses in "tougher" cancers which are more resistant to immunotherapies).

I am sure there will be more 3-drug combinations starting up, it is the next logical conclusion to try to push the technology to more cures. Safety will be the concern and closely monitored.

-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

kspoon17
Posts: 8
Joined: Mon May 23, 2016 4:46 am
Facebook Username: kilian.geoghegan

Re: French MSS-CRC Trial (PDL1 + anti-CSF1R)

Postby kspoon17 » Tue May 24, 2016 8:40 am

Have been receiving treatment in Lyon, France where they're planning this MSS Immunotherapy combo. My onc' mentioned this one yesterday saying that this may be an option for me. Will let you guys know.
12/2015: 34 yo Male Dx stage IV colon cancer with inoperable (19+) liver mets. Primary 4cm×3.5cm in transverse colon. BRAF V600E mutant - MSS
01/2016 - 05/2016: Folfirinox (3 rounds) then Folfoxiri Avastin (4 rounds) then Folfiri Avastin (3 rounds)
05/2016: Latest CT/MRI/Pet show some significant shrinkage on most lesions but one liver lesion growing (progressive disease)
CEA / CA199 : 205 / 182 pre-chemo & 295 / 1600 current

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juliej
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Joined: Thu Aug 05, 2010 12:59 pm

Re: French MSS-CRC Trial (PDL1 + anti-CSF1R)

Postby juliej » Wed May 25, 2016 5:52 pm

kspoon17 wrote:Have been receiving treatment in Lyon, France where they're planning this MSS Immunotherapy combo. My onc' mentioned this one yesterday saying that this may be an option for me. Will let you guys know.

Kilian, yes, please let us know if you get in the trial! Also, if you decide to go for the HAI pump first and have any questions about it, feel free to send me a private message. Like you, I was young when I was diagnosed with Stage IV CRC and I honestly feel like the pump saved my life. I had it implanted at Memorial Sloan Kettering in NYC.
Stage IV, liver/lung mets 8/4/2010
Xelox+Avastin 8/18/10 to 10/21/11
LAR, liver resec, HAI pump 11/11
Double lung surgery + ileo reversal 2/12
Adjuvant Xeloda 3-9/12
VATS rt. lung 12/21/12 - benign granuloma!
NED 3/17/12 to 10/2/2017, CEA<1

kspoon17
Posts: 8
Joined: Mon May 23, 2016 4:46 am
Facebook Username: kilian.geoghegan

Re: French MSS-CRC Trial (PDL1 + anti-CSF1R)

Postby kspoon17 » Thu May 26, 2016 2:50 am

juliej wrote:
kspoon17 wrote:Have been receiving treatment in Lyon, France where they're planning this MSS Immunotherapy combo. My onc' mentioned this one yesterday saying that this may be an option for me. Will let you guys know.

Kilian, yes, please let us know if you get in the trial! Also, if you decide to go for the HAI pump first and have any questions about it, feel free to send me a private message. Like you, I was young when I was diagnosed with Stage IV CRC and I honestly feel like the pump saved my life. I had it implanted at Memorial Sloan Kettering in NYC.


Thanks for the positive vibes.
Am set to meet the radiologist next week to discuss the the HAI procedure and time schedule.
May send you PM after the appointment.
12/2015: 34 yo Male Dx stage IV colon cancer with inoperable (19+) liver mets. Primary 4cm×3.5cm in transverse colon. BRAF V600E mutant - MSS
01/2016 - 05/2016: Folfirinox (3 rounds) then Folfoxiri Avastin (4 rounds) then Folfiri Avastin (3 rounds)
05/2016: Latest CT/MRI/Pet show some significant shrinkage on most lesions but one liver lesion growing (progressive disease)
CEA / CA199 : 205 / 182 pre-chemo & 295 / 1600 current


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