New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

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DK37
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New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby DK37 » Fri Jan 15, 2016 12:57 pm

A new immunotherapy trial has been announced open to BOTH MSI & non-MSI (MSS) CRC. Also of note, it does not exclude for prior PD-1 use.

It is a combo therapy with a drug called "CPI-444" which targets the "adenosine-A2A receptor" which is believed to potentially cause immunosuppression in "cold tumors". This will be the first trial testing this strategy (so no human data yet) - but it is a strategy where multiple companies will probably be testing in 2016 based upon animal model data.

Adenosine-A2A receptor drugs have been tested for other uses before and as a drug class, they have had a good safety record although I do not know if this exact drug has been tested before.

They're betting big on this trial - as a Phase 1 trial, they are shooting for 544 patients across 8 tumor types. Locations have not been announced yet.

EDITS TO ORIGINAL POST:
Thank you to JFrog for pointing out (actually in a post yesterday I missed!) that this trial is RANDOMIZED so at least to start, 3/4 of patients get the experimental drug alone - 1/4 get it as a combo with a PD-1 inhibitor. There are a lot of pre-clinical papers on this target, although to be honest I'm a bit surprised they are betting so big on single agent - I'm curious (but don't know) their internal data which prompted them to set up the trial in this way.

EDITS TO ORIGINAL POST #2:
I did some more digging on CPI-444 just because its Phase 1 clinical plan was SO ambitious (4 dose cohorts, 8 tumor types as a Phase 1), I wanted to figure out what the heck their story was...

Here is their SEC filing from last week: https://www.sec.gov/Archives/edgar/data ... 67zs-1.htm

The molecule was previously found safe in healthy volunteers for (unfortunately failed) Parkinson's Disease development, reducing safety risk. Although it is VERY important to point out that it is MUCH easier to successfully treat cancer in mice than in humans... (if we were mice instead of people we wouldn't be in Colon Talk right now!) they have seen significant activity in some CRC mouse models even as a single agent (even better with PD1 combo) - which explains why they are trying both single agent & PD-1 combo in the Phase 1 clinical trial.

For anyone who wants to get far down into the data p81-p90 of the SEC link = their preclinical CRC mouse data & clinical development plan.

Once again, I want to strongly point out that cancer is much easier to treat in mice than in humans so there is far from a guarantee of human activity - but I think taken together: the safety aspect, plus their mouse model data (plus heavy competitive pressure) explains why they are planning such an abnormally big Phase 1 trial.

https://clinicaltrials.gov/ct2/show/NCT ... 822&rank=1

-DK
Last edited by DK37 on Sun Jan 17, 2016 2:34 pm, edited 2 times 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
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JDinNC
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Location: Murphy, N.C.

Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby JDinNC » Fri Jan 15, 2016 1:34 pm

I don't want to sound naive but are these trials open to people that are NED at the moment. Being stage 4 colon and stage 2 melanoma..I was wondering if these trials would help me. I feel helpless just sitting here waiting for the next recurrence .

Jan
61 y/o female @ DX...........
T3N0M1
6/13 DX- stage 4
Sigmoid colon cancer.
One met to lung
7/13 colon resection
8/13 lung resection
7/17 four years....NED
8/18 five years....NED
MELANOMA
63 y/o @ DX
6/15 stage 2a
7/15 surgery on arm
7/15 NED
4/16 recurrance
5/16 remove metastasis from back
5/16. Started immunotherapy
8/16 discontinue treatment
7/18...PET scan...NED

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DK37
Posts: 510
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Location: San Diego

Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby DK37 » Fri Jan 15, 2016 1:55 pm

EDITS TO ORIGINAL POST:
Thank you to JFrog for pointing out (actually in a post yesterday I missed!) that this trial is RANDOMIZED so at least to start, 3/4 of patients get the experimental drug alone - 1/4 get it as a combo with a PD-1 inhibitor. There are a lot of pre-clinical papers on this target, although to be honest I'm a bit surprised they are betting so big on single agent - I'm curious (but don't know) their internal data which prompted them to set up the trial in this way.

JDinNC
Unfortunately almost all trials (and I presume this one too - but it will be in their listed inclusion/exclusion criteria) require a "measurable lesion" for trial admittance, to allow them to measure success/failure of activity in a quantitative sort of way. Sorry......


-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

KElizabeth
Posts: 400
Joined: Sat Oct 31, 2015 12:41 pm
Facebook Username: KElizabeth
Location: Omaha

Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby KElizabeth » Fri Jan 15, 2016 2:01 pm

I'm definitely interested in exploring this when more information is available. Let's cross our fingers that something is available in the Midwest or someplace inexpensive to fly into.
Female age 39- ,2 teens.
Colon Cancer - DX March 2013
Age 34 at DX - Stage III B
Resection surgery -May 2013
FOLFOX - June, 2013 to Sept, 2013
5FU plus leukavorin Sept, 2013 to Dec, 2013
METs liver and lungs discovered Sept, 2015
KRAS - MSS
FOLFIRI plus Avastin - Sept, 2015 - July 2017
Durvalumab and Cediranib Sept 2017 Dec 17
FOLFOX with desensitization protocol - current

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DK37
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Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby DK37 » Sun Jan 17, 2016 2:35 pm

Please see my edits #2 to the original post with additional information.

-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

Steph20021
Posts: 533
Joined: Sat Dec 27, 2014 4:58 pm
Location: Ontario, Canada

Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby Steph20021 » Mon Jan 18, 2016 12:23 am

When will we know where it's available? Could it also be open in Canada?
DX 1/31/14 @ 33- SPS-T4a(invades visceral peri), N2a(6/106 LN), M1a(ovary) (Stage 4a) MSS; BRAF V600E mutation
2/1/14-subtotal col, lost R ovary, temp ileo
3/14-9/14- folfox; sepsis
11/14-CT/PET: L ovary met, pelvic met, (?)ghost liver met(?)
12/14-folfiri -13 rds kept me stable from 3/15-6/15
8/15-HIPEC, hysterectomy et al, 2nd temp ileo, NED?
09/15- cea 0.9
05/16- recurrence in abdo wall and lymph nodes
Jan/17- pulmonary embolism
Feb/17- 1 wk radiation to abdo wall
Aug/16- on folfiri
Jan/18-folfox

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

Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby DK37 » Mon Jan 18, 2016 10:43 am

Steph20021 wrote:When will we know where it's available? Could it also be open in Canada?


They should update the website with locations relatively soon but you can always contact them at the contact info given to ask them for the latest info. One thing I am curious about is that since it appears they are accepting both MSI-high and MSS-CRC patients (since they don't specific MSI-high only in their criteria), I am curious the number of slots they will allocate to each subtype. I don't know the answer to that question.

-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

Steph20021
Posts: 533
Joined: Sat Dec 27, 2014 4:58 pm
Location: Ontario, Canada

Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby Steph20021 » Mon Jan 18, 2016 12:59 pm

DK37 wrote:
Steph20021 wrote:When will we know where it's available? Could it also be open in Canada?


They should update the website with locations relatively soon but you can always contact them at the contact info given to ask them for the latest info. One thing I am curious about is that since it appears they are accepting both MSI-high and MSS-CRC patients (since they don't specific MSI-high only in their criteria), I am curious the number of slots they will allocate to each subtype. I don't know the answer to that question.

-DK

Hey DK! I heard back from contact lady Danielle very very fast and she said in Canada likely in Feb! Wahoo!
DX 1/31/14 @ 33- SPS-T4a(invades visceral peri), N2a(6/106 LN), M1a(ovary) (Stage 4a) MSS; BRAF V600E mutation
2/1/14-subtotal col, lost R ovary, temp ileo
3/14-9/14- folfox; sepsis
11/14-CT/PET: L ovary met, pelvic met, (?)ghost liver met(?)
12/14-folfiri -13 rds kept me stable from 3/15-6/15
8/15-HIPEC, hysterectomy et al, 2nd temp ileo, NED?
09/15- cea 0.9
05/16- recurrence in abdo wall and lymph nodes
Jan/17- pulmonary embolism
Feb/17- 1 wk radiation to abdo wall
Aug/16- on folfiri
Jan/18-folfox

plastikos
Posts: 301
Joined: Wed Jan 14, 2015 6:09 am

Re: New Immunotherapy Combo Trial Open to both MSI-high & MSS CRC (CPI-444; adenosine-A2A combo)

Postby plastikos » Mon Jan 18, 2016 10:29 pm

JDinNC wrote:I don't want to sound naive but are these trials open to people that are NED at the moment. Being stage 4 colon and stage 2 melanoma..I was wondering if these trials would help me. I feel helpless just sitting here waiting for the next recurrence .

Jan

I know exactly how you feel. Nevertheless this is great news especially for MSS patients.
Diagnosed St. IV Colon CA @ 37, male, Kras wild type, MSI-high (2014)
11/2014 Right Hemicolectomy + Liver Resection
12/2014 - 6/2015 FOLFOX + Cetuximab
10/2015 - Recurrence liver
Liver resection 10/2015
FOLFIRI 11/2015 - 5/2016
Recurrence liver, nodes 11/2016
Pembrolizumab 12/2016 -> pseudoprogression (?), biliary obstruction -> biliary stenting
Chemo 4x: most mets inactive and smaller on PET-CT
March 2017 - Back on Pembrolizumab
Sept 2017 - SIRT


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