New MSS CRC Phase 1 Trial: PF-06671008 (P-cadherin targeting)

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DK37
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New MSS CRC Phase 1 Trial: PF-06671008 (P-cadherin targeting)

Postby DK37 » Mon Jan 25, 2016 6:41 pm

There is a new CRC Phase 1 trial just added to clinicaltrials .gov
NCT02659631 for an experimental drug called "PF-06671008" which targets CRC tumors with the P-cadherin cell marker.
https://clinicaltrials.gov/ct2/show/NCT ... 631&rank=1

There are specifically recruiting for CRC, including MSS. You would have to call for locations, not listed yet.

It is a Phase 1 trial so they will be starting with low dose & looking for safety in addition to efficacy.

Pfizer hasn't publicly released what exactly the drug is (as far as I can tell) but looking at its immune related exclusion criteria & their recent publication history, I think there is good chance it is a P-cadherin x CD3 bifunctional DART which is a form of immunotherapy - but that is just an educated guess at this point.

They presented a P-cadherin x CD3 bifunctional DART at a cancer conference last Spring http://cancerres.aacrjournals.org/conte ... ement/2476

If it is a DART, that strategy basically physically pulls a T-Cell right up against a tumor cell expressing the target (in this case “P-cadherin”) - once it is pulled next to it, tumor cell killing should hopefully commence. If you are familiar with the clinical trial drug “MGD007” this is the same concept just using a different cancer cell marker. Not as subtle a solution as some other immunotherapy options but... with an immunologically cold tumor like MSS-CRC, some brute force may be needed.

I'll update if it becomes confirmed what exactly PF-06671008 is -- as I said, just an educated guess at this point but it is probably their DART.

Cheers,
-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
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jortego128
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Joined: Sat Aug 15, 2015 7:47 am

Re: New MSS CRC Phase 1 Trial: PF-06671008 (P-cadherin targeting)

Postby jortego128 » Mon Jan 25, 2016 8:52 pm

DK, have you or anyone else heard how the trials are going with the MGD-007? There was that young woman and mother of some young children who had the blog (dont recall her name atm) that seemed to be responding to it, but I havent heard anything in a while. Hope she is doing OK.
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

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

Re: New MSS CRC Phase 1 Trial: PF-06671008 (P-cadherin targeting)

Postby DK37 » Tue Jan 26, 2016 12:31 pm

jortego128 wrote:DK, have you or anyone else heard how the trials are going with the MGD-007? There was that young woman and mother of some young children who had the blog (dont recall her name atm) that seemed to be responding to it, but I havent heard anything in a while. Hope she is doing OK.


Hi Jortega, she was stable on it for anumber of months, but then had progression. Dose escalation & frequency have continued to identify the maximum tolerated dose. I have not heard from people on higher doses, so I do not know if it is working or not... Maybe an update at ASCO?

-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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