(Good) News on anti PD-L1 MPDL3280A / Immunotherapy

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Maia
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Maia » Fri Feb 07, 2014 9:06 pm

It sounds like sci-fi -Merck and Pfizer collaborating! :shock:
I see most of the links you listed (plus the last clinical trial I mentioned, MEHD7945A + cobimetinib) like examples of a trend, in all these developments: a drug that targets the PD-1/PD-L1 pathways (an actual immunotherapy, if you want) *plus* some kind of other monoclonal antibody/ small molecule inhibitor. Am I right... even the big pharma companies are going for combinations of drugs, realizing the need of targeting, *simultaneously*, different pathways? It's what most of the CAM approaches have been trying to do since years ago.
GrouseMan, thank you for those links --I know something about Roche/Genentech candidate, and about Merck's (lambrolizumab; in fact, I was reading this, published today! : ), because resulted so good against melanoma, but about the others... little to nothing. Oy, you'll make me read more. :D Thank you, you're great!
*************
About the strategy of targeting the PD-1/PD-L1 pathway against cancer, I have bookmarked what it looks like a very, very good article from OncLive. I've only skipped through it (it's one week old), so far; sharing it here:

The Role of Anti-PD-L1 Immunotherapy in Cancer

Published Online: Wednesday, January 29, 2014
It's 8 pages long, it's has a good resume about the agents in development (see tables in pages 4, 5 and 7, if you have little time) and a good, quite accessible explanation about the functioning of our dear immune system. :)

(sorry about all the English mistakes... it's too late to correct too much : )

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CRguy
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby CRguy » Fri Feb 07, 2014 10:25 pm

Maia wrote:It sounds like sci-fi -Merck and Pfizer collaborating! :shock:

"...when worlds collide ...." :shock:
CRguy
Caregiver x 4
Stage IV A rectal cancer/lung met
12 Year survivor
my life is an ongoing totally randomized UNcontrolled experiment with N=1 !
Review of my Journey so far

Asterix
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Asterix » Mon Feb 10, 2014 6:22 pm

Well, this is fun. I emailed the roche contact last week and haven't heard anything. I've tried ringing Peter Mac in Melbourne and got no where. I finally rang roche in Australia and they are contacting their trials team and may get me some information, but it might take a few days. Hopefully I'll get the information I need.
Stage IVb age 37 Nov11
FOLFOX+Avastin, Xeloda+Avastin
1 year NED
regorafenib Oct13-Feb14
lymph node, lung, spine, rib and liver mets
GNAQ Q209P mutation > Mekinist Jul14
Radiation bone mets Aug14
Pain>hospital Oct14
FOLFIRI Nov14 >
Home Xmas 14

Asterix
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Asterix » Wed Feb 12, 2014 6:44 pm

Ok, my onc is on board any agrees that looking at trials now while I'm still "healthy" is the best option. He contacted his Roche rep while I was there to find out where the studies are exactly. Meanwhile I called Roche Australia and they have gotten back to me with the trial information. It at Austin Hospital, Peter Mac and Royal Melbourne. I have names and phone numbers but I won't put them up publicly, but anyone in Australia who wants them can PM them to me. I haven't called them myself, I've given them to my onc so he can follow up.

My CEA is still going up, but slower to it seems the regorafenib is only doing a partial job on my cancer. I'm due for a scan but we are going to wait until we get the trial information so we don't end up doing extra scans if the trial wants specific scans.

Thanks Maia for posting this. I doubt I would have found it myself.

Here's something I found, I haven't read them yet but they look interesting.
http://gicasym.org/sites/gicasym.org/fi ... 000060.pdf
Stage IVb age 37 Nov11
FOLFOX+Avastin, Xeloda+Avastin
1 year NED
regorafenib Oct13-Feb14
lymph node, lung, spine, rib and liver mets
GNAQ Q209P mutation > Mekinist Jul14
Radiation bone mets Aug14
Pain>hospital Oct14
FOLFIRI Nov14 >
Home Xmas 14

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Maia
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Maia » Wed Feb 12, 2014 7:23 pm

Asterix wrote:Ok, my onc is on board any agrees that looking at trials now while I'm still "healthy" is the best option. He contacted his Roche rep while I was there to find out where the studies are exactly. Meanwhile I called Roche Australia and they have gotten back to me with the trial information.


Ahhhhhhhhh..! Asterix, I'm so, so happy for you, in a way you couldn't believe! I'm giving your onc a big hug in my heart. So many patients have to go on their own to explore this route -and many others would have wanted to try, but never do it, only because of the lack of support --not because a trial wasn't right for them.
I'm thanking *you* for posting this-you have lightened my night, my week. Thank you, so much!! :)
Congrats, my Southern Hemisphere fellow -a summer hug from Argentina.

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Maia
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Maia » Sat Feb 15, 2014 8:57 pm

Little update: on February 10th, they added 4 more locations (still 'not yet recruiting') -they were 38 locations, they are 42 now.
http://clinicaltrials.gov/ct2/show/study/NCT01988896

Asterix
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Asterix » Sat Feb 22, 2014 12:43 am

Well, my onc contacted the other doctors and the trial won't be starting in Melbourne until late this year. I wonder if Roche would fly me to New York and back every 3 weeks :)
Stage IVb age 37 Nov11
FOLFOX+Avastin, Xeloda+Avastin
1 year NED
regorafenib Oct13-Feb14
lymph node, lung, spine, rib and liver mets
GNAQ Q209P mutation > Mekinist Jul14
Radiation bone mets Aug14
Pain>hospital Oct14
FOLFIRI Nov14 >
Home Xmas 14

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Maia
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Maia » Sat Mar 01, 2014 10:45 am

Asterix, you may feel a little disappointed, but I think it's great you've been so proactive. Now you know the trial will be there *if* you need it, you know your onc is on the same page... all that sounds good. Hope the regorafenib keep working for you, at the lower dose, so you don't even have to touch Folfiri. :)

**************

UPDATE March 1st: To the already 'recruiting' locations (New York, Tennessee and North Caroline), these have been added:

Locations changed from 'not yet recruiting' to 'Recruiting':

Denver, Colorado, United States, 80220

Tyler, Texas, United States, 75702

Vancouver, Washington, United States, 98684

**********

pete43lost_at_sea
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby pete43lost_at_sea » Mon Mar 03, 2014 8:57 pm

This is a fantastic post.
Just wanted to add I had anti pd1 dc vaccine 7 days ago.
Cea has crashed from 204 to 29.
Details on blog.
Doing lots of stuff and some of its working exceptionally well.

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GrouseMan
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby GrouseMan » Fri Mar 07, 2014 12:08 pm

I have been away on a business trip so couldn't keep up with all my usual haunts. I read a blog by another medicinal chemist which often talks about he pharmaceutical industry in general, the discovery process, specific drugs and companies some times.

So - have a look at this discussion and the links imbedded in the text.

http://pipeline.corante.com/archives/20 ... p#comments

Regards,

GrouseMan
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017

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Maia
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Maia » Fri Mar 07, 2014 12:25 pm

Nivolumab (BMS-936558), the Bristol-Mayers anti PD-L1, is so promising now also for CRC. I was going to start other thread for that, days ago, now you got me motivated, GrouseMan : )

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Maia
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Maia » Sat Mar 22, 2014 1:38 pm

Update March 22 2014:
This trial
(A Study of the Safety and Pharmacology of MPDL3280A Given With Cobimetinib in Patients With Locally Advanced or Metastatic Cancer
http://clinicaltrials.gov/ct2/show/study/NCT01988896)
is now recruiting at

Denver, Colorado
New York, New York,
Chapel Hill, North Carolina
Nashville, Tennessee
Arlington, Texas
Tyler, Texas
Seattle, Washington,
Vancouver, Washington

http://clinicaltrials.gov/ct2/show/stud ... ocs=Y#locn

dianne052506
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby dianne052506 » Sat Mar 22, 2014 2:07 pm

Maia,
I can't find much on this new drug, cobimetinib. I wonder what the possible side effects could be. MPDL3280-A wasn't bad, but I wonder if the kidney issues will totally resolve or if they would keep me out of something new.
The trial info does not say that you are excluded if you have had other immune therapy. I think I'll call Chapel Hill Monday and see. (We are going to Chapel Hill next weekend for my daughter to look at the university there!)

Thank you for the info. I've been so down, I've stopped looking. Hugs to you.
Dianne
May 06 Stage IV CC: liver,ovarian mets
Oct 07 inoperable lung mets
Feb 08 - Apr'12 chemo
allergic to oxaliplatin, irinotecan
Aug '12-Feb'14 Genentech PD-L1/Avastin trial
Mar '14 -radiation to largest lung nodule
still recovering; looking at trials again

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singingholly
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby singingholly » Sat Mar 22, 2014 2:19 pm

Thank you so much Maia, you're an angel.
Dec2011 sigm IIIst res T3N1(2/18)M0 Xelox
Oct2012 5liv.mets Dec 2012 liv.res
Jan2013 1liv.met Folfiri+avastin
Jul2013 liv.res Folfiri+/av
Feb2014 10+2lu.mets & 1abd node Folfoxiri+SBRT
Sep2014 Res rx l. BUT spot on diaph:SBRT
Dec2014 3+6lu.mets.Immuno

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Maia
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Re: (Good) News on anti PD-L1 MPDL3280A / Immunotherapy

Postby Maia » Sat Mar 22, 2014 2:36 pm

dianne052506 wrote:Maia,
I can't find much on this new drug, cobimetinib. I wonder what the possible side effects could be.


I posted what I found in some previous posts in this thread. Cobimetinib, is a MEK inhibitor. It's oral (given by mouth). It's not something totally new: it has been around for a while, on clinical trials, combined with other agents, and with them has shown good results for melanoma, which is not surprising for immunotherapies. Difficult to say which side effects come from cobimetinib and which ones for other agent, but some articles here: http://www.ascopost.com/issues/december ... oming.aspx http://cancerdiscovery.aacrjournals.org ... 8.abstract http://informahealthcare.com/doi/abs/10 ... 014.892578
In general, immunotherapies have *transient* side effects (that can be strong, though). But cobimetinib is not the immunotherapeutic agent in the combo (MPDL3280A is).

I was keeping an eye on this trial too, since my friend is KRAS mutant (no that she's going to be able to go for this at this point).... I don't remember if you're KRAS mutant:
A Study of MEHD7945A and Cobimetinib (GDC-0973) in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS

MEHD7945A is an antibody -anti-HER3/EGFR http://cancerres.aacrjournals.org/cgi/c ... acts/CT-08

Sending good vibes for your kidneys! That was the Avastin : (


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