Anti PD1 trials

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3/31/2012 9:52pm
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Replies: 20

Okay, all these trials are getting so confusing! I am pretty well read on melanoma, but I am a liberal arts kind of person NOT a scientist, so any help would be welcome. My understanding is that BMS has an anti PD1 trial called MDX 1106, which shows on the clinical trial.gov website with one of the sites at Dana Farber in Boston. Yet, when I inquired about this trial at Dana Farber, they told me this trial wasn't open, and the clinical trial website is not up to date, frequently months behind, well that's a problem! Still, I don't understand why this BMS trial is closed. We are meeting with staff at Dana Farber next week as they said there is an opening in their Genentech trial with anti PDL1 drug, but even after reading about this drug not sure I understand the differences between drugs. I know that Cure Tech, Merck, and Glaxo Smith Kline all have anti pd1 trials and we are willing to travel if necessary. We want to make the right decision for Phil's treatment, but I am on a huge learning curve, as now I heard that tumors that express certain proteins respond better to anti Pd1, yet I don't think his tumors have been tested for these proteins. I need a Jimmy B to just tell me what to do, help! Anyway, Phil has completed six rounds of biochemo at MD Anderson, and has cells frozen for adoptive cell transfer, we are just not sure when we will get a slot, and I want plan B ( it's really plan C, D, or E, but who is counting), in place. Thanks for all the support, I love the mpip bulletin, dealing with stage 4 melanoma is hard enough, it's nice to have a place to go to where people truly understand! Valerie (Phil's wife)

melissa ann - (3/31/2012 - 10:31pm)

Valerie, I am right there with you.  I also feel very well educated about melanoma, however, the trial "lingo"  is beyond confusing. My husband is also stage 4 with 3 current lymph nodes affected.   In the last few weeks, we have traveled to NIH for TILS evaluation and then to Moffitt in Tampa for Anti-PD1 evaluation.  NIH rejected him for TILS due to his lymphedema. (too much of a risk of infection)  Moffitt accepted him into a ANti-PD1 trial but I have no idea which one.  I plan on asking when we go for scans on the 20th of April.  I also hope Jimmy B answers you and will help us both understand a little bettter.  I wish you luck in your research and with your husband's treatment.  This really is a wonderful place to meet people who truly understand.  Melissa (Peck's wife)

jim Breitfeller - (4/1/2012 - 9:06am)

Valerie/Melissa,
I am having a tough time getting my reply posted. MRF forum has anti- spam filter and has been not allowing me to cut and paste my reply. So, I may have to reply in a number of posts.

First, here is a paper on PD1 vs PDL-1. It is by Dr Jim AIlison, the researcher that discoveried anti-CTLA-4 (Yervoy).
http://www.box.com/shared/x4Ip733yfz

Best regards,
Jimmy b

jim Breitfeller - (4/1/2012 - 9:08am)

Valerie/Melissa,
I am having a tough time getting my reply posted. MRF forum has anti- spam filter and has been not allowing me to cut and paste my reply. So, I may have to reply in a number of posts.

First, here is a paper on PD1 vs PDL-1. It is by Dr Jim AIlison, the researcher that discoveried anti-CTLA-4 (Yervoy).
http://www.box.com/shared/x4Ip733yfz

Best regards,
Jimmy b

Bubbles - (4/1/2012 - 10:08am)

I happen to be a nurse practitioner and on an anti-PD1 trial in Tampa.  However, all this gets very confusing very quickly.

All the anti-PD1 therapies work like this:  Anti-PD1 is an antibody that blocks a protein that turns off T-cells.  This allows the person's immune system to attack the melanoma cells.  Melanoma cells frequently build their own protective shroud by turning off the immune system. They do this by inducing what should be "attacking" T-cells to produce the protein PD1. The melanoma cells also have receptors that bind the PD1.  Together, these interactions turns off the person's own T-cells.

The research paper (by - Chen, et al) documents this interaction.  There is a possibility that by knowing if your melanoma cells produce the binding protein, you would know that you would then have a greater chance of gaining a positive response to anti-PD1 therapy.  This remains to be proven, however and no trials are (as of now) requiring this info.

The anti-PD1 products are:

Bristol Meyers Squibb = MDX-1106

Merck/Sherring Plough = MK-3475/SCH900475

Amplimmune/Glaxo Smith Kline - AMP-224

CureTech - CT-011

Genentec - no drug name yet....and is technically an anti-PD1 ligand

In Tampa, at Moffitt, they have done many arms of a trial with MDX-1106 combined with vaccines.  For the trials with vaccines HLA typing is required...not for the anti-PD1...but for the vaccines.  I have been told that they are going to do some additional arms WITHOUT the vaccines...but it is best to check with them.  I have also heard that they are starting some additional anti-PD1 trials with other products (not just MDX1106)

Word on the street is that the BMS and Merck products are providing a good number of patients with regression of tumors.  Cure Tech is not doing so well...with NO patients with regression in the US, some with stable disease, but others with progression.  I have heard no results about the Amplimmune or Genentec products.

This was as concise as I could make it!  Hope it helps.  Wishing you all the best.

Celeste

 

 

chaoticallypreciselifeloveandmelanoma.blogspot.com

Phil S - (4/1/2012 - 12:25pm)

Celeste and Jimmy B, Thanks so much for your replies. Jimmy, I can't open your link, says file not available, I would love to email you directly, tried thru this site but I not think you received it. Let me know best way to communicate. Celeste, thanks for information, what exactly is a ligand? Looks like, I need to find Merck and BMS sites, which proves challenging since clinical trials.gov isn't up to date. So, glad for your positive response to MDX1106, keep it up. Take care! Valerie

audgator - (4/1/2012 - 5:54pm)

Bubbles,  (Celeste is a beautiful name, but Bubbles is more fun)

Thank you for a very coherent reply. Also Jimmy, thank you as always.

I am in the non-vaccine arm of the trial at Moffitt, 2 treatments down, 4 (and hopefully 10) to go.

Dan

LynnLuc - (4/2/2012 - 1:39am)

Phase I Pilot Study of Peptide Vaccine Comprising gp100:209-217(210M), MART-1:26-35(27L), gp100:280-288(288V), and NY-ESO-1 Emulsified in Montanide ISA 51 VG and Anti-PD-1 Human Monoclonal Antibody MDX-1106 in Patients With Unresectable Stage III or IV Melanoma

 

The primary objective is

To assess the safety and tolerability of multiple class I peptide vaccine comprising gp100:209-217(210M), MART-1:26-35(27L), gp100:280-288(288V), and NY-ESO-1 emulsified in Montanide ISA 51 VG and anti-PD-1 human monoclonal antibody MDX-1106 (BMS-936558) in HLA-A*0201-positive patients with unresectable stage III or IV malignant melanoma (patients in cohort 6 will not be HLA restricted).

It is the last arm that does not require the HLA typing..this arm does not receive the peptides...just the MDX 1106.

I am in the first trial - Phase I Study of Anti-PD-1 Human Monoclonal Antibody MDX-1106 and Vaccine Therapy Comprising gp100:209-217(210M) Peptide, MART-1:26-35(27L) Peptide, gp100:280-288(288V) Peptide, NY-ESO-1 Peptide, and Montanide ISA 51 VG in Patients With Resected Stage IV Melanoma

in the maintainance phase ...MDX 1106 every 3 months.

 

I go to Moffitt in Tampa and Dr Jeff Weber is my onc.

Advocate for your own treatment.. Stage 4 Melanoma NED Surgery,Radiation, Temodar 300Mg July 2009-March 2010, then Thorocotomy...now "Phase I Study of Anti-PD-1 Human Monoclonal Antibody MDX-1106 and Vaccine Therapy"

LynnLuc - (4/2/2012 - 1:45am)

PS...I have been in the trial for 76 weeks now. Whenever I get my booster of anti pd 1  the peptide injections still swell and react with itching. I continue to get more and more Vitiligo, especially on my shoulders and upper arms. They say this is a good sign....NED 2 years and 5 days!

Advocate for your own treatment.. Stage 4 Melanoma NED Surgery,Radiation, Temodar 300Mg July 2009-March 2010, then Thorocotomy...now "Phase I Study of Anti-PD-1 Human Monoclonal Antibody MDX-1106 and Vaccine Therapy"

TracyR - (4/23/2012 - 10:45pm)

Thanks for your post Celeste. I'm currently on the CT-011 trial in Nashville and after 4 infusions my tumor decreased by 20%. Praying that Gd keeps this stuff working!

Anonymous - (4/1/2012 - 2:11pm)

Jimmy.your link is not working. Please try again. Anon

Anonymous - (4/1/2012 - 2:13pm)

Jimmy..your link is not working. Please try aagain.Thanks

Karin L - (4/1/2012 - 12:18pm)

Thank you for asking this question Valerie and thank you JimmB and Celeste for the replies!  My mind gets so befuddled with this stuff unless it's in abc terms blush.

Karin

melissa ann - (4/1/2012 - 3:11pm)

Hello to all...it is so amazing how much information we can find out from each other on this site.  JImmy, thanks for your reply, I hope to be able to read the links..Your knowledge and info is priceless.  Celeste, thanks so much for your understandable reply.  My husband is a dermatologist with melanoma and he and the doctors often talk the medical language and I leave confused!  After reading your posts I decided that it would probably be a good idea to read the trial consent form they gave us at Moffitt.(DUH!)  I have learned that Peck will be on the BMS trial.  He will be in the arm that does not have the vaccine with it.  He is HLA negative.  This is considered Group 6 and has 20 patients in it.  His first infusion will be April 25th.  Celeste, I have also stumbled across your blog.  I so appreciate your words, humor and information.  We even went to Walt'z while we were in Tampa the first time. 

Valerie, it looks like MOffitt has The BMS trial from what I can decipher from our paperwork.  MY email is magooym@yahoo.com if you ever want to chat.  Many thanks to all!  Melissa (Peck's wife)

jim Breitfeller - (4/1/2012 - 3:56pm)

My email is jimbreitfe@me.com

This is my Ipad address.
The MPIP forum is attached to my home computer address.

I am in NY helping a family member recover from some surgery.

Best regards,
Jimmy b

Bubbles - (4/1/2012 - 8:45pm)

Valerie,

Trials close quickly because folks are desperately working to get in them.  The number of patients/subjects ('n') allowed is preset when the trial protocol is created.  For instance, most of Merck's trials only had 3 patients at the locations that had the trial...including Moffitt.  My trial has 10  NED patients in each of three dosage groups (1, 3, and 10mg/kg) with matching sets for patients with disease for a total of 30 patients in each arm.

Sorry about "ligand".  It is a receptor protein, that once bound, activates the molecule.  Genentech's antibody blocks the PD1 molecule from binding to the tumor cell. Same end result, just a slightly different mechanism.

Hey Dan,

Thanks for the "Bubbles" comment.  My husband gave that name to me years ago...for my effervescent personality!  :>)

So good to hear of someone in the nonvaccine arm!  I am wishing you the best!  You're not missing anything without the vaccines!  Those shots were a challenge!

Melissa Ann,

Sounds like Peck will be in the same group with Dan. That's great!  I wish you both the best.  I'm glad my blog can provide some entertainment and help. I figure somebody needs to be able to see what the lab rat goes through!!!  Hope you liked Waltz!!!  Check out Columbia...downtown....next.  It's great and right between the airport and Moffitt!

Best wishes to each of you.  Let me know if I can ever be of any help.  Celeste/Bubbles

chaoticallypreciselifeloveandmelanoma.blogspot.com

MorningGlory - (4/14/2012 - 10:19pm)

Thank you all for sharing your incredible stories.  I have recently had a recurrence of my anal mucosal melanoma in the general area of my first surgery.  I did the year of interferon and am considering looking into the anti PD1 trial.  Intiially was diagnosed as 3B, now I am likely 3C.  Don't like the watch and wait plan proposed by my onc.  He wants to repeat PET/CTs in 3 mos.  I would rather be proactive in this approach.  Seems that there are many options to consider, and surely I must meet criteria for something.  I am Braf and Ckit negative.  Any input that you have would be greatly appreciated.

Jackie

margaretrogers57 - (5/11/2012 - 12:05pm)

My husband has an ocular primary and mets to liver and vertebrae.  Anyone on list the did pd-1 with ocular?  We see Dr. Weber in Tampa @ end of month.  Thanks, Margaret and Butch

margaretrogers57 - (5/11/2012 - 12:06pm)

My husband has an ocular primary and mets to liver and vertebrae.  Anyone on list the did pd-1 with ocular?  We see Dr. Weber in Tampa @ end of month.  Thanks, Margaret and Butch

shari - (8/17/2012 - 9:10am)

Hello Everyone!

My name is Shari Alcorn and my husband Ted was diagnosed with Stage IV Melanoma in Oct 2009.  Had a brain tumor resected and then found lung mets.  He went on Temador which worked for about six months and then went into the Compassionate use trial of Yervoy/Ipi.  He was stable for a year and then went on it again, thanks to the pharmaceutical company paying for the drug.  he again was mostly stable but now has mets on an adrenal gland and in some lymph nodes.  The adrenal gland is the one that is growing so we were referred to Lee Moffitt for the anti pd1 trial.  He starts on Sept 20.  We're nervous but we always are.  I've read all there is and this sounds like the ssecond best option for treatment after adoptive cell therapy.  We're waiting to try that as we are both still working and don't wnat to take that much time off yet.  It was good to read the posts about the anti pd1 and we're really optimistic about Ted's outcome.

Thanks for being there and if any of you are going to be in Tampa let us know.  We will be staying with friends but would love to talk to other survivors!

Shari and Ted

The farewell tour has not begun!