ipi and nivo EAP

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7/10/2014 11:47am
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Replies: 10

BMS has launched an Expanded Access Protocol for the combination of ipi and nivo, their anti-CTLA4 and anti-PD1 drugs. Earlier this year both Merck and BMS opened EAP programs for the PD1 drugs alone.

The combination of ipi and nivo has some very strong results. In one study, 88% of patients with metastatic melanoma were alive after two years. Side effects are a concern, with about 2/3 of paitents having Grade 3 or Grade 4 toxicities. The doctors involved with the study felt that these issues were rather easily managed.

This was just announced this morning, so no sites are open yet. As we have seen, sometimes these sites do take a while to open.  For more information you can go to the EAP posting on clinicaltrials.gov.  

Some details:

--mucosal melanoma is included

--must not have had prior treatment with ipi

--brain mets are allowed, if MRI confirms no progression in 2 weeks

I hope to have more information soon, but in the interim here is the link to the posting:

http://clinicaltrials.gov/ct2/show/NCT02186249?term=nivolumab+melanoma&t...

 

Tim--MRF

Bubbles - (7/10/2014 - 12:48pm)

That's GREAT, Tim!  Thanks for getting the word out!  Celeste

chaoticallypreciselifeloveandmelanoma.blogspot.com

Anonymous - (7/10/2014 - 4:14pm)

Couple of problems, no previous treatments allowed and there are no locations yet.  The study was in a small group so I am not sure I would count on it yet with the side effects being really harsh.

Anonymous - (7/10/2014 - 6:58pm)

Wrong.  It certainly does not say NO TREATMENTS ALLOWED.  And any EAP is not available at sites THE DAY they announce it will be made available. 

BrianP - (7/10/2014 - 11:31pm)

Cooper,

Why do you have to be so harsh with your responses?

It looks like the only disqualifier from prior treatments is Ipi.  That is good news.  Also good news if you are Braf Positive you don't have to have failed Braf treatment.

I hope the timeline is quick.  Tim mentioned 6 - 8 weeks on BMS's part in another post.  At my facility they have a board which also has to approve the treatment being administered at their facility.  Not sure if other facilities have the same requirement but I imagine they do.  This process can take weeks also.  Hopefully it can be done concurrent with the 6 to 8 weeks and not in addition to it. 

My WAG (Wild A*& Guess) is 2 months before first patient is treated but could be upwards of 4 months. 

I think this is absolutely fantastic news for the melanoma community.

Brian

Bubbles - (7/10/2014 - 11:33pm)

Brian,

I just love you!  C

chaoticallypreciselifeloveandmelanoma.blogspot.com

RJoeyB - (7/11/2014 - 6:40am)

[I also posted this in Tim's other update thread about this EAP, apologies for the double-post, just trying to be thorough...]

Also remember that BMS has announced a separate EAP for nivolumab alone for patients who have already tried and failed ipilimumab.  I think it was announced in May and while details on locations have thus far been scarce, we're still in that 6-8 week period where they're still ramping things up, I assume.  Hopefully there will be more details about enrollment opportunities forthcoming very soon.
 
Joe
 

arthurjedi007 - (7/11/2014 - 10:50am)

"Prior treatment in any Nivolumab or Ipilimumab clinical study (including those who have been randomized to control)"

So if you had ipi the FDA approved way (ie: not clinical study) you are not excluded then?

Bubbles - (7/11/2014 - 3:20pm)

Artie,

I fear no prior ipi at all will be allowed. Since in the "inclusion criteria" it states that patients must be ipi naive.  While the exclusions are difficult for many, I think I am most upset by the statement that, apparently, folks who never really got ipi or nivo because they were in the control arm of a study, can be excluded as well.  I'm hoping I'm wrong about that, but that is what it seems to say.

Best, celeste

chaoticallypreciselifeloveandmelanoma.blogspot.com

RJoeyB - (7/11/2014 - 4:21pm)

This isn't intended as a justification for BMS, only an observation.  Merck's MK-3475 pembrolizumab EAP has this in it's own exclusion criteria.  From:

Frequently Asked Questions about pembrolizumab U.S. Expanded Access Program
 
Are patients from the control arms of any pembrolizumab studies eligible?
No, patients who were on the control arm of any pembrolizumab studies are not eligible to participate in the expanded access program.
 
I can't say for certain the reasoning or if there is specific FDA regulation involved in making this decision, but I'm guessing that that thinking goes as follows...  these EAPs are being established because of the incredible results that are being observed in Phase II trials as well as yet-to-be-completed Phase III trials.  Final FDA approval won't be granted to any of these therapies until the Phase III trials are complete.  Even Merck's expected October approval won't be for pembro as a first-line therapy (at least prior ipi will be a condition).  Once that Phase III trial is done and submitted, the approval will then be revised and pembro can be a first-line therapy.  In the meantime, if patients in the control arms of existing therapies were all allowed to effectively cross over to the EAP, this would effectively end all of the Phase III testing.  And for patients who have had disease progression, they would need to "unblind" all the arms to determine who received what, also effectively ruining the study results.  There are some well-constructed studies that have crossovers built into them, but plenty that aren't.
 
Again, not defending it in any way, I'm a four-year Stage IV fighter like many of you just trying to understand how these things work so I'm prepared to make the right decisions if/when the need arises.  Issues like this are ugly, even more so being so close to it, and I wish there were better answers.  
 
Joe
 
 

arthurjedi007 - (7/11/2014 - 6:59pm)

Ok. Thanks Celeste and Joe. It doesn't chemically make sense to me. I would think if ctla-4 doesn't work because the mel cell has pd-1 blocking it. Then pd-1 doesn't work because the mel cell has recreated ctla-4 blocking it. Then doing both at once might work. I remember having that type of conversation with my local doctor when I was doing ipi. He seemed to agree with the logic. But who knows. I guess it all comes down to rules, regulations, side affects, money, etc. I'm counting on merck's eap pd1. I've had 3 doses so far but I don't want to get my hopes up too much yet because so many meds have failed me but the past 2 days the tumor on my skull is significantly smaller so I'm really encouraged by that. The big one on my shoulder and lymph node haven't shrank yet but are same visible size so I take that as good too.