How much MK-3475 is too much?

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5/1/2014 4:44pm
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Replies: 17

Hi there!

After reading several of your stories and looking at all the information out there, I realize I am one of the lucky ones to have qualified for the pd1 MK-3475 trial.  It appears too, from what I am reading, that even the dosage I am getting (the highest dosage) seems to be the dosage with the better results.

But part of the trial I am in, is that they are trying to figure out how much of the drug is needed for the best results.  Which brings me to my biggest question:  How much is too much? 

I originally was signed up for two years.  Then a year into treatment, they changed it and had me sign new forms saying "no end date."  Saying that I could be on it for the rest of my life. 

I am having a great response so far and am so thankful for that.  But I am struggling with how long I should actually stay on the drug.  And I am struggling with the fact that if I bow-out and come off of it, they will not offer it to me again.

Ideally, I'd like to do my original two-years and then come off of it and see how things go.

Has anyone out there been on it for a long time, come off it, and is still doing great?



Hi Laurie,

I took Nivolumab (the BMS anti-PD1 product) for 2 1/2 years at only 1mg/kg dosage.  I remain NED having had my last infusion in June 2013 (almost a year ago).  It was a Phase 1 trial (as I assume yours is as well) and yes, with those, the only real question is a dosing determination....both in mg/kg dose as well as duration of administration.  Dr. Weber  has said that 3mg/kg will probably be the best dose (most effective with least side effects) and has also mentioned that he feels that the 2 1/2 years the folks in my trial took the medication was probably longer than necessary.  However, all of that remains to be seen.  Wishing you my best.  Celeste

Anonymous - (5/1/2014 - 5:42pm)

I am on MK3475 for  2 + yrs on the 10 mg. As much as I want to get off the drug, I was told that Merck will give  NO guarantees to give patients the drug again if they recurred and/or let them back on the trial. Therefore I will NOT take the chance to come off the drug unless I had it in writing from Merck to let me back on the trial if I recurred.

My doctor and others specuate at my clinical trial site  that when the drug is approved by the FDA, the chances are zero that Merck will let me get the drug free and/or resume the trial. Such is life so I deal with side effects and happy to be NED! Plus I cannot afford to pay for the drug under Medicare.



Anonymous - (5/1/2014 - 6:40pm)


Has Dr.Weber mentioned if patients on your trial have a recurrence that BMS will give them the drug again and/or letthem in the trial again? Has anyone in your trial in fact had a recurrence?

Thanks for your input. You add such valuable info to this forum!

Celeste, if you don't mind me asking, what side effects did you have during treatment?  And did they all go away after coming off of treatment?

I have been pretty lucky and my side effects are not bad, but it can be scary from time to time and I worry that some of the effects will be irreversible.  For instance, if I take the drug too long, and more severe side effects pop up, that those will be a never ending problem.


That's a very interesting question and I'm interested to see what Celeste says about that as well.  She talks a lot about her side effects in her blog and I remember her talking about the cumulative effects of the drug over time.  I did hear something recently about the effects of Nivo getting less over time rather than worse, i.e. your body learns to live with nivo.  I never tried to track down that study though so I can't vouch for that info.


Ok, guys!  Let me see if I can give this a go!!

As for as BMS continuing our meds....  About 6 months before my last dose, Dr. Weber asked me whether I wanted to continue to take Nivo, longer than the original trial plan of 2 1/2 years.  When I asked what the options were...he said he wasn't sure, but that there were some patients who wanted to continue and he was willing to go to bat for them with BMS and try to make the continuation happen.  I said that I doubted that I would want to continue...but would be interested in the BMS response.  They said, "NO!"  I think Dr. Weber was a little surprised...but, I was not.  I've just been in this game too long I guess!  Addtionally, I was not dissapointed.  I am convinced that the amount of drug I was given was going to give me a response if I was going to get one at all.  From what he has said, that is what Dr. Weber thinks as well.....but as I said before....the truth will out....and we are getting ever closer to that answer as more of us finish these sorts of trials.

As far as BMS "letting" me take Nivo a reinduction should I need it....  To back up a step, I have talked with Weber about what he would recommend I do, should I have a recurrence.  He very quickly replied that he would suggest I try a Nivo reinduction (much like folks do with ipi these days) or take ipi.  Would BMS allow me back on a trial????  I haven't specifically sought to answer to that question, but it is doubtful. No person (that I know of) has been allowed to gain access to an anti-PD1 trial if they have already been given anti-PD1 of any sort.....even if it was the crapy Cure Tech version that apparently worked for no one!!!  However, once any of the anti-PD1 products are approved, of course I could take it if an oncologist prescribed it for me.  It would be handled the way ipi is handled now.  And I do think either the BMS or Merck product will be FDA approved relatively soon.  How insurance companies will cover the drug at that point remains of course that will be a big issue for many.

As far as recurrence after anti-PD1....sadly, yes.  Many folks have experienced recurrence as anti-PD1 products are effective in only roughly 30-40% of cases. Only in melanoma world is this a wonderful number!!!  My study started  as 2 cohorts, with three arms each.  The NED cohort and the NON-resected cohort...both Stage IV.  I was in the NED group.  Both of those groups were further divided into dosage groups....getting either 1, 3, or 10mg/kg.  I was given 1mg/kg. We were all given Nivo every 2 weeks for 6 months, then every 3 months for an additional 2 years.   In my NED best as I can ascertain:  33 patients were treated.  9 relapsed.  4 are deceased.  3 are subsequently in remision.  2 are in treatment currently.  I cannot tell you for certain what treatment those who are currently being treated or regained remission were given...only that Dr. Weber has told me and stated in various articles that folks who had already been given anti-PD1 have responded well to ipi and vice versa.  (By the way, when my trial first started, prior treatment with ipi was not allowed, but subsequently arms were added allowing those patients and some of those have done very well.)  But, back to my "results"...without treatment, Dr. Weber has said that the folks in my group, given our disease trajectory, would have caused him to expect that at this point, there would have been 16 deaths, rather than the 4 we have lost.  Overall, those of us remaining have an 87% survival rate at 2 years.  In the NON-resected group...105 patients.  Median survival has been 16.7 months.  This is equivalent to a prior Nivo study in which 107 were treated, but were given the med every 2 weeks for 2 years.  Their median survival was 16.8 months.  Dr. Weber feels this is very significant data as his patients did just as well (if not better, as he allowed sicker patients in his trial) and were given less med, and had to spend less in time and treasure in treatment.  He will be publishing data regarding both of our groups...and probably some preliminary data on additional arms that were added....including one that allowed untreated brain mets!!! ASCO in June.  Here is a link addressing the results and my last f/u visit in March that might give you some more info:

As far as side effects....Some problems caused by anti-PD1 can be hypothyroid function....which at least one lady in my trial experienced (she was in my group...same dose).  On the good side, it can be treated with daily synthroid (thryroid replacement).  Folks can get some of the same side effects as when on ipi....rashes, fatigue, and arthralgias are very common.  Bad stuff like colitis and pneumonitis can happen too....but if caught early, are reversed fairly easily with a discontinuation of the med and steroids.  Here is an overview of anti-PD1 in general from my blog:

This is a post in which I tried to explain the side effects of anti-PD1 and why you get them:

There is another rather long post right after the one noted above, where I went back and really looked at the side effects I had and when, if you are interested.  But this it sort of my "sum up":

And this is a post after my last Nivo infusion in June, 2013:

So, my final comment on side effects:  Dr. Weber and I have a running disagreement in that he has said....though I think he is coming over to my side as time pases....that side effects with Nivo are NOT cummulative.  I disagree....and I've lived it...he has not!!!  I don't mean that they become unbearable over time....but I've studied my own time line of side effects at this point....and yes....the rash, though it was rather intermittent....was worse when it did come...later.  The side effects of joint aches, rash and fatigue....came sooner after infusions once I had had dose 4...probably when the 1/2 life of the drug converged so that it was staying at a pretty much stable level all the time.  On the bad side....I had pretty horrific mouth ulcers by the end of my treatment.  On the good side....while some other patients developed mucositis....tender lips, tongue and gums....nobody else developed actual ulcers.  Also on the good side....though I pretty consistently developed some resp symptoms after infusions....I never had pneumontitis, colitis, or problems with my thyroid.  I did have fatigue...but worked full time throughout and continued to run and do work outs as well.  I'm not sure that was always the smartest approach...but I'm just that stubborn...and for was a good thing.  Since being off the drug....I still have occasional rashes and arthralgias.  As my daughter used to say...."Random!!!!"....and they are.  The tiredness and respiratory symptoms are gone.  And though I have had two flares of mouth ulcers since stopping....they have not been nearly so bad as they had become when I was finishing.

Hope that helps.  We are all different, so I don't expect that anyone's path will be identical to mine....but I would have liked to have known some of this when I was the 9th patient signed on!!!  Hang in there.  I wish you all my best.  Celeste


Thanks Celeste.  Great info.  I'm really looking forward to Dr. Weber's presentation at ASCO.

Celeste, you are fantastic!  For all you share to try and help others.

Thank you so much for taking all that time to write that information. 

I saw my dermatologist on Friday.  I asked him about 5 white perfectly round spots on my forehead and shoulder.  He mentioned what you mentioned on your blog...that it is considered a good sign that the treatment is working.  I guess you would call those white patches Vitiligo. 


I went through the exact thought process you did in March.

I've been in the MK-3475 trial for a bit over 2 years now.  I thought it was a 2 year trial and did not realize that it had been increased in duration as the various arms were added as I signed revised clinical trial agreements since the agreements don't speak to the trial's duration.

I'm NED now with minimal side effects and so very thankful for the treatment.  I'm also on the 10 dosage group.  My biggest problem is a variable amout of fatigue which sometimes gets in the way of "moving forward".  I also have a trip to make every 2 weeks to The Angeles Clinic for the infusion.  I'm also concerned about the radiatioin I get from a CT scan (I have a pacemaker) every 12 weeks.  At this point it seems perhaps overkill but it required to remain in the trial.

I've decided to stay in the trial for at least another year and review my decision in a year.

I know that Merck is trying to rapidly commercialize MK-3475 so it appears to me that their intent is that you continue to take it "forever" since there is very limited experience with patients who have stopped the treatment.  I know there is excitement that the treatment is durable even if stopped but that is based on a very limited group of patients.



Anonymous - (5/2/2014 - 10:27am)

Hi everyone.


I have read post from a patient  whose name is Rober Bruce. He is with UCSF,Dr.Daud on the Merck 3475. He is NED & DR. Daud told him that he could stop taking the drug and Merck would let him back on the trial.

I am confused. Why does he get to stop and other  people like Laurie & Walt need to keep taking the drug because Merck will not let them get back on the trial if they recur?

I did not state that Merck would not leave me back it.  It appears if I stop that they will leave me back in.

A section was added to the last Cliniical Trial Agreement revision I signed in part stating "you may be eligible to receive additional doses of the drug.  Your study doctor will determine if you meet the requirement for the Second Course Dosing."................

This applies if your disease starts progressing again after leaving the trial (assuming the drug worked in the first place).

I was aware of this when I decided to continue in the study.

Ohhh Walt, you just made my day.  I am going to go back and read my contract over again. 

Thank you all for your help.  :)


Just read everything again and no, I do not have that section in my contract.  :(

I will bring it up at my next appointment with my doctor.

Thank you everyone for your help.


Anonymous - (5/4/2014 - 12:46pm)

Laurie, that would be great if your doctor to clarify for us the requirement s to get back in the trial if we stop. May I suggest you start a new Topic so other will see your comments in case they did not read this thread.


Anonymous - (5/2/2014 - 5:29pm)

Walt, you stated "you may be eligible to receive additional doses of the drug" that is NO gurantee from MERCK. Even you Doctor cannot gurantee you will be eligible:  "Your study doctor will determine if you meet the requirement for the Second Course Dosing."

Without a guarantee to get the Second Course Dosing, I would not take the chance to stop taking the drug & stop the trial unless you can afford to pay for the drug via insurance.

Just my 2 cents

That is exactly my husbands thinking only he was on Yervoy (Ipi) at the 10 mg/kg.  So when he was NED for 1 year he went off of the trial but until that time he had the initial 4 infusions in 12 weeks and then every 12 weeks after he was given an infusion.

He also worries about all the radiation from all the scans so he now gets those every 6 months.

If you want to read more check out his profile.

Judy (loving wife of Gene Stage IV and now NED)

Live 4 today. Thank God for all he has done for us. Looking forward to enjoying tomorrow.

Update on my MK-3475 PD1 drug trial:

I just saw my doctor yesterday and I signed a new contract for that trial.

They finally added the paragraph that I have been waiting for......

"Second Course Phase:  If you have a good response to the study drugs and stop receiving MK-3475, but then your disease begins to progress again you may be eligible to receive MK-3475 study drug. Your  doctor will determine if you meet the study requirements for the Second Course treatment.  If you are eligible, you will restart treatment and will be retreated at the dose and dose frequency you received upon initial treatmnet with MK-3475". 

I am not going to make any decisions about coming off the drug trial just yet.  I am just glad to see I am not trapped with the "no end date" for treatment anymore.  Makes me feel more like a human that is allowed to make her own decisions for her body rather than a lab rat that is being studied and told what to do.

Have a great day,