merck MK-3475 - Part C criteria??? or now what? - 1258640

gaw1
Posts:18

Hi All,

My brother was trying to get into the Merck MK-3475 trial out of UCSF as first line for recurrent Adenocarcinoma NSCLC. He was slotted for Part F: which was for NSCLC with PD-L1 gene expression. Unfortunately his tumor did not test positive for the PD-L1 expression. He is being advised to go back to original plan of chemo (Carboplatin/Taxol/Avastin). He is also being told that his recurrent is pleural based and he the tumor(s) are scant. He did have quart of fluid buildup that had to be drained early in July.

I thought I read that Part C was for NSCLC patients that did not have the PD-L1 expression. Does anyone know? He is going to call the doctor in the morning to ask, but they didn't mention Part C as an option and I'm hoping to give him some information he can use in his conversation with the doctors.

I thought I read that 13% of patients without PD-L1 expression respond, but I don't know if that was lung patients or melanoma patients or one drug company and not another. Is there a big risk passing up standard chemo for a PD1/L1 type trial when no PD-L1 expression is found on the tumor?

Any other thoughts on trials to pursue / research? Trying to do some research this weekend. It has been 6 weeks since the recurrent diagnosis and with failing to get into the trial, he is anxious to get started with a treatment plan. Any thoughts appreciated.

GAW

NSCLC, Adenocarcinoma 2A Feb 2012, Male Non Smoker 47, surgery and chemo. Reoccurrence in lung July 2013. Brain and bone scan clean.

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Reply # - August 15, 2013, 08:51 PM

Dr West
Posts: 4735

GAW,

You're correct that responses have been seen in patients who don't have PD-L1 expression, and they aren't rare, which leaves me and many other lung cancer specialists feeling that the trials that exclude such patients are really limiting their potential population of beneficiaries needlessly. I presume that they want to use the "crizotinib-like" approach of focusing on a narrow population and showing a huge response rate that will lead to quick approval of the drug after a small trial -- and then they can work on its approval in a broader population after doing a much larger trial that will hopefully show a significant but presumably less dramatic benefit in those without PD-L1 expression.

I can't speak to the specifics of a trial I'm not participating in. Good luck in learning more.

-Dr. West

Reply # - August 18, 2013, 06:35 PM

carrigallen
Posts: 194

I cannot speak to any specifics, but I would generally guess the reason a patient is not offered to enroll on a part of a trial is because there may be no slots, or that part of the trial may be closed. It seems that slots for these non-randomized trials have been in short supply at many centers.
It seems like it would be reasonable to ask about any other clinical trials of other new drugs in your area. In general, it is helpful to choose both a treatment plan and physician who you feel comfortable with, and don't rush in to a treatment plan just because of anxiety. Good luck!

Reply # - August 19, 2013, 04:12 AM

luke
Posts: 101

Quick question for the Doctors - in your experience, what are the opportunities for a non-US citizen/resident to participate in trials such as the MK-3475 if we are willing and prepared to commute to the US as regularly as required? Is this an impossibility (or a near impossibility) due to the red tape or legislation or criteria involved, or is this just something which will likely be cost prohibitive?

Sorry to hijack the thread GAW.....

Reply # - August 19, 2013, 05:51 AM

carrigallen
Posts: 194

Re: Luke. I think cost may be biggest consideration. We have certainly treated patients on clinical trials who come from other countries. Most of these antibodies are administered every 2 weeks, so at the minimium you are talking about commuting every 2 weeks until cancer progression or toxicity. You also need someone to potentially serve as a caregiver and, in the case of a contingency, being prepared to stay nearby for a week or more.You can also read about the experience of other patients on this forum that have flown back & forth. from Midwest to West coast or East Coast.

Reply # - August 20, 2013, 08:50 PM

gaw1
Posts: 18

Thank you Dr. West and Dr. Creelan. You all provide a wonderful service.

Turns out Part C of the Merck trial is closed/finished so there are no spots regardless of pd-l1 status.

So my brother will be starting chemo in the next two weeks. Likely Carbo/Taxoll/Avastin.

Luke, if you read FeistyD's story she has been on the Merck drug since May 2012 and her July 2013 update said she was still getting every three (? maybe two) week infusions. Success would have you visiting the states a great deal.

I looked at the Merck trial and it appears they are taking patients in Australia, Canada and France. http://www.clinicaltrials.gov/ct2/show/NCT01295827

The Genentech trial lists a number of European sites but they have yet to start recruiting. You might try calling the Genentech number listed in the trial link below and ask for the trials coordinator's contact info at the site in the closest city/country. Then call the coordinator. They may be able to tell you when they will start. My calls into Stanford and a place in LA were returned within 30 minutes by the most helpful people, like angels. http://www.clinicaltrials.gov/ct2/show/NCT01846416

I did some research over the weekend using the advanced search feature of clinicaltrials.gov site on all the pd-1/pd-l1 trials for the BMS, Merck, Genentech drug for lung cancer patients. These are the ones I found. (I'm not a doctor, so this may not be an exclusive list but perhaps a place to start.) My brother didn't qualify for these but your father might.

NCT01295827 http://www.clinicaltrials.gov/ct2/show/NCT01295827
NCT01846416 http://www.clinicaltrials.gov/ct2/show/NCT01846416
NCT01454102
NCT01840579 (Japan only)
NCT01629758
NCT01714739
NCT01903993
NCT01673867
NCT01905657
NCT01693562
NCT01750580
NCT01633970 (may not be for lung cancer)
NCT01375842 (closed to lung cancer patients)

Reply # - August 21, 2013, 01:54 PM

ssflxl
Posts: 204

Dear Drs.

As I read more about anti-PD 1 studies, I wonder if it's not better to have immune therapy before one ever gets chemo. In a lot of these studies where anti-PD 1 is used, the patients have all been heavily treated before - with 2-3 lines of chemo. After that kind of assault to your immune system, it is a surprise to even have some kind of immune response left. That's why I would like to get on the anti-PD 1 clinical trial before chemo. I feel that it is better to have this treatment with an intact immune system, or maybe have it be given with chemo at the same time so you can get the tumor in 2 different ways.

what are your thoughts?

thanks

ssflxl

Reply # - August 21, 2013, 03:44 PM

carrigallen
Posts: 194

RE: ssflxl. I think it is too soon to make any conclusions about the activity of anti-PD-1 or anti-PD-L1 before vs. after chemotherapy. In principle, the drugs should work in both settings.

While the body's immune system may be less robust after chemotherapy, many studies also suggest that is easier for our bodies' T-cells to recognize tumor cells after chemotherapy or radiation is given. This may be in part because the tumor releases more proteins when its growth is stopped.
For example, in a preliminary study of Yervoy (ipilimumab) for lung cancer, it appeared to be more active when two cycles of chemotherapy were given first. Ipilimumab and nivolumab (anti-PD-1) have some similiarities in how they activate T-cells.

Despite the promise of anti-PD-1/PD-L1 as a single drug, only a small proportion of lung cancer patients respond to these drugs. So new immunotherapy approaches or combinations still need to be developed.

Reply # - August 21, 2013, 10:09 PM

Dr West
Posts: 4735

I'd also just point out that many of the people who have done very well on nivolumab, which started the wild frenzy of interest in immune checkpoint inhibitors for lung cancer, had been heavily treated with prior chemotherapy before doing very well on the investigational immunotherapy. Would patients do even better if the immunotherapy were given prior to chemo? Perhaps, but not necessarily. I wouldn't make any such presumptions in the absence of data on the subject.

-Dr. West

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