MEDI4736 - 1260483

Hi Mike!

Thanks so much for introducing us/me to the new drug in the anti pd-l1 race. I hope you don't mind but I pasted a link to the search results from clinicaltrials.org to MEDI4736 not knowing if any of the 3 is the one your on. I'll plan on hearing good news from you for Thanksgiving.

http://clinicaltrials.gov/ct2/results?term=MEDI4736+&Search=Search

Welcome to Grace and please keep us posted.
Janine

That's great to hear. We would LOVE to learn of another potentially very effective, well tolerated anti-cancer therapy that has the promise of working well in many different cancer types. Please share your experiences, hopefully a great success, but we'll be very interested no matter what.

Good luck.

-Dr. West

Thank you so much for letting us know. . .and best of luck to you on your upcoming scan!

Laya

Hi Mike,

I'm on your blog now....and as you know, I'm now in the process of being screened for the MEDI-4736 trial at Memorial Sloan Kittering in NYC.

Here is the trail description:

http://clinicaltrials.gov/ct2/show/NCT01693562

Bill Drake

Stable is great...no wonder he was smiling! And so are we! Thanks for sharing your good news.

JimC
Forum moderator

Great Mike!

Good to talk to you yesterday....I will keep you posted on my progress at Sloan.

Sounds exciting, let's hope for the best. We would know very little about cancer if not for courageous and hopeful participants on clinical trials, like you.

mrkenney, Stable makes me cautiously smiley. I've heard of some people having progression then shrinkage on some of the immuno drugs.
Congrats for stable and the lack of side effects.
Best,
Janine

Mike,

How's it going?

Bill

Wow, great news mrkenney, Congratulations! I hope to hear NED or whatever it's called continues on well past Oct.

Bill, did you ever get into the trial?

Janine

Great to hear! Thanks for the update.

-Dr. West

mrkenney,

Were you tested for PDL 1 prior to entering this trial? if so, are you positive for PDL 1?
congratulations for the great response.

ssflxl

Hi Mike,

I'm trying to get in a trail, #NCT01975831 study in Boston at Dana Farber with MEDI4736 in combination with Tremelimumab. It's being run by Dr. Patrick Ott. The trail is also being done at MSKCC in NY with Dr. Maggie Callahan.

I have have been receiving Docetaxel - 6 infusions so far. Not any real side effects except loss of hair. My last scan showed that the lymph nodes have not been growing, and no mets.

I would love to connect with you again by phone. here is my email:

bdrake103@gmail.com

- Bill

Dr. West,
Question: I had some of my cancer tissue (extracted on Sept 11, 2013) tested for PDL1 at Medimmune as part of my screening for a MEDI4736 trail at MSKCC. I have requested their report on the test, but have been told that because it was testing for a trial, and was done blind, and I can't get a report. The trial Doc at MSKCC, Dr. Segal was called with the result — negative. I have learned that the test is not 100% conclusive, and that the tissue needs to be fresh. I just want to ask what you think of this situation.
Thanks, Bill

Mike - thanks for the info! So after all, you did test positive for the PD-L1? Did Medimmue do the testing? Bill

Mike - can I ask who your oncologist is? Thanks, Bill

Janine - I have not getten into a trail yet....still working on it! I'm was close with the IPI/NIVO trail at MSKCC, but I had an infusion of Docetaxel, and the scan showed that the nodes shrunk, so that put me out of contention. You ned to be "unresponsive" to any chemo to qualify. I missed out on the MEDI4736 at Sloan because I was tested negative by Medimmune for PD-L1, but I question that result. Bill

I'm sure you have this info but just in case, For more information about this study and to inquire about eligibility, please contact the office of Dr. Neil H. Segal at 646-888-4187.

I'm sorry you're having difficulty with testing. I've heard chatter about fresh biopsies but nothing specific or conclusive. I'd think if there isn't a standard of testing then each trial selects the test to be used for continuity. Too I noted in the trial inclusion criteria listed on http://clinicaltrials.gov/ct2/show/NCT01693562 , "Available archived tumor tissue sample" and "Willingness to provide consent for biopsy samples (dose-expansion only)" was needed. curious.

I'll ask Dr. Pennell to respond also. He has been active in molecular testing and may have input here.

All best,
Janine

Hi Bill, I know that the issue of PD-L1 testing and what the results mean can be confusing. PD-L1 is a protein on tumor cells and tumor stroma (the normal non-cancerous tissue in a tumor) that binds to PD-1 on immune cells and causes the immune system to turn off, allowing the tumor to escape destruction by the immune system. The drugs targeting PD-1 and PD-L1 interfere with this process. The idea behind looking for the presence of PD-L1 in the tumor is that blocking this system seems to be more effective when the PD-L1 is there. Perhaps if it isn't there then the PD-1/PD-L1 system is not preventing immune attack and giving the drugs won't do anything.

There are several issues with this assumption. First of all, every company uses a different method to define "PD-L1 positive", using different antibodies and different cutoffs of what is positive or negative. So theoretically a biopsy could be called "PD-L1 negative" by one test and be called "positive" by another. Second, PD-L1 expression can vary from area to area within a tumor or even in different sites of spread within the body, so any one biopsy may not reflect the whole cancer; i.e. they just may have missed the part that was positive and biopsied a negative area. Finally, PD-L1 expression may change over time and with treatment. If the tissue being tested is from the time of diagnosis and is negative, it is possible that later on after radiation or chemo that a new biopsy could be positive. All of these are hypothetical but this illustrates how little we really know about this biomarker.

We do know that some patients labelled "PD-L1 negative" still do respond to immune checkpoint inhibitors, and my guess when that happens it is for one of the above reasons. Since most trials require PD-L1 to be positive, then the options would be to be tested again using another test (or with another biopsy), or to enter a trial that does not require a positive test.

Dear Dr. Pennell,

Thank you so much for so perfectly articulating the issues with the PD-L1 testing as we know them at this point in time.

Should I have requested to Dr. Neil Segal at MSKCC to do more testing on new tissue before I let them toss me from the trial? After reading your assessment, I wish I had.
Bill

Well, it depends. If the test was on an old biopsy then a new one is reasonable to consider but certainly not trivial and depends on how safe it is and whether the cost would be covered by the study. If the test was on a recent biopsy then I am not sure how likely a running of the same test would be to show something different.

Mike - the study is at Georgetown U Hospital?

Hi Mike,

I found info on Dr. Michael J. Pishvaian @ Georgetown University Hospital...thanks.

But I can't find any info on your trial and/or Dr. Ion Cotarla on the GUH web site? Thoughts?

Bill

This is the only clinical trial I could find with a location in Washington, DC. This might be the one he's on.
Take care, Judy
http://clinicaltrials.gov/ct2/show/NCT01693562?term=MEDI4736+and+NSCLC&…

I'm sorry. We've generally found that the extreme interest in immunotherapy trials leads to it being a race to get patients on trial before the trials close, often very rapidly.

-Dr. West

Hi, I'm new here! Been following Mike's progress -- was so excited to see his post re latest scans. I do have a personal interest in MEDI4736, too...

I have Stage 4 lung cancer and am in a clinical trial of MEDI4736 and tremelimumab at Moffitt Cancer Center in Tampa. Not where Mike is reponse-wise (yet!) but all my mets that they're tracking -- brain, adrenal gland, 3 smaller lesions/lymph nodes -- have shrunk dramatically. My primary tumor is not precisely measurable, I'm told, b/c I had radiation on it earlier this year and edges are fuzzy/blurry on CT; it's also not a study "target lesion" b/c of recent radiation anyway. But radiologist reports in April and June (started treatment in Feb.) called it "grossly stable." Next scans Aug. 7!

[Sorry, don't have time to learn the cancer shorthand right now.)

Why I really got on here is to tell Bill about another clinical trial which he hasn't mentioned and perhaps hasn't investigated: http://clinicaltrials.gov/ct2/show/NCT01975831?intr=MEDI4736+tremelimum…

It's with the same 2 drugs I'm getting and for people with "solid tumors." It's based at Ludwig Cancer Research Institute in NYC. And listing says they're recruiting.

No PD-L1 testing, but I don't know if your current treatment would make you ineligible. Listing says this:

"Failed to respond to or relapsed following standard treatment, or declined or was not eligible for standard treatment."

Maybe you already know about it, but thought I'd post it just in case you don't!

Best wishes, all--

Beth

Hi Beth,

Congratulations on your great results so far, and thanks for the helpful information.

Positive thoughts your way for excellent scan results on the 7th!

JimC
Forum moderator

Hi Beth!
Thanks so much for reaching out with your experience and info on MEDI7436.
I've been trying to enter a MEDI7436 trail — no luck yet. I'm working with Dr. Christopher Azzoli at MGH.
I have a scan scheduled for early September, so we will see if the Docetozel is still working.
- Bill

Hi, Bill--

Oh, I thought you were in NYC! Presuming that MGH is Mass General, please note that the MEDI4736 + tremelimumab trial I sent the link for also has a site in Boston. There's a third site in Buffalo.

The trial I'm in is still recruiting but is strictly for lung cancer patients, which is why I didn't provide details. Sites are Los Angeles, New Haven, NYC, and Tampa. Here's a link to info about that study for anyone else who may be interested:

http://clinicaltrials.gov/ct2/show/NCT02000947?term=medi4736+tremelimum…

-- Beth

Exciting to hear your good results from the trials. Congratulations!
i am off treatment and waiting patiently for PDL1, 3rd phase trial in CA. This is different from the one discussed here. Truthfully, i am very confused with all these trial, i will keep my hope up in the positive way, ***** the one i get must be good!*****

I don't want to muck up the conversation frivolously but I just have to...say congrats Beth even brain lesion shrinking! The post rad fuzzies do last a while.

gigy, I think you're right the one you get's going to be a good one!

Mike, I hope docetaxel is working well without too many side effects. As I'm sure you know if the side effects are deemed too difficult it's thought of as no longer effective.

mrkenney, YaY!

Hi Catdander (Janine?):

Thank you.
It is worrisome to wait for their selection process without any kind of treatment.
i applied for phs 3 trial, which is a comparison trial with Docetaxol. Phs 2 is strictly PDL1 drug only. i am thinking about changing the program if i can.
Do you know what is the "reasonable time" to be off any kind of treatment?
Thank you for any advise and sharing.
Gigy

The timing is strictly dependent on the biology of your cancer, whether it's fast growing (aggressive) or slow (indolent) can only be determined with time. As long as you're kept under close surveillance most oncologists feel comfortable with waiting.

There are no rules one way or another. In the following quote Dr. West makes a suggestion for a treatment break. The circumstances are different but the idea of being without treatment is the same. "There's a point at which the cancer can't be knocked back down with treatment or the person is too sick from cancer to take tx. The general principle I follow is that if we can’t feasibly be treating for cure, I favor the least toxic approach to control the cancer over the next significant chunk of time (say, several months). If the cancer is indolent enough, the least toxic approach may just be ongoing surveillance with a plan to intervene when it looks more like there’s an actual risk of cancer-related symptoms in the near future, as opposed to giving potentially side-effect inducing chemo that may well be worse than the underlying disease" http://cancergrace.org/topic/no-more-stable/#post-1262955

Yes, I'm Janine

Yes, exactly right. Some cancers can be left untreated for months, even (rarely) a year or more without needing treatment. Others will progress in under two months, and sometimes over just a few weeks. It it's a matter of just 2-3 weeks to clarify what might be the best treatment option, it's typically quite appropriate to seek the best treatment a little later vs. just the most readily available treatment, even if it's not the best. On the other hand, unless someone has a cancer that is known to be slow-growing, waiting more than a month gets into a range for delay that becomes increasingly concerning.

The most important variable, though, is the underlying pace of the cancer and the relative appeal of the later potential option vs. the "bird in the hand".

Good luck.

-Dr. West

Hi Bethw,

Thanks for sharing your experience.

We have been tracking the medi4736 + Tremelimumab study as well (for solid tumors, as I have a family member who has ovarian cancer), though that study is going very slow - they saw some toxicities early on and there is a very long wait list for that trial. Possible reason for toxicities - different dose/schedule and different patient population.

So happy to learn that you are responding so well to the combination. What dose levels are you on right now? (And was it part of the escalation phase or the expansion phase?) Did you experience any side-effects like colitis, etc ( which I understand are primarily from Tremelimumab). Wishing you continued good results

Considering the combination has pd-L1 drug (compared to anti-pd1 drug Ipi in the Nivo/IPI combination which seemed more toxic in the NSCLC population, presented at ASCO this year), many are hoping this will be a relatively more tolerable combination while improving the benefit rate viz. anti-pdl1 agent alone.

I understand Dr. Creelan is running this combination trial along with a few colleagues; and would be very appreciative of his insights on the experience they have had so far.

many thanks in advance

Just in case Dr. Creelan doesn't see your post andy123 I'll let him know you've asked for his input.

To address question of anti-CTLA-4 plus either PD-1 vs. anti-PD-L1:
We do have several of these Phase I trials for lung cancer open at our center for past year or so (eg nivo/ipi and also tremi/medi).

I believe most would agree that this combination concept is more potent. My understanding is that there are several advantages to the combination: for example, based on scant information so far, the responses seem to be independent of PD-L1 status. There also seems to be a higher proportion of responders as well, although still not as high as we want, which is 100%. At the same time, the combinations do seem to have more autoimmune side-effects as well: GI, skin, endocrine, for example. These are usually quite manageable with courses of steroids or hormone supplementation. Nonetheless, in contrast to chemo where almost everyone has some cumulative toxicity, most patients cruise along with few problems. At the end of the day, most patients are wiling to accept a higher risk of these auto-immune side effects, if it means NOT talking about recurrent lung cancer. Hope this helps.

Hi, Andy123--

The "study doctor" for the trial I'm in at Moffitt is Dr. Scott Antonia. It's in the dose escalation phase and my cohort gets 10 mg/kg MEDI4736 + 3 mg/kg tremelimumab. I've not had much in the way of side effects (see below).

I feel fortunate that I just happened to enroll when that MEDI dose was on the table, given that 10mg/kg was chosen for the dose expansion phase of the MEDI4736-only trial for which I was wait-listed at Moffitt.

My scan results last week were good, though not as good as I had hoped. (Give me an inch and I want a mile!) Most of my mets shrunk a bit more (10-17%) but the rate of shrinkage seems to be slowing. A couple mets and my primary tumor were "stable." (Stable is good, stable is good, stable is good...)

One lymph node apparently grew a bit but trial coordinator is chalking that up to measurement error (went from 1.0 x 0.5 cm to 0.8 x 0.7 cm). The radiologist indicated that another similarly-sized lymph node they've been tracking was "difficult to measure."

I did get another piece of what seems like very good news: I've had a bunch of scattered nodules or lesions in both lungs and docs disagree re what they are. Whatever they are, they've all decreased in size!

Maybe my immune system was busy with those :)
_____________________________

Knock on wood: I've only had minor side effects including the usual fatigue (and who knows what that's from -- could be this treatment, prior treatment, the cancer itself, and/or the fact that I'm no spring chicken!) Also a little bit of itching and dermatitis...

The latter seems to be part of a pattern in which my immune system is overreacting a bit to minor insults: e.g., I had a bout of dermatitis in my outer ear which I think stemmed from a mosquito bite (to which I usually have little reaction), and a tiny shallow cut with a clean kitchen knife seemed to call up an armada of white cells!

Interesting (to biology geeks like me)... but definitely not serious!

-- Beth

I should clarify this: Dr. Antonia is the study doctor at Moffitt for the trial I'm in. I don't believe he's in charge of this 4-site trial as a whole.

Clinicaltrials.gov lists a doctor from MedImmune, Joyson J. Karakunnel, MD, as the study director/PI.

Great input Beth! I love it, give me an inch and I want a mile :wink: When I read these results I like to keep in mind that these drugs seem to have more of a rise and fall to their efficacy pattern so your mile is still on the table.
Thanks for helping us bring science and the practice of treating lung cancer a step...or 2 further.
Janine

Hi again Mike,

How are you doing man?

I had a full round of taxotere infusions, and my nodes have not grown. So I was on a chemo break for three months, I had a scan last week - no progress in the nodes again. So, still no reason (i guess) to go back on a chemo plan.

I am still looking for a MEDI4736 and tremelimumab trail....no luck so far. I'm also lookign for and Ipi and Nivo trail for guys like us.

I have no symptoms - eating well, not losing weight. I feel fine actually.

My warm regards,

Bill

Hi Bill,

Great to hear the encouraging scan results, as well as the fact that you feel fine...congratulations!! Thanks for sharing such a positive update.

Good luck on your trial search.

JimC
Forum moderator

Thanks for your kind remarks Jim.

I'm working on a National Barrett's and EC early detection awareness campaign.

I've teamed up with Rhonda Small, President of the Esophageal Cancer Awareness Association, http://www.ecaware.org/, and Dr. Jonathan Aviv of NY, NY.

https://www.youtube.com/watch?v=uBhV5BHCHN4.

I'm a 25 year veteran advertising/communications director, and feel that this campaign will be very effective in getting out the word for early detection for folks at risk. Maybe same some lives.