Update on MGD007 Trial – New Sites Open!

[DK37]

As many of you know, I am a big fan of the strategy employed by the experimental drug MGD007. It physically drags immune T-cells into close proximity to cancer cells displaying the gpA33 marker. About 95% of CRC (including CRC stem cells) are gpA33+. It is a brute force type of immunotherapy but unfortunately CRC has not responded to more subtle forms of immunotherapy (yet).

My main concern revolves around toxicity. Normal GI cells also display gpA33 – which could likely cause some GI-toxicity or colitis. A second part of my concern is like any strong immunotherapy, there is a chance of cytokine release syndrome (CRS) which can be very serious. https://en.wikipedia.org/wiki/Cytokine_release_syndrome Related to this, our own Belle was patient #1 on this trial and she experienced very bad toxicity (GI and potentially CRS as well). I have been told that of the 6 patients in dose cohort #1, only 1/6 patients developed such major tox (Belle). They are now dosing the next higher dose level. Until more patients get dosed, we can’t know if Belle was an extreme outlier in terms of tox or not – hopefully at least some of the next round of patients will blog their experiences on CC – both in terms of efficacy and tox.

The GI toxicity Belle had “may” have been an indirect measure that the drug was attacking her tumors as well? Sort of like the cetuximab rash/tumor efficacy correlation since in both cases, tox could be due to successfully hitting the target (EGFR+ or gpA33+) in a tissue outside the tumor, implying that the (EGFR+ or gpA33+) tumor is being hit too. For Belle’s tox reasons I remain cautious about this trial until we hear back how the next round of patients does but if I were later Stage IV, it would be in the top tier of trials I would be considering with my MD.

I mostly wanted to post this update today because they have dramatically increased the number of trial sites. This “could” indicate internal optimism that things are looking good. That potentially incorrect conjecture aside, having more sites open will generate data much faster (good or bad) which is great news for the patient community!

-DK

https://clinicaltrials.gov/ct2/show/NCT ... 007&rank=1

Current expanded sites pasted below:

United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21205
Contact: Ellen Lilly-Foreman, RN, OCN 443-287-4961 lillyel@jhmi.edu
Contact: Thomas Brown 410-502-5328 tbrown55@jhmi.edu
Principal Investigator: Daniel Laheru, MD

United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Margaret Carey 617-632-5575 MargaretM_Carey@DFCI.HARVARD.EDU
Principal Investigator: David P Ryan, MD

Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Susan Sheehan, RN 617-724-4000 Ssheehan1@mgh.harvard.edu
Principal Investigator: David P Ryan, MD

United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Anthony Amara 919-668-1861 anthony.amara@dm.duke.edu.......
Principal Investigator: Herbert Hurwitz, MD

Carolina Biooncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Ashley McClain 704-947-6599 ext 117 amcclain@carolinabiooncology.org
Principal Investigator: John Powderly, MD

United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Yue-yun To, RN 503-215-2855 yue-yun.to@providence.org.......
Principal Investigator: Todd Crocenzi, MD

[vilca11]

Thanks for posting, DK! In the absence of Maia, we would be in the dark without you and Joe777777, very important to know what to keep an eye on and try to hang in until the most promising thing is available for so many of us. Your input is especially priceless, since you are an industry insider and can "feel" anything new that pups up incomparably much better than anyone else....So, again, many thanks for your input/contributions to this forum, dear DK!

[pukalania]

Thank you DK for posting this

[bitchslapped]

Yes, thanks for updating, especially posting the effects Belle experienced as some may not be aware.

[lpas]

Thanks so much, DK. What concerns me about Belle's experience is that, in addition to the horrible side effects, it didn't seem as though she benefited much from the treatment. Have you heard if any of the other first 6 patients showed any improvement (or at least a halt in progression)?

As an FYI, it looks like Colondar model and occasional poster, Lindsey Motley, is also attempting this trial. Some may remember that Lindsey was diagnosed at age 26, while 17 weeks pregnant. See her discussion here on Caring Bridge:

http://www.caringbridge.org/visit/lindseymotley

[janderson]

Thank you so much for posting and giving your scientific insight.

[peanut_8]

Thanks so much for posting and keeping us educated, DK.

We are truly lucky to have you.

peanut

[DK37]

Thanks so much, DK. What concerns me about Belle's experience is that, in addition to the horrible side effects, it didn't seem as though she benefited much from the treatment. Have you heard if any of the other first 6 patients showed any improvement (or at least a halt in progression)?

As an FYI, it looks like Colondar model and occasional poster, Lindsey Motley, is also attempting this trial. Some may remember that Lindsey was diagnosed at age 26, while 17 weeks pregnant. See her discussion here on Caring Bridge:

http://www.caringbridge.org/visit/lindseymotley

Hi lpas,

Please correct me if my memory is faulty but my recollection is that Belle did not have too many infusions because her side effects/toxicity were so bad she had to stop the trial. I don't remember her disclosing any scan results, but once again my memory may be wrong. Regardless, if she did only get a small number of infusions at the lowest first dose tested, it is probably too early to judge the potential efficacy of the drug based upon her experience.

This is especially true in regards to immunotherapies, which often require longer dosing to see efficacy on scans than is normally seen in older chemo/targeted therapy type regimens. I believe in some of the earliest checkpoint inhibitor trials they realized that they missed out on noticing some efficacy if they initially relied on the first scan to make a preliminary judgment, efficacy sometimes only became clear later on in the next set of scans. Immunotherapies can also sometimes show "pseudo progression" on first scans due to infiltration of immune cells into the tumor making the tumors appear to get larger. Aside from lower tox, I have not heard word on efficacy in the other 5 first cohort patients - either good news or bad news,

Purely from a "scientific guess" perspective, I like MGD007 because it is a logical approach and because there is successful proof of principle (in humans!) of the same strategy being used by Amgen's FDA-approved drug "Blincyto" against the "ALL" blood cancer. Blincyto uses a different cell marker in order to drive T-cells toward the "ALL" cell type, but strategically they use the same process as MGD007, MGD007 just switches to a CRC cell marker "gpA33". Because of that, as a scientific guess, I think MGD007 has a great chance of efficacy (better than usual) - ***IF*** on-target toxicity allows them to dose high enough/long enough, since normal GI cells also have the gpA33 marker. So in the end, I am most worried about toxicity screwing up MGD007's chances. I assume there will probably be GI tox which will need to be managed well & long enough to allow the drug to do its job & eradicate the tumor.

Hope that makes sense - but all of this is just my personal guesses at this point. I'm waiting for clinical data like everyone else. Yes, it sounds like Lindsey Motley may be blogging her MGD007 experiences shortly - that could be very useful information for all of us to read. She is an AMAZING woman - I sincerely hope the trial works for her!!

-DK

[jgall]

And my DH had a good call with the trial people at one of the new sites, so I think he may also be jumping on this trial in the near future. I will definitely post his experiences here as well as our caringbridge when we get there. Thanks for your help, DK, in assisting us over the last couple months. You've been our angel and we can't thank you enough.

Julia

[lpas]

Thanks, DK. That explanation makes a lot of sense. Here's hoping the toxicities can be managed and we see some good results for this next round. And an extra special thanks for keeping us so well-informed (as always!).

Good luck to you too, Julia and Chris. Will be swinging lots of chickens for you!

[DK37]

I'm happy to help give a "research scientist's" viewpoint, so that fellow patients can have better informed medical decision discussions with their MD's. I sometimes joke that CC feels like Gilligan's Island and I've been cast as the Professor haha.

But in all seriousness, I too am only making best guesses based upon pre-clinical data and logic - with these early trial drugs, at the end of the day no one has a crystal ball, the trial will tell the data. As of right now, MGD007 showed very serious tox (Belle) in 1/6 = 17% of patients. That is the data currently known. Everything else is just high efficacy in animal models, a strong logical basis and a proof of principle of the strategy in a different type of cancer as our current guiding lights. I am so grateful to trial participants like Belle, Lindsey, Chris & many others in the CC who trail blaze for the rest of us... All incredible heroes in my book.

-DK

[lilacbreastedroller]

NIfty. They ought to invent some kind of special probiotic yogurt patients can eat that would coat the inside of the colon and protect it, if that would even work since the yogurt would be digested in the stomach... There needs to be something that wouldn't protect the cancer cells, only the healthy ones. My vote is something benign, ingestible, and strawberry flavored!

- Karin

[gator.girl]

Thanks DK! My docs all think I am so smart but it's all because of you lol!!!
Maybe I should start a new thread but was wondering what you thought of the new approved drug ramucirumab to use with folfiri

http://www.drugs.com/newdrugs/fda-appro ... -4206.html

Not sure how to tag people here in cc? So I thought I'd put here since you seem to follow this thread... But am happy to start a new thread...


Thanks

Ginger from Gilligan's island lol

[skypup]

I claim Gilligan!

[DK37]

was wondering what you thought of the new approved drug ramucirumab to use with folfiri

http://www.drugs.com/newdrugs/fda-appro ... -4206.html

D

Hi Gator.girl - To my eyes it is an incremental advance rather than a major breakthrough - but incremental advances do slowly add up... Nice to have one more approved therapy to try in the arsenal until the inevitable breakthroughs do arrive Works similarly in KRAS-wt and KRAS-mut, similar class of drug as Avastin.

-DK