Agios to Present Clinical Data from Ongoing AG-120 Phase 1 Trial

Boston guy-

Our fingers are crossed for you too!

Best wishes,
Catherine

Latest results are very mixed today. My mother is feeling about the same at the moment, with stable weight.

Her alk phos is stable at 321, down from the peak of ~600, and her CEA has decreased from 11 to 5. Her WBC is also down from 14 to 8.6. Other LFTs are essentially normal. Bilirubin is stable

The one bad news is that her CA 19-9 has increased from ~1000 on 6/10 to about 17,000 as of today (7/12). The oncologists are not sure what to make of it given the dramatic improvement she had in her other labs and the fact that she clinically appears stable.

We are planning to repeat labs and do the CT scan in 2 weeks, which will be earlier than initially scheduled (was supposed to be in 4 weeks).

Given the significant improvement in her other labs, we’re keeping our fingers crossed that the CA 19-9 increase is not just due to tumor progression. She doesn’t have signs of biliary obstruction or anything else obvious to cause the increase, but CA 19-9 is not the most reliable tumor marker.

I will give an update when we get it in a couple weeks.

Steven, so sorry to hear that things have been rough for your mother. If you are unable to get approval for other clinical trials it might be reasonable to ask your mother’s oncologist about off-label dasatinib given the positive preliminary data out of MGH regarding it’s use in IDH-1 mutations. It is an oral medication with minimal side effects. Keytruda generally has less efficacy in patient’s without mismatch mutations, so it might be reasonable to ask about dasatinib first. Since the MGH dasatinib trial may already be closed it seems reasonable to at least ask about using it off-label.

Regarding an update on own mother, she has only been on AG-120 for about one week but surprisingly her LFTs have come down considerably, with her alk phos decreasing from ~600 to ~350, normalization of her bilirubin and transaminases (AST/ALT), and otherwise normal labs.

Hard to say what the lab results mean over such a short time, but it is nice to see the labs finally have some improvement. I’ll be sure to provide more updates as we go along.

Just to provide an update on my mom’s situation, we have had quite a few gut wrenching weeks trying to get her started on the “Selumetinib in Combination With MEDI4736” trial at the local participating facility (Rutgers/New Jersey Cancer Institute) — https://clinicaltrials.gov/ct2/show/NCT … amp;rank=2. Mom was all set to get started last Tuesday 6-14 with Dr. Ann Silk’s team at Rutgers (the trial can be started on Tuesdays only). She had a fever the Weds prior and was hospitalized at Morristown Memorial with possibly pneumonia, so they gave her antibiotic as a precaution. When the trial team at Rutgers was informed, they said she could not start on the trial with a possible infection and/or because she was on antibiotics so soon before the start date. The Morristown team immediately took her off of the antibiotics since she did not necessarily have an infection, but it caused us to miss that Tuesday window. We then went back down to Rutgers this past Friday (6-17) and had another battery of tests that all came back good and clear, so she was set to start this morning (Tuesday 6-21) on the trial and we were all hopeful.

Rutgers then called yesterday to tell us they needed to re-do her echocardiogram within 14 day window of start date as a trial protocol. We then got the horrible news that they unexpectedly found fluid around the heart and they are telling us that, with that, she is “too sick” to be on the trial. We have her back at Morristown to deal with the fluids and they are putting in drains in both the lungs and heart, and possibly the belly as well to be able to drain the accumulating fluids. Unfortunately, by gearing up for the Rutgers trial and trusting all of our proverbial eggs in that basket, we have now not been able to treat the cancer for over six weeks (due to wash out and eligibility requirements). The last treatment that provided any kind of positive result was the Agios-120 trial, that unfortunately just was not positive enough for them to allow us to continue on that trial (she almost certainly would be in much better condition today if she were permitted to stay on that trial).

We are now left scrambling to see if there is any way she may be able to re-qualify for the trial, or otherwise start chemo as soon as possible once the incisions heal and continue our application for Keytruda, which we submitted last week to the Merck Access Program under the care of Dr. Michael Scola at Morristown Memorial; or otherwise go back to square one of exploring whether there are any other promising alternatives out there that she can get started on rather immediately.

We all realize (with maybe just a little denial) what the fluid and related symptoms mean with respect to the advanced stage of her cancer, but she is a fighter and not ready to give up, nor am I or anyone else in my family.

If anyone has any suggestions with respect to expediting the Merck Access Program process or otherwise, I would certainly appreciate anything you can share.

Thanks to all for reading this and for all the help and support over the past year. This community has been such a tremendous blessing and source of support.

Best,
Steven

Thank you for the replies. Despite being a physician and dealing with these things all the time this has been quite difficult for me. My sister and I lost our father just a few years ago to thymic carcinoma, an even rarer cancer. I was in my 20s then, and only 31 now. My dad was 60 and my mom now 66. They were both healthy right up to the moment of diagnosis and nobody else in their immediate or extended families with cancer. Everybody else has lived to 90+. Too young for all this nonsense…

Thank you for looking into it. I will contact the NCI MATCH team about her case. I think it certainly seems like dasatinib should be the next option if AG-120 were to not work (I hope it does work though). I also shot an email to the PI of the dasatinib trial at MGH to see if he has any thoughts (I’m not sure if that’s who you already reached out to…sorry if I’m repeating your work).

I have to say, I never would have thought that a discussion board would be a source of information for me as a physician myself, but this community has been incredibly informative and helpful. Thank you again for all that you have done.

Thank you!

Hi all,

This is my first post here. Thank you for all the incredible efforts of everybody here to keep the community informed of developments in the treatment of CCA.

I am a physician in Boston myself, but generally there is not a ton of exposure to CCA, and particularly not to any of the cutting edge treatments that occur mostly in trials. I mostly see patients that have the complications of CCA, such as cholangitis, etc. This forum has been helpful in my research.

My mother was diagnosed with intra-hepatic CCA in 12/2016 and has since progressed steadily through gem/cis and now FOLFOX. She does not have any extra-hepatic mets, but feels very unwell from the increasing tumor burden in her liver.

We are going to be starting the AG-120 trial on Wednesday after she has the repeat liver biopsy (ugh, I can’t believe she has to have three biopsies for this). I hope that it works. The dose will be 500mg per day, which I think is what was determined to be the maximum tolerable dose.

Also, her genetic panel came back showing mutations in IDH-1 and also ABL-1. I know that dasatinib has been shown to work on some IDH-1 mutant CCAs, but it is interesting because dasatinib is also used primarily for CML when there is a mutation in BCR-ABL.

I have been unable to find anything about the utility of dasatinib in patients with IDH-1 and ABL-1, or if dasatinib has any value when an ABL-1 mutation is present in a solid tumor.

Has anybody come across a situation like this? We are certainly going to try the AG-120 trial, but it would be good to know if there is evidence to suggest we should actually be moving forward with dasatinib as our next choice.

Thank you in advance!

– bostonguy