Are you currently (or have you been) in a Clinical Trial?
Comments
-
Cure-ious,
Thanks for the link. This is the plan we are going to try for now and I'm satisfied with it for the time being. We'll see how it goes. Waiting for the faslodex appointments to start.
0 -
Cure...so it sounds like you agree with the statement...and that CAR-T really is a major long shot based on the way they do it currently....correct?
0 -
It depends, right?, so, for example, those cancers that switched from ER-positive to ER-negative tend to respond much better than conventional ER-negative (or ER-positive) cancers do. Why is that?! It's very possible those cancers are either producing more neo-antigens (weird-o proteins on their surface that attract the immune system and get lots of TILs) and/or they do something to disrupt the immunosuppressive tumor microenvironment. Those folks who got great response from Keytruda-Halaven (Barbara Bigelow) or from CAR-T type of approach (Judy Perkins) were in that category- for those folks the approach as it is currently configured was already life-changing...
For traditional ER-positive or ER-negative, the answer to all kind of immune based therapy will be to add on something that is making the cancer more exposed and/or express more neo-antigens (DNA repair inhibitor, CDK12 inhibitor, etc). These things are in trials and everyone weighs waiting for the more information on which ones work best, versus how soon do they need to give it a try and just take their best shot?
0 -
Question Cure-ious. I am in a place where biopsies and genomic testing are a bit tougher to get approval for (although I will once again be pushing). Do you have a sense of how common it is for things to flip when we become resistant to hormone therapy? In other words, how likely is it that I am now ER negative given that I no longer seem to be responding to estrogen based therapies?
I feel like this is a bit of a dumb question but I am trying to get my ducks in a row for a precious in-person appointment with my MO who has been on sabbatical for six months. I need to choose my battles carefully to make sure I get the most of this opportunity and want to make sure I highlight the best options for exploration. Clinical trials may not be an option as there are limited opportunities here but it all factors into the discussion.Thanks!
0 -
Thank you Cure.
So i forgot to tell you guys....but during my appt with my MO yesterday after I asked her if I only really have 2 chemos left (and she said yes) she told me that my cancer center is doing this thing called PRODIOMEX (not sure of the spelling) but what it does is takes a sample from you biospy (mine was from Nov) and it looks at the protiens made by the genes....some protiens show up that werent on the gene testing... so she is going to try to get them to test my sample....
0 -
Nicole,
That sounds interesting. So what's the theory behind it -- that that might suggest other treatments? or trials?
0 -
Yes...to be able to target something specifically....
0 -
I don't think I've written here but I'm happy that you all are here. I recently flipped to triple negative and am about to start Xeloda. My MO is strongly encouraging this trial for me, as of this morning. I just had an appointment yesterday and made the plan for Xeloda. If you have a chance to read the details, I'd appreciate your take on it. My take was no thanks. Tons of “common" and awful sounding side effects, it's only in phase one which to me means no benefits to go on to make me want to do it. Some weeks are 3 days at the hospital for infusion and monitoring early on. Maybe those aren't really negatives to others. I would be part of Group F which allows for no prior chemo. So now or never
Sorry, I’m not able to attach the local description I received. It had a lot more details that were helpful to know but overwhelmed me with how much was involved to be in this trial.https://clinicaltrials.gov/ct2/show/NCT01969643
0 -
Hey Rosie,
I'm surprised to see a Phase I trial that doesn't allow prior chemo. Usually, Phase I trials are less strict because they are riskier so it's harder to find people willing to try them. Particularly weird to ask for that from TN women who have few options other than chemo. No wonder they have been working to recruit for the trial for eight years!
Looks like my MO is running the trial at UCSF. I will ask her about it when I see her next, which may be awhile since I just saw her.
Hugs, Susan
0 -
Hi Susan, Group F is the only one requiring triple neg and no chemo. A-E are for various subtypes and treatments, but most of those are not accepting new patients. Maybe I’m their typical Group F person—flipped to TN after targeted therapy for some years?
0 -
Hi Sadie-Server!! (How is Sadie doing?!) Can you post a short list of the order in which you have gotten treatments? Hard to know how long or not since you tried endocrine therapy. It's rare that the cancer flips from ER-positive to ER-negative, instead the ER usually remains there in the cell but the cancer no longer depends on it for growing. But sometimes it still does, and the only way we could know that in advance would be doing one of those FES-PET scans, so you might ask if that is an option. And then, hopefully they are doing a new biopsy and/or new genetic testing to try to see why the cancer is progressing, more common reasons are that PI3KCA kinase has gotten activated (either by PI3KCA mutation itself, or indirectly turned on by one of several growth hormone pathways); or HER2 gene has gotten turned or (or less commonly mutated, to become active), either of which is a (relatively) good thing because then you could take advantage of the treatments they are using for HER2-low MBC; or mutation of estrogen receptor itself (so-called ESR1 mutation), which can be treated by the new SERDs in clinical trials, or the ARV-471 PROTAC that degrades the estrogen receptor that Alabama Dee used. If the cancer mutated to ER-negative status, the biopsy would reveal that, and the strongest indicator for that would be one of the newer immunotherapy (checkpoint inhibitor) combo trials.
The data coming out of the SERD trials is very impressive and all of those trials are in MBC patients who progressed after endocrine therapy. These drugs are a lot stronger than the I-F, and indeed some trials like ARV-471 say they are seeing responses in people who also progressed from a SERD trial! Sometimes, it makes sense to take a break from endocrine therapy to try other drugs like PARPi or immunotherapy, and while there is no selective pressure on the cancer to not use estrogen, it returns to using the estrogen receptor to grow, and hence is sensitive again to the endocrine agents.
What hospitals would you be able to go to for a clinical trial?
0 -
Nicole, I think you are referring to proteomics, which is a generic terms used to describe a test or evaluation that looks directly at what mutant or over/under-expressed proteins might be present in the cancer cell, as opposed to what DNA mutations the cancer has, or what RNAs the cancer expressed. The issue is whether the test is looking at are the state of the DNA, or the RNAs, or the proteins that are in the cancer cell.
0 -
Hi Cure-ious! Sadie is doing well. Becoming bossier by the day and showing her age a bit (she will be 10 in June) but still playful and keeping me moving.
My bio is pretty accurate (it’s starting to get a bit embarrassing - somewhat like the “volume 3” of my file at the Cancer Agency - so I have been wondering if I should simplify it). Started out on Taxol which didn’t help the pleural effusion. Next Arimidex and added in Ibrance. Couldn’t tolerate the Ibrance (hemoglobin tanked) then the AI failed. On to Xeloda for four cycles but not sure it was working so switched to Faslodex. Had a good run on that, layering in Verzenio for 14 months before liver mets appeared. This is the point where my MO decided I was endocrine resistant. Took Xeloda with good success but MO concerned about marrow toxicity so we are keeping it in our back pocket as something to return to. Navelbine - no response and now on Eribulin (response TBD).
While I think the world of my MO, he has remained resistant to the idea of biopsies and genomic testing. I suspect part of the problem may be the challenges of getting approval in our system, particularly now that Covid is leading to cancellation of procedures. He is also less convinced of the efficacy of genomic testing as his experience is that the treatments that it points to are things he would do regardless. However, I am equally unconvinced that this remains the case given how quickly things are moving now.
The hospital question is also a tricky one. Most likely it would have to be a trial available at BC Cancer in Vancouver although travel within Canada is not completely out of the question depending on the parameters of the trial. The do carry out trials at my local centre but the are less abundant. Your recent post was the first time I had heard of an FES-PET so will need to do some research to see if this is available in Vancouver.
Thanks for the explanation on the switch to triple negative. I’ve wondered about Piqray but wasn’t sure if it would be effective given that Faslodex and I have already had a three year dance and I know that’s what it is typically paired with. I’ve been watching the new SERDS but don’t think they have made their way north of the 49th parallel yet. 😊
Thanks again!
0 -
I shared this with Cure-ious... and this is sort of in conjunction with Pionyr's PY314 TREM2 study. They are doing a TREM1 Phase 1 study using PY159. I got approved (but declined due to vacation plans and the co-hort I would be in). But I thought this might be of interest to anyone out there.
https://clinicaltrials.gov/ct2/show/NCT04682431
Here's a video:
https://www.vjoncology.com/video/efdujru4aww-pionyr-immunotherapeutics-overview-and-the-potential-of-py159-for-the-treatment-of-solid-tumors/0 -
Thanks for bringing that trial up, Holli, I'd not heard about it- both the TREM1 and TREM2 are markers on macrophages that are shielding the tumor from the immune system, so the combination of either with Keytruda (or another checkpoint inhibitor) could be a game-changer, because the treatment would then both activate the immune system and expose the cancer to attack. TREM1 is on more kinds of immune cells than TREM2 and they have different activities so will be interesting to see how the two trials do- both of them use monoclonal antibodies to attack the TREM1 or TREM2, so those are more specific inhibitors than a targeted drug, reduces the chances of collateral damage.
What's unusual about these trials are they do accept ER-positive MBC patients, without a need for PDL1 expression or high tumor mutation burden, most other immunotherapy trials are just for TNBC. Another thing about them is its designed with a helluva lot of patients, relative to most phase one trials, that's costly and suggests they think it will work. The trial will test whether the tumor has TREM1/2 expression which is required, however most cancers do. These drugs come from a small company, Pionyr, but Gilead has bought 49% with an option to buy them outright depending on the results of these Phase 1b studies.
0 -
Sadiesservant, Indeed there's nothing compelling in the Vancouver clinical trials at the moment, it seems like it would be more helpful to try to get information about what is driving the cancer. Piqray with Faslodex would definitely be a good option IF the cancer has a PI3KCA mutation, which you would learn about from the genetic testing. In that case it doesn't matter that you progressed on Faslodex beforehand, the Piqray would turn off the PI3KCA and make the cancer depend on estrogen again, and it would become responsive to Faslodex again. There are quite a few other ways the cancer can turn on PI3KCA, but we don't have biomarkers for them, so for that reason some people respond well to Piqray even without a PI3KCA mutation. Hopefully soon they can combine drugs like Piqray with a SERD, instead of Faslodex.
Another thing you would like to know is if there is any Her2 expression or mutants, which would make the cancer Her2-low (this is one of the more common ways that cancers become resistant to Faslodex) because then you could go onto Enhertu or the other drugs they use for Her2-positive cancers. The FES-PET scan could be used to determine if the cancer is or is not sensitive to estrogen receptor, but its reasonable right now to assume it is not, and try to figure out why not, ie, is it growing on PI3KCA kinase or Her2, etc...
0 -
Cure-ious,
Am I reading your most recent message to Sadiesserant correctly -- that if you have HER2mutant cancer it can (will?) be resistant to faslodex? I am about to re-embark on faslodex coupled with neratinib. Is this an automatic exercise in futility?
Thanks.
0 -
BevJen, Nope, you're fine....Her2 activation is one way that leads to resistance to faslodex (ie, cancer is growing on Her2 pathway rather than the estrogen pathway), but in your case you are taking a drug that inhibits the Her2 (Neratinib), which then makes the cancer go back to growing on estrogen, so that's why they add back the faslodex to block that part. Its the central strategy of many combination therapies...
0 -
Wow, here is some GREAT news!!
An update on the Rosenberg TILs trial, many of you know of this trial, this is the one that cured Judy Perkins..
They take your lymphocytes and engineer them to go after one or more neoantigens that they find to be present on your specific cancer (in Judy's case they found four unique cancer-specific neoantigens to go after)- this approach is massively expensive cuz they have to look specifically at the proteins your individual cancer expresses
Anyway, they now have added two more women who maybe cured- one is five years out, the other 3.5 years out, on no drugs since taking the therapy- amazing!!
https://www.nih.gov/news-events/news-releases/nih-...
0 -
Cure-ious,
Thanks for that explanation. Phew. Nothing like starting a different treatment and wondering right out of the box if it will work.
0 -
Cure - there was an article today in the Guardian about the first CAR-T recipients and 10 years on they remain cancer-free. The article goes on to explain how it works for blood cancers and they are trying to figure out how to get it to work for solid tumor types (see: all the research posted on here!). I know we all have to hope for something, but it really does feel like research is on the cusp of some significant breakthroughs.
0 -
Cureious...I was postive that actual trial is not even available any more the one that cured Judy and those women? Is it? Do you know the trial number?
0 -
Sondra, Yes, I saw that, two cures (ten years out from treatment) for leukemia by using CAR-T!!! There is nothing like this kind of success to drive further innovation. For Multiple Myeloma (another blood cancer, which is a bit easier to treat because its not hidden from immune system and it has a cell surface protein that can be targeted well)- there are at least two CAR-T approaches that were recently approved by FDA; in those clinical trials, about 1/3 of the people were (apparently) outright cured of their cancer by the CAR-T, despite having been heavily treated with standard procedures, including with ADCs to the surface antigen, and with nothing good left for them to try...
0 -
Also wanted to mention a phase two trial opened in 2020 for an ADC (antibody-directed chemo) targeted to ROR1; this protein is especially high in lobular cancers, although it is open to all MBC except Her2-positive. Available only in Texas (MD Anderson), Florida & New Jersey. Primary data completion expected in July of next year.
https://clinicaltrials.gov/ct2/show/NCT04504916
Here is a different version, in phase one, but only for TNBC and only at the Hutch in Seattle: https://clinicaltrials.gov/ct2/show/NCT02706392
And another one, for solid tumors, at Sarah Cannon and MD Anderson: https://clinicaltrials.gov/ct2/show/NCT04441099?te...
0 -
Cure-ious,
Would love to be on the Rosenberg NIH trial but it has been suspended. A couple of years ago he said he was trying a new direction and hoped that some private companies would develop CAR-T therapies.
https://www.onclive.com/view/t-cell-immunotherapy-pioneer-seeks-new-direction-for-solid-tumors
Excited about the new ROR1 ADCs. So many new drugs for MBC. Hopefully, they will be available soon.
Just got my second infusion of ARX-788. Feeling tired because of the Benadryl but otherwise good!
Hugs, Susan
0 -
Hi, Any information on using anti-hormonals along with Taxol? I quit Ibrance/faslodex(worked for 3/12 years) after it obviously stopped working (needed surgery). After that I was on solo exemestane for 2 months but obviously getting worse so started Xeloda and moved on to Taxol). I'm Her2 neg, have lobular mets in peritoneum so no solid tumor to test. In the future Can people go back to CDK inhibitors+ SERDS/SERMS since they are testing newer ones? Just wondering where my next "leap" will be. Thanks
0 -
Nina, Of course you can(!), the SERD trials are all full of people who progressed after I-F and AIs, many also having had chemo. Best to get a second opinion at a cancer center that runs clinical trials. And also biopsy/genetic testing of the cancer to try to understand why it has progressed, what is driving the growth. With SERDs you could add CDK4,6i, maybe the newer CDK2,4,6i, Piqray, Her2 inhibitors etc. And if you go for chemo, the newer ADS have a much longer PFS than traditional chemo. There are a lot of promising drugs out there but have to get into clinical trials system to access them
0 -
Rosie, Like Nicole, your cancer moved from ER-positive to ER-negative, and studies on that subtype have shown it is more responsive to checkpoint inhibitor immunotherapy than any other kind of MBC.
Although it is in fewer locations, they have now started a version of your trial that includes the SGN-LIV1A ADC and Keytruda. The trial requires no prior chemo.
https://clinicaltrials.gov/ct2/show/NCT03310957#co...
Whether or not you could get the Keytruda added, its a good sign they are expanding the treatment.
0 -
Hope tweeted this link and it raises a lot of questions about diagnosing HER2 low patients:
https://jamanetwork.com/journals/jamaoncology/article-abstract/2788567
HER2 2+ ISH doesn't seem to be in question.
0 -
Cure-ious, I try to read and educate myself on possible treatments but I have so much I don’t know. Thanks for being here. I’ll be going ahead with the trial assuming no surprises pop up before Friday.
0
