Are you currently (or have you been) in a Clinical Trial?
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@cure-ious Thank you for the brain mets trial info. A trial using TDM1 with tucatanib is recommended for my consideration if I have a significant progression on Enhertu.
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@cure-ious, @dulcea. Thank you for this information on the new molecules regarding the PIK3CA mutation.
I'm on my 23rd week of Truqap (yes, very tolerable). It's good to read you and know that new treatment options are being studied for this mutation.
I do not have the sufficient knowledge you have but your messages are very interesting and enriching.0 -
@soldanella I am very grateful too for all the smart ladies -like @cure-ious -on these boards! I'm glad to share whatever I can to help other people too, but I can't imagine it's much.
I am very glad to hear that you have had positive results with Truqap. I hope I do too for a long time.
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We are routing for you on Truqap @dulcea ! Hugs to All here!
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Thank you @moderators ! Me too!
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Hi all, I just read this very interesting article .
Cracking the code of DNA circles in cancer: Scientists uncover potential therapy
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Thanks, rlschaller, very interesting- hoping we will see targeted treatments for little circular DNAs (as well as the microRNA-10b, which came up earlier) in cancer cells…
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Cure-ious
This link is not for a trial, but the development may be useful in other ways for MBC patients.
Seven nuclear bone scans over the past 2.5 years have shown a "hot spot" at my calvarium without a lesion. Wondering if this may be the reason.
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How very interesting, Eleanora!
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Okay, so I have my first set of scans from the Bria-IMT vaccine trial. It's not great, not horrible. Bottom line is my RECIST score was 25% and anything over 20% is considered progression, so I'm moving to a different cohort of the trial and adding Retifanlimab to the regimen. It is a PD-L1 inhibitor. My PD-L1 is negative, but the PA said that in combination with the vaccine even with a negative score they have had some patients respond.
I didn't have the scan in my hands when I agreed to go to the different cohort, and now I'm not so sure. She said that compared to what she sees for liver mets on a daily basis, mine is not bad at all, and I have 'room to grow' (my words not hers) so I can afford to stay on this one a bit longer to see if it works with the additional drug. I'm worried though if I wait to jump to a different trial, that if I grow another 25%, that I won't have more room to grow in a different trial or two. Doesn't it make more sense to jump from the sinking ship now instead of trying to plug the holes?
I did ask about that, and she said I could afford to wait, that my tumors were small. But I'm worried if the growth increases any faster, I won't have a chance for another trial. Maybe I'm being paranoid.
She didn't seem overly concerned, but I wonder if her loyalty lies with my health or with the sponsor's complete study data. That's a horribly cynical thing to think, but after seeing this, I don't understand the logic. I'm confident my regular oncologist's priority is keeping me alive, I'm not as confident in their motives.
They did put me on the wait list for TTX-MC138. Not sure if I'll get into the trial, but my next set of scans is six weeks away. I have a feeling that I will jump if that one opens up. Not super confident in this vaccine for me and my type of cancer. If in six weeks if my numbers keep going up, then I'll jump to whatever's open.
That's the update!!
CBL
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Thank you for the update @cblaurenceauthor it's good that you are asking questions and planning ahead. We are thinking of you and we're here to support you however we can ♥️ The Mods
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Thanks for the update, CBL! I am glad they give some additional information on the liver, because of course it always sounds so alarming. But mets grow and shrink and I guess the bottom line for the MOs, as with mets in other locations, is whether there are effective treatments that can handle them? Where are you being treated? I would trust the evaluations in a place that sees lots of patients, and people usually do have to have soft tissue ("measurable") mets to be in a clinical trial, so the PFS should be representative of people in a situation similar to you.
PDL1 positive or negative is not so meaningful a marker for checkpoint inhibitors, meaning it is a promising sign if it is positive but in many trials PDL1 negative cancers also do respond, although not often for ER-positive MBC. But this is different because you are trying it in the context of the vaccine, so do they give any info about other people responding in the trial?. Do you have any other indicators, for example did they do a liver biopsy and look for a tumor mutation burden there, which can be different from what they pick up in the Guardant blood biopsy.And did they do genomic testing specifically for the liver?
And I have read there are scans they can do shortly after trying the PDL1i that give an indication of whether it might be working, so I wonder how they would monitor it. I hope to get some PDL1 at some point, though MBC often does not respond it is combinations that can make the difference, and its an opportunity to see if the vaccine is working, or maybe just starting in to work, can a general boost to immune system help? Also, it is not uncommon for checkpoint inhibitors to give an overall survival benefit even if they don't give a PFS benefit in a trial and I guess that would be because they might make subsequent therapies all work a bit better. What do they say are risks or side effects with this retifanlimab?
PS I wonder if subsequent treatments that include other immunotherapy drugs (CTLA-4 or LAG-3) would have a cumulative effect on the PDL1 you will have already had?
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Hi @cure-ious
I'm at Mary Crowley Cancer Research Center in Dallas. I am ER-positive (PR-) with negative PDL1, so I'm not holding out too much hope.
As for monitoring, there really won't be much time to do bloodwork before my next set of scans. I'll have my first treatment on December 3, post-new-treatment bloodwork and 2nd treatment on Dec 23 and scans on Dec 27, so only 1 real treatment to see if it will work. That won't give it a chance really, but if my numbers are still going up, I'll move to something else ASAP. I'll give it another six weeks, but not twelve if it's still growing.
Yes, she did say that in combination with the vaccine, the PDL1 inhibitor might work, and I'm glad to hear you confirm. She didn't give me numbers, but said they'd had patients who it did work for. My TMB is 5, so very low, according to a liver biopsy. I have no other targets—no PIK3CA, no HER2, no nothing. Ugh.
I'm not sure about side effects yet, but I imagine it's the same as Keytruda (bone pain, diarrhea, etc.).
There is another vaccine trial at the facility that injects a virus either into the tumor or by IV (VET3-TG1). I'm not against trying it if push comes to shove, but there are others I'd try first since I don't know if immunology is the best course for me.
This facility also has an Aurora A (JAB 24-85), or TTXMC-138 (the one I really want), CDK2i (BG-68501), an ADC (AMT 116), or a CDK 12/13 (CT 7439) or a MDM2 degrader (KT-253) that I am eligible for. The problem is finding a slot when I need it, of course, but my name is already on the TTX waitlist. That one could be a while since they just started the second cohort and will need to get a third cohort approved, and I have no idea how long the list is.
So I will try to enjoy the holidays (I hate the holidays, but I'll try, haha) And wait until January 2nd to freak out about joining another trial. I'll be back with another update and probably a lot of questions about which way to go if TTX isn't open yet!
CBL
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CBL You are very lucky your cancer center is offering all these trials; I’ve had my eye on the AURKA one for years, and I would kill to be in the TTX wait list. My cancer center has NO trials of interest to HR+ and I cannot go out of state because I am on Medicaid (not Medicare). I understand that you’re freaking out about your liver mets but you are in a really good place as far as location goes.
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Hi @luce
Yes, I'm very very lucky—I hope I don't sound whiny and ungrateful—just scared. How frustrating for you not to have access to trials that could help. I hope your center picks something up soon for you to try. Mine just picked up a bunch, so maybe there will be a year-end rush of opening trials.
CBL
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CBL I didn’t mean to imply you were whiny. And none of us is actually lucky, of course. just a little but envious of the trial options you have, or might have. Someone there is really picking them well, with much consideration for HR+.
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CBL, Yeah, wow, multiple new trials!! So there is this great list but then these hoops of eligibility and whether there are open slots that keep you jumping. One thing I would add is that inhibiting CDK12 is highly detrimental to cancer cells and makes them very susceptible to immunotherapy, so if your top picks aren't available and you went on that trial, it could do its thing but also add on to the prior vaccine-Keytruda combo.
A recent study showed that anti-inflammatory drugs like Celebrex can help with drug delivery to the liver (liver mets are inflammatory, no surprise) and also NSAIDs synergize with checkpoint inhibitors (the first comments on this thread are from Katty whose trial was literally a next-gen Celebrex taken with Keytruda and she got 7 months on that), so if you do get checkpoint inhibitor consider including some kind of NSAID…
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PS CDK12 levels are reported to help cancers evade the immune system:
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Here is an excellent review of cancer signaling and immunosuppression, it is not breast cancer-specific but it does include all of our heavy-hitters:
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@cure-ious Wow! Thanks for all the info.
The CDK12/13 trial was low on my list, but I'll scoot it up some for sure. You posted a while ago about the introduction of NSAIDS for liver mets, so I started taking 800 mg. a day of ibuprofen. I have a physical with my primary in December, I'll ask her for a Celebrex script. I have arthritis in my neck and hips and I actually could use a better anti-inflammatory.
The articles made my brain cramp, lol, but I will try again later.
Thank you!
CBL
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update on CDK2 inhibitors, for cancers resistant to CDK4,6i.
Currently in clinical trials: INX-315, BLU-222, AZD8431, PF07104091
Ideally, one would want a CDK2 inhibitor and a CDK4,6i because the two are like a toggle switch (if one goes down, the other goes up). And for cancers with ESR1 mutations, an oral SERD rather than Faslodex.
INX-315 with Ribociclib and Faslodex (NCT05735080)
BLU-222 with Ribociclib and Faslodex (NCT05252416/VELA)
AZD8421 with Ribociclib and Camizestrant (NCT06188520/CYCAD-1)
RGT-419B a CDK2/4i with SERD, SERM or AI (NCT05304962)
PF07104091 (Tagtociclib) trial recently finished, Pfizer has published data on combining it with their new (stronger) CDK4-specific inhibitor (Atirmociclib), however I don't see a trial of this combination with Faslodex or an oral SERD thus far.
https://pfizermedical.pfizerpro.com/api/vc/en/medical/assets/923f7b27-3b5e-4a40-b822-6dd717c055cf/Shen_P_5709_AACR2024.pdf
This class of drugs has been beset with toxicities, so hopefully they have it figured out. These trials are for CDK4,6i-resistant or Cyclin E (CCNE1)-amplified cancers.
A new type of CDK2-targeted drug, called a molecular glue degrader, looks to be very effective in pre-clinical work and does not have off-target effects that the above drugs have, so it may have fewer side effects. Here they look at head-to-head comparisons, however this degrader is also not yet in clinical trials The company does have a trial with a molecular glue degrader of cMYC…
https://ir.monterosatx.com/static-files/bf6600fd-9989-44ec-8ea8-063b61b7b829
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This news release has info about the Bria-IMT vaccine results:
- Among 36 patients with post-dose cancer-associated circulating tumor cell (CTC) data, patients with post-dose CTC count < 5 had a significantly better OS compared with a CTC count > 5 (13.4 vs. 5.5 months, P 0.01).
- Patients with positive delayed type hypersensitivity (DTH), an inflammatory marker to measure the response to Bria-IMT™ immunization, had significantly better OS.
I've had three treatments of the vaccine only and mild progression. The recommendation is to continue the trial and add the inhibitor (Zyrlyx) to the treatment. However, I don't have a delayed hypersensitivity, which would suggest the T-cells are working, but an immediate response which indicates the B-cells are working. The response is becoming more immediate with every dose. Fortunately, I'll be speaking with an actual doctor on Tuesday so I can ask him why it benefits me to stay on this trial. I don't see the reasoning.
My Signaterra result before the trial was like a 1.5 or something and I'm having the test again run on Friday. We'll see how far that's jumped up and if it's not under 5, I need to move to a different trial.
At least that is my thinking—we'll see what the doctor says on Tuesday.
CBL
P.S.—Happy Thanksgiving!
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CBL, thanks for the update & new info- what is a Signaterra test? Also, when you start a trial, do the doctors have ideas for what the next trial would be, or they wait for Guardant?
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Signaterra is a circulating tumor cell test by Natera. Similar to tumor markers but more sensitive. The doctors have an idea now because the tests weren’t run that long ago. Not sure I’ll need another liquid biopsy so soon but I’ll ask. Might not be a bad idea. :)
CBL0 -
You make the call as to when you want to leave the trial, right? But it would still take a month to apply for another trial, and you would be off meds for that whole time? I'm not clear how trials work…
In the past my MO has sent off for Guardant as TMs were rising but scans were still not showing progression- it takes awhile to get the results (and then to think about what's next)
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Yes, on both counts. I can leave whenever I want, but would be off meds until I found an open slot somewhere and go through the washout period (up to 28 days). Before this one I was off meds for 35 days. I think that’s about standard to find a spot, do the screening tests, do the washout, etc.
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The abstracts for San Antonio Breast Cancer Symposium (Dec 10-13) are online!
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Update from the Bria-IMT trial:
Spoke to the doctor today and it is as I suspected:
He said it is likely I will have progression again at my next scans on December 27th, but recommends I stay on it with the added drug and give it a chance. It's only another 3 weeks, and they have had better results with the combo therapy. But the odds are I will be jumping to another trial after the beginning of the year.
I have a lot of options, so it just depends on what trial is available at the time without a long wait time. My liver numbers actually went down in yesterday's labs, so I'll be curious to see what the tumor markers say tomorrow. If the numbers go bonkers, then of course I'll jump early (or even to SOC if they're way wonky) but for now we're staying the course.
I would've switched now, but I've already been off treatment for 3 weeks, and I didn't want to wait another 3-4 weeks to get on a different trial without treatment. It's possible this is slowing it down a bit since the growth was mild.
Anyway, that's it for this report!
CBL
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Another update:
My tumor markers (which have always been accurate for me) jumped 100 points. I called the trial nurse and told him I wasn't comfortable staying on this trial after this week. He'll speak to the doctor tomorrow morning and tell him my thoughts, and he's speaking with the Aurora A trial people about open slots this afternoon.
So hopefully I'll be changing trials by the first or second week in January. I'm bummed I didn't get more time out of it, but to be honest, I didn't think it would work from the get-go.
CBL
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Hey CBl, sorry for the up & down of all of this, I was just reading that Aurora A inhibitors synergize with immunotherapy, so perhaps the second drug they gave you will actually help the next one work better…
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