Are you currently (or have you been) in a Clinical Trial?
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Thanks for keeping us posted, CBL. You are one strong person.
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Of course! Knowledge is power. I'm not sure how strong I feel since I just faceplanted getting out of an Uber, haha, but thanks for the compliment. We're all pretty damn tough I think to be going through this!
CBL
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So, a rare but deadly consequence of MBC is the spreading of mets to the membranes outside the brain and spinal cord, which is nearly impossible to treat. Joan Massague's lab at MSK discovered these mets are highly dependent on scavenging iron, and can be inhibited by iron chelators (compounds that stick to and bind up the free iron). A clinician at MSK is doing a phase one clinical trial and seeing some very encouraging responses- here is one patient's story:
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@cure-ious Thank you for that. I suspect LM may be in my future, this is very informative and encouraging.
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@cure-ious Thank you for this very interesting information. I read an article explaining the implications
of iron and chelation therapy. I didn't really understand this topic and it's now much clearer thanks to you... let's hope that research moves forward quickly to help people with LM.1 -
Hi everyone, it's been a while since I've posted but I check in often to see how everyone is doing and the news on this thread. I completely agree CBL knowledge is power and I am grateful for all of the experience in trials and treatments you bring to this thread. @cure-ious thank you for all of the clinical news and updates. I've been on Xeloda since the end of last September. I really love that drug but it doesn't love me anymore. I am really sad to move on. I don't know if you remember but I was in a very bad way Christmas of 2023 and in the hospital on oxygen after afinitor gave me a bad case of pneumonitis. I was off treatment and had major progression. Truqap helped settle things down but was short lived and then Xeloda cleared all of my liver mets and all of my bones mets and pelvis mets but one single met in my T9. So we used proton radiation to try and achieve NEAD but the Xeloda has stopped working. My scans showed numerous liver lesions up to about 25% of my liver, and many bones in my spine, pelvis, and hips. So my cancer got aggressive and angry. My primary onc saw me yesterday and suggested Trodelvy and looking into a trial possibly. I wanted to try the new triplet combo with ibrance and itovebi but she thought it was risky. On my last Caris report a year ago when I started Xeloda I still had the pik3 mutation but she said we didn't have time to biopsy and wait and see if it's still there and that Trodelvy covered all the bases even if my cancer mutated. She was also leaving the country to India that afternoon because her father is ill so we didn't have a lot of time to talk. I have a second opinion oncologist at UCLA and she sent me 3 trial options that we will discuss tomorrow. I am limited with trials now due to my grade 3 pneumonitis history although it's since resolved and my lungs are doing very well. One trial she mentioned is Bria Cell IMT. There are two other trials that seem very interesting. One is RYZ101-2011 (aka TRACY-1) trial. The other is Radionetic R10602. They are radioligand trials -- basically you get a special PET/CT to find out if your cancer has a specific protein on the surface. If it does, you can receive an infusion of a medication with a little bit of radioactive material attached to bind to that protein. It seems to be very new in Breast cancer trials but when I tried to search a little it looks like they've done it in prostate cancer. So I am very curious about it and hoping it might be something promising. Just wondering if anyone has heard anything about radioligand treatment and/or experience with Bria cell IMT?
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MommaCJ, How great to hear from you again, and I'm so sorry that you are in that scary progression place, where the tumors that had faded jump back up again! For the BRIA-IMT trial, you will see some discussion above, its been doing quite well, however these others are new to me, so I'm interested to go read up on them. Also might be good to check w/ the UCLA team if they think you have the time to get new liver biopsy, so as not to miss something potentially action-able, or if you should jump into the next treatment to beat things back before doing the biopsy. Please post again soon as you get more information, I have heard doctors chatting about new cellular therapies that are looking good, but I'm not sure which ones and am digging on that too.
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So here is a poster from the San Antonio meeting last Dec, describing the TRACY-1 trial, which although it is phase 1/2 and was just started a year ago, is being offered at some really top centers.
Some of the points: (1) This is a first-in-class (ie first of its type) of radiopharmaceutical that is targeted specifically to somatostatin receptors (about 1/3 of breast cancers have strong somatostatin receptor expression). (2) It was used in an emergency situation, and resulted in a near complete shrinking of the tumors in a patient with strong somatostain receptor expression. (3) It is being tested with and without Keytruda.
They say their target population are folks who already had 2-4 chemo or ADCs and for sure at least one ADC (eg, Enhertu or Trodelvy), so maybe this would be something to try after Trodelvy? But maybe the UCLA docs think this should be sequenced first, or might be less problematic with respect to pneumonitis, etc?
They have big plans for this trial, which at this very early stage is a good sign of enthusiasm:
■ TRACY-1 will recruit patients in Belgium, Canada, France, Spain, The Netherlands, The UK, and the following
US states: Arizona, Colorado, Florida, Georgia, Massachusetts, Michigan, Minnesota, Missouri, New York, Ohio,
Pennsylvania, Texas, Utah, Virginia, and Washington2 -
In PubMed, there is a more detailed description of the one patient who responded so well to this somatostatin-directed therapy:
One participant was treated with SSTR2-targeted 225Ac-Dotatate as an emergency investigational new drug. This participant, a 59-year-old woman with ER-positive lobular breast cancer and extensive bone, nodal, peritoneal, and pleural metastases, at baseline. The participant had severe dyspnea that required weekly 1–2-L thoracenteses over multiple months. Prior treatment with 11 lines of therapy, including fulvestrant with palbociclib, everolimus with palbociclib, capecitabine, taxol, doxorubicin, alpelisib with fulvestrant, eribulin, gemcitabine, and carboplatin, had failed. The participant’s disease demonstrated strongly positive SSTR2 expression (Krenning 4 uptake at Dotatate PET/CT). After two treatment cycles, there was a complete metabolic response according to PET Response Criteria in Solid Tumors at FDG PET/CT and a partial response according to Response Criteria in Solid Tumors, with only subcentimeter pleural lesions remaining at CT. There was also complete resolution of Dotatate avidity. Pleural effusions, the need for thoracenteses, and dyspnea all resolved within the first treatment cycle. The participant’s cancer antigen 27–29 levels dropped from 1907 U/mL before 225Ac-Dotatate treatment to 292 U/mL after two cycles.
The paper mentions at the third cycle there was small-volume peritoneal fluid, and that turned out to be some cancer but it did not express the somatostatin receptor, so that was deemed progression because of some tumor heterogeneity, cancer cells without somatostatin receptors were able to grow and presumably she is now being treated for that. But the treatment clearly worked well on the cancer cells with somatostatin receptors. Also, because there is well-documented synergy between radiation and immunotherapy, the line of the trial with Keytruda added might allow for good clearing of the somatostatin receptor expressing cells even when the expression is not super-strong and give a good abscopal effect.
This patient didn't have liver mets, so it is an open question for now how well this treatment works in the liver….
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Hi @mommacj,
I thought I'd chime in about Bria-IMT. Somewhere around page 145 I posted about it.
I was on the trial in October 2024. I was in the vaccine only arm but progressed after the first round, so they switched me to the arm with the checkpoint inhibitor. I progressed again, so I went off the trial. The doctor said since my TMB was 5 and my PDL1 negative I would probably progress again, so those are two important factors. The higher the TMB the better and PDL1 positive makes a difference too. I'm not sure why they bothered to put me on it if that was the case to begin with, but I suspect they care more about their trials than the subjects. At least at that facility.
But the good news is I think it slowed it down some and also helped raise my TMB. It's now almost 15 which I believe opens up immunology options for me.
The other options you have sound interesting if your TMB/PDL1 aren't suited for IMT.
Good luck deciding and wish you the best!
CBL
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Thank you so much cure-ious and CBL. That is very helpful information. That is great news about the response the woman had to the radioligand treatment. Thanks for information on Bria IMT CBL. I’m glad it at least opened up more potential options for you. My TMB was 5 last year so that’s good to know. I’m going to ask about a liver biopsy again. I’m meeting with UCLA in a few hours so I’ll post again when I have more information. Thanks so much!
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I had a good appointment with UCLA. She had 4 options for trials she believed would be good to try. 1) BREAKER-101 with PI3Ka:RAS breaker BBO-10203: This is the one she said she would go with first or the radioligand which she found very interesting. 2)TRACY-1 with an SSTR-targeting radioligand peptide- . 3) BriaCell vaccine trial -- but currently on hold because they don't have the pharmacy bandwidth. It is available in the area at other locations. She said this could be a good option but not the best option, the first two would be her top choices. 4) Marengo START-002 with a T-cell agonist + Trodelvy.
I like the idea of the BREAKER 101 because I did have a good response to truqap although it was short lived. She was not concerned that I don't have PIK3ca mutation anymore. She said she doesn't usually ever see it change. My primary onc was concerned about that however. I will be having a liver biopsy soon but it will take a few weeks to get a new report on my current mutations. I also really like the idea of the radioligand trial. It's very innovative and the QOL on it and response could be very good. They are also opening a lot of the radioligand trials at big centers around the country she said so there is some excitement there. However, when I was reading about radioligand therapy I stumbled on an article where Johnson and Johnson had a radioligand dose escalation trial start in 2023 for metastatic prostate cancer and they had good responses and also 4 deaths. That didn't sit well especially with the ILD TEAEs. UCLA is just prescreening their first patient so it makes me a little nervous but at the same time it could be a very promising treatment advance. The other two are options and she said they could work but most likely would have a better response with triple neg patients.
I have never lasted on a drug at full dose so dose escalation makes me extremely nervous but I also want to keep more options on the table so I am going to be praying about which one to prescreen for. I wonder if I can prescreen for both and decide at that point? I'll have to ask. If anyone has any other information on these trials let me know. :)
Cure-ious I was reading back through the thread, how is your trial going? Are you still on it? Hope all is well.
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Thank you for the information on Bria CBL. My UCLA onc said the same thing. My TMB was 5 also and she thought I could try it but there were better options. You have been a pioneer on these trials and I appreciate your insight.
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Thank you to everyone who posts on this thread, I read along often and have a running list of potential options. I've learned so much from your willingness to share your experiences with clinical trials. Love and support to us all!
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MommaCJ, Thanks for all that information!!! We're always very interested in whatever UCLA finds interesting!
I will look up the first trial and come back, but wanted to weigh in on what CBL was saying, keep the BRIA-IMT trial on your list for future because wow if you can get the tumor mutation burden to jump up 10 points that alone would be worthwhile because the recent trial Sara Tolaney did for MBC showed TMB over 14 they saw a 60% response rate for immunotherapy, and those were with ER-positive MBC, the "coldest of the cold cancers"… Anything that can give us a potential new line of therapy, esp something that the cancer hasn't seen before, is obviously a great help! I wish somebody would study this and see if this is something that BRIA-IMT does particularly, or its just random that it happens? On my Guardant and Foundation One reports the TMB went up incrementally from 1 to 10 and now one report says 39, so it can just go up over time in response to treatment I suppose? During this time the cancer also developed ESR1 and PIK3CA mutations, and the latter at least is associated with higher tumor mutation burden. There is very little information about how TMB develops or changes, but its good to know to keep an eye on that.
The other point you raise is also really interesting. These PIK3CA treatments usually lead to a big drop in PIK3CA-mutant cells in the Guardant test, and I've seen where the fraction of ESR1 mutations may also go down, but don't know why that would be. Its a similar situation in Her2-low cancers, where treatment with Enhertu reduces the Her2 levels significantly in like a third of patients. Of course the mutant cells are still around but in much lower numbers. So I've wondered if that means one would be less likely to respond to PIK3CA or Her2 therapy in the future, and maybe its not something that can be predicted because one can get a good response even if the level is not high. But obviously it would be helpful to have any data addressing that question, and doctors would have had some experience with that by now.
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MommaCJ, I just passed six months scans on the trial with the PIK3CA inhibitor, very happy because it does not come with any side effects!
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Glad my rambling posts are helpful! MommaCJ, sounds like you are in good hands and have a lot of information to make your decision. I don't know if you can screen for both, but that would be great. Best of luck with it and keep us posted!
Cure-ious, very happy your trial is working! Yay! 39 TMB is amazing! And the 60% response rate for over 15 is great news. I'm not sure when he'll run another biopsy, but that will definitely be something to discuss.
I have labs/chemo on Friday so I'm hoping for another drop in liver numbers. I haven't had much if any pain since round 2, so I'm hopeful. I saw a post in my Facebook group about a woman on I think it was Enhertu whose liver numbers went down but her scans showed progression. Her doctor was switching her treatment immediately, so I'm glad my doctor is being conservative and not rushing to push me to something else. Talzenna is my next line and it's already been approved by insurance, so I'll be able to start in days once we run scans at the end of September.
That's all for this report!
Wishing health and peace to everyone,
CBL
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Cure-ious, thanks for sharing and simplifying the recent research.
It’s encouraging to know that the new research on radiopharmaceuticals may open new avenues for breast cancer treatments.
Thanks to both Mommacj and CBL for sharing helpful trial information.
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CBL, the person who has run a couple trials on high TMB mBC is Sara Tolaney, and here is a link to her latest paper- as I recall the first one used Keytruda and the second one Nivo-Ipi, which is associated with longer more durable responses to immunotherapy. Here they found 5 people with TMB over 14, two were between 14-20 and three were over 20. Of these, three responded to Nivo-Ipi, and of those 3 two showed long responses of 36 and 45 months. So not a large number of people but very promising responses. Also in the earlier paper they saw that you needed over 10, like 14 to show consistent responses. And she says that those with TMB=10 are not so rare, and if the TMB numbers go up after years of treatments, that high TMB state may become more common. They report that ESR1 mutations (or presumably very high estrogen signaling cancers) may not respond to immunotherapy, and this has been seen also by others, so in those cases one would want to also include an anti-estrogen/Orserdu SERD. For me, if/when I got immunotherapy, I'd also like to try to get PCSK9 inhibitor (a cholesterol injectable drug that synergizes with immunotherapy; but hard to get insurance to cover; it increases exposure of the tumor to immunotherapy and also protects the heart from damage by the treatment, a rare but bad side effect) and prozac-type SSRIi (which activate T cells). So keep an eye out for any future Sara Tolaney trials
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Ooh, excellent information! Thanks so much @cure-ious . I'll take 36-45 months! I have the article saved. :)
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@mommacj Hello. In your first post of August 16th you mentioned two options (studies?) that may work with triple-neg patients. Could you please clarify which ones you are referring to? However, it doesn't sound as though this is something imminent. I am curious, being in the TNBC mets camp and we sure don't have a lot of options.
Thanks!
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Hi everyone,
Update from Friday's appointment…
Well, when last we left the soap opera, As the Cancer Turns, the doctor thought I might have pseudo-progression because my liver numbers went down even though the scan showed progression. However, yesterday when I was due for round 4, my liver numbers had skyrocketed, like by 300-600 points. Yipes! So he ordered a stat CT to see if I had progressed again, and if so, we'd start Talzenna asap. He put a hold on the Datroway infusion.
My blood pressure was 86/60 so they gave me fluids and then did the scan. I received the results last night and yes, I did progress. Not by much since the scans were only 3 weeks apart, but still progression. So I anticipate a phone call on Monday and probably start Talzenna on Tuesday. I don't know much about Talzenna, but I'll do a little research today.
I'm super bummed that the Datroway didn't work, especially since there was evidence to show BRCA mutations did well with it (like 80% response). It wasn't the easiest drug—the fatigue/stamina issues were pretty bad—but I would've gladly put up with it had it worked.
I don't mind saying things are getting a little scary. The cancer hasn't stopped growing in a year and nothing we've tried (two trials, Orserdu, and Datroway) has even come close to stopping it. I sure the hell hope Talzenna works. I think my next option would be Orserdu plus Verzenio, but maybe he has something else up his sleeve.
Anyway, that's it for this report.
Health and happiness to all,
CBL
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You are amazing. I am continually impressed by your strength and intelligent, informed decisions regarding treatment. You are your own best advocate and you're doing an incredible job. You're setting a great example for the rest of us moving through the stages of this process.
So sorry the various treatments have failed you and fingers crossed that the right one is discovered soon. Noticed your comment about Orserdu and Verzenio. I thought Orserdu was only approved as a stand-alone, not with anything else. I will be very glad to hear if that has changed, as I believe that is in my future as well.
Virtual hugs and healing thoughts sent your way.
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CBL, As the Cancer Turns, Indeed (you are so funny)! I'm also sorry you have been though so much lately, not fair!!! Talzenna is Talazoparib, which I recall is the strongest of the PARP inhibitors that is FDA approved and there are stronger ones in trials too, including one that goes to the brain. In addition, they have been seeing good responses combining PARPi with immunotherapy, and you might be an ideal candidate for that combination, no?
In the JAVELIN trial (2021) they found HR+/BRCA-mutant cancer responders got, 15.7 months duration of response. And you have a high TMB…
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Hi @eleanora and @cure-ious
Thank you for all the kind words. It's been a sh*tshow lately for sure, but I'm lucky to have an open-minded doctor so I can bring other combinations to him and won't be thrown out of the office like I would've been with my old oncologist.
He said Orserdu and Verzenio was one combo he could get approved, so I guess some insurance (I have Medicare) companies are allowing it.
I will ask about the JAVELIN trial when I see him and bring him some data, but I have a feeling he's holding on to immunotherapy as a Hail Mary. We shall see.
Thanks again ladies for the support and information. I'm on it!
CBL
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CBL, The Javelin trial is wrapping up (ie, Active but no longer Recruiting), so perhaps he will know if a phase 3 trial is coming, or would recommend considering immunotherapy at a later date and/or with other drug combos. I've only met one MO who was enthusiastic for ER+ MBC with high TMB to try immunotherapy (but that was because she has an exceptional-responder patient who has remained stable for 6 years (including the 2 year treatment). But even after PARPi there are now trials testing adding various PARPi combinations that can re-sensitize the cancer, so it may be a long while before you want to consider it (and possibly TMB may continue go up?). It'll be interesting to hear what Talazoparib is like, Good Luck!!!
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Thanks, cure-ious.
I'm not all that excited about trying immunotherapy at this point because I feel like that would be a last ditch effort. However, if there are combos that might work that's a spot of good news.
CBL
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Hi guys, rolling off of the Pfizer Kat6 trial. It was a good 18 months! Fairly easy SEs. Bones are still stable but one of my liver mets grew too much and they won't allow sbrt or histotripsy so on the Orserdeu.
Thank you for all the research and sharing on this site!!
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perky: Did you have it with fulvestrant? What were the side effects? I’m hoping that trial will come to the cancer center I’m at. I’m trying to stay off elacestrant so I’d be eligible for the oral SERD arm.
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PS Where will your histotripsy be performed tomorrow? Best of luck!
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