Are you currently (or have you been) in a Clinical Trial?
Comments
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Cureious do you have the trial number for the one that has the combination with Halaven??
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Nicole, I was wondering since you are responding to Halaven alone, if you can't go back on the Halaven combo when its approved, or maybe get some Balixaforte now under compassionate use since the trial is not recruiting anymore?
Trial formally ends in March and will continue tracking patients for a year after that. Very fast for phase 3, given that they just started the trial in 2019, why can't they all be like that?
https://clinicaltrials.gov/ct2/show/NCT03786094
Objective response rate (ORR) data from third-line (3L) patients and progression-free survival (PFS) data in all patients in the Phase III FORTRESS (NCT03786094) is expected in 2Q21 and 4Q21 respectively, as per a September company presentation. The company has projected a potential accelerated approval in 2Q22 or full FDA approval based on the PFS data in 1Q23.
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Curious...I just sent you post to my MO....I am hoping that I will hear something within a week or 2. Thank you for that..
Dee thank you also for all you contribute here.
Bev...you as well..thank you.
I feel very overwhelmed and completely lost when looking at trials and you all really help so much with that...I am very grateful. Thank you!
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Moth - thank you so much for your encouragement and also explanation of what you went through getting on your trial. It sounds like a very similar situation. I'm not sure I'd be classed as a visceral crisis yet - I was asymptomatic at diagnosis and now I have a cold and am coughing but can't tell from what (my breast cancer nurse insists i'm imagining any symptoms now just bc i know it's there, which is annoying...) But with lungs I think it can spread quite a lot before you get symptoms. And my fear is spread to other organs as well while we wait...Certainly it is *very* aggressive if we take the max SUV as a signal, which was very high on the Pet scan. I also have things like EGFR amplification, FGFR1 amplification, TP53 mutation, all of which drive aggressiveness. So I feel like we can't mess around (my onc's intuition as well). Your point about not being able to just drop in and stay with friends during Covid is a very good one - somehow I had forgotten that we're going through a horrendous health crisis!
AlabamaDee - that's very useful to know you manage with the 2 hour drive - in theory I work (I'm a university professor as is my husband) but I'm on sick leave now. How long that will go for and what I'll do then are big, existential questions I can't quite face at the moment (!) Also we are doing all work remotely during Covid which makes things a bit more flexible. In terms of getting another biopsy - something transbronchial may be next. The problem is that the lung team have told my MO that they won't get anything better from another aspiration of a mediastinal node, and my nodules are too dangerously-positioned to approach with needles right now. They were suggesting next option would be a mediastioscopy but I'm not even sure that would help. Maybe I need a second opinion from a thoracic surgeon as well...
On Tuesday I have a second opinion booked with Prof. Nick Turner at the Royal Marsden in London, who is the breast cancer guru in the UK - primarily a researcher who sees a small number of patients so I'm glad to have got in to see him. I'm hoping he can help me make a decision and let me know what he would recommend - I'll report back....
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PHET- great news on your second opinion expert! Hoping for a good plan.
I am sorry about the nurse not taking you seriously. People , even nurses, do not understand what we face and how hard this journey is. You know your body - keep listening to it.
Dee
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Many thanks to BestBird for mentioning the new drug Eganelisib as a shining highlight from SABCS2020!!
Eganelisib (like all drugs with the "ib" suffix) is a protein kinase inhibitor, in this case it selectively inhibits PI3K-gamma kinase. It causes the immune cells (macrophages and myeloid-derived suppressor cells) within the tumor microenvironment to switch from a pro-tumor to an anti-tumor state. This drug is being combined with Abraxane (chemo) and Atezoluzimab (immunotherapy) in the Phase 2 MARIO-3 trial as a new firstline treatment for triple-negative MBC. The drug received fast-track FDA approval this year and the trial is expected to fill up within a few months; 60 patients will be enrolled, half being PDL1-positive and the other half not. Preliminary results from small number of patients show an overall response rate (ie, tumors shrinking) of 100% in PD-L1 positive patients and 50% in PD-L1 negative patients. Not clear yet how durable/long-lasting the responses are.
https://clinicaltrials.gov/ct2/show/NCT03961698
- 100% of evaluable patients (n=13) demonstrated tumor reduction
- 69.2% (9/13) overall response rate (ORR) with best responses of complete response (CR) or partial response (PR)
- 100% (5/5) ORR (CR + PR) with 1 CR and 4 PRs observed in PD-L1 positive patients
- 50% (4/8) ORR (CR + PR) with 4 PRs observed in PD-L1 negative patients
- Translational data are supportive of eganelisib's immune modulation mechanism with treatment associated with decreased M2 macrophages and myeloid derived suppressor cells (MDSCs) and increased T cell reinvigoration as measured in peripheral blood.
- The novel triple combination treatment with eganelisib, atezolizumab (atezo) and nab-paclitaxel (nab-pac) demonstrated safety in line with expectations of the component drugs with no additive or new safety signals. The most common ≥ Grade 3 treatment-emergent adverse events were decreased neutrophil count (21.4 percent), diarrhea (14.3 percent), and rash (14.3 percent). Only one patient (7.1 percent) experienced ≥ Grade 3 ALT/AST increase, and this patient had a Grade 3 elevation.
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Cure...I am little confused... does one need to have the PI3K to benefit or just PDL1?
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Nope, the PI3K-gamma inhibitor is there to flip the signaling that's going on within the tumor protecting immune cells, nothing to do with the cancer It's a different variety of PI3K kinase than the one targeted by Piqray, and it seems the side effects are not so bad
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Thanks Cure...so does that mean we all have that and could benefit from the inhibitor?
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cure...my MO just got back to me reference this :
Nicole, I was wondering since you are responding to Halaven alone, if you can't go back on the Halaven combo when its approved, or maybe get some Balixaforte now under compassionate use since the trial is not recruiting anymore?
Trial formally ends in March and will continue tracking patients for a year after that. Very fast for phase 3, given that they just started the trial in 2019, why can't they all be like that?
https://clinicaltrials.gov/ct2/show/NCT03786094
Objective response rate (ORR) data from third-line (3L) patients and progression-free survival (PFS) data in all patients in the Phase III FORTRESS (NCT03786094) is expected in 2Q21 and 4Q21 respectively, as per a September company presentation. The company has projected a potential accelerated approval in 2Q22 or full FDA approval based on the PFS data in 1Q23.
Here was her reply:
For the trial, without the drug being out and knowing who ti will benefit, I am hesitant to ask for it for compassionate use as we have other options and I can't say there is nothing else that we can do on trial or FDA approved.0 -
Yes, I think this drug should increase immunotherapy response for everybody, but for ER-positive cancers we probably need multiple boosters
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Hi phet,
Thinking of you and wondering how your meeting with thw Prof went?
I hope you are doing ok.
Gentle cyber hug.
Astrid.
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Thank you Astrid for thinking of me!
The meeting with the Professor went ok, though it felt quite rushed. Perhaps I had a lot of questions...he seemed more convinced than my team that this is indeed breast cancer so that is a start. He also was more bullish on me really pushing for a tissue biopsy of my lung tumour to try to get on an immunotherapy trial. He warned me that it is true it just may not be possible (what the lung team at my hospital are currently suggesting) but said it was worth exploring every avenue. When I worried about how long it would all take he said it would not affect my survival to wait some more weeks - not sure how he could be so certain! He just said it would a matter of managing the anxiety of the wait...
I had really hoped he would go into detail with my Foundation One as he is a research professor who specialises in genetic bio markers among other things. But he didn’t indicate he saw any smoking guns in there. The only thing he highlighted is my RB1 mutation, which he said is the subject of early phase trials now and I should look out for. Has anyone heard anything about RB1 mutations as targets and know of any trials? He said this would be down the line as an immunotherapy trial would be preferable first.
I have a lot of mutations show up in the section on ‘variations of unknown significance’ - 23 or so. Some of them seem quite significant really...like a MHS2 variation (a Lynch gene I think?), and two genetic mutations that belong to the same family as BRCA - RAD54L and FANCA. I asked if this meant I might be a candidate for PARP inhibitors without BRCA or if the MSH2 helped with immunotherapy. He was quite against me reading anything into those mutations - because they come under VUS he said we can’t assume they’re doing anything in driving the tumour. But I was a bit confused by that - I though VUS just means that there isn’t enough literature on those mutations and breast cancer, not a designation that the mutations aren’t doing anything. Does anyone have any light to shed on that? The trial I am hoping to join is KEYLYNK and it starts everyone on Keytruda and gem/carbo, then randomises everyone to continue with that treatment or continue with that treatment plus olaparib. You don’t need BRCA for the olaparib I don’t think. So I’d be very interested to know if the FANCA and RAD54L mutations might make that more likely to work.
In terms of my decision moving forward - it all comes down to being able to get this lung biopsy, without which I cannot join the trial anyway. Frustrated with my hospital (to be honest I think the biopsy might be tricky but also this is about COVID - I’m not a priority to get the biopsy In the middle of COVID when there’s a chemo they can just put me on that is SOC) I’ve contacted a thoracic surgeon in London to ask about having it done privately. He comes highly recommended and also works at the hospital where the trial would be so that might help. The trial coordinator emailed me yesterday after I asked about timeframes and said, again bc of COVID, that even if I can get the lung biopsy soon we’re looking at mid- February before I’m on the drugs with all the scans and tests they need to do. That would be 12 weeks since diagnosis, and is a best case scenario time-wise. That scares me somewhat. In the meantime my oncologist has made an appointment for me to start gem/carbo on the 19th Jan. so I have until then basically to make a decision and decide whether to go ahead with it or not.
Such difficult times we’re all in
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PHET
I am sorry you are going through this. Have you talked to the trial intake person? She could shed some light on how that trial works for washout periods. Some trials are 4 weeks, and some are 2. If you start your chemo and schedule your biopsy, maybe you could still get in later.
Hoping you get some clear answers.
Dee
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Thank you Dee
the waiting is the worst, isn't it! I've spoke to the trial intake person and she said it's about 3 weeks to get everything organised. I wouldn't be able to do the trial if I've started chemo though as it's for first line treatment...it makes things high stakes! 0 -
Phet, Is this Nick Turner? He is phenomenal, I'm surprised he even sees patients he is so involved in the research. He is maybe noncommital about the DNA repair mutations because most mutations that affect cancer growth have been identified in these genes, so having a mutation of unknown significance does not suggest any likely effect on the activity or expression level of the protein. Hard to hang your hat on that.
So he is suggesting immunotherapy as a firstline treatment, do you have a link to the trial? He is correct to say the exact timing is way less important than what road you embark down, and that the waiting may be the hardest part. I would still try for immunotherapy, 1) Standard chemo would involve a fairly short PFS, and the cancer may be more aggresive when it progresses; 2) Immunotherapy, if you respond at all, tends to come with a overall survival benefit, even if you progress sooner rather than later- just the improvement in the overall immune function I guess may make subsequent treatments more effective? Not sure why it is; and 3) immunotherapy purportedly works better earlier than later in treaments- best of luck!
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Cure-ious - yes it was Nick Turner
and his research profile is indeed why I wanted to see him! I saw him through private practice (as opposed to the NHS which is what I'm otherwise treated on) - it's possible he reserves a few hours a week for private consultations which is how I managed to see him so quickly. I see what you mean about the DNA repair mutations. I guess I was hoping that long list gave me more options, but I understand a bit more now about the grey area that is variations of unknown significance!This is the trial we're talking about me going on: https://www.clinicaltrials.gov/ct2/show/NCT0419113... Technically it's to test the improvement from Olaparib, but as Keytruda isn't approved for TNBC here like it is in the US, it would primarily be a way to get me guaranteed Keytruda. The Olaparib, if I ended up on that line, would be a potential bonus (though I'm not BRCA1/2).
That's very interesting also about the longer OS on immuno even when there's not always longer PFS - I didn't know that! Another reason to push for this....
The issue is the lung biopsy! I'm on the phone again today ringing around trying to find someone to do it for me privately. Problem is all the thoracic surgeons and chest radiologists are busy with Covid. Totally understandable that they are, but Cancer is important too! I'll report back here how my success goes....
x
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Phet,
It's all good- a LOT more people respond to PARP inhibitors than just those that have mutations in BRCA or other DNA repair proteins- sometimes the DNA repair proteins stuck in ribosomes, and not available. There is no test as yet for the latter scenario, tho they are working on one, so its good if you have access to the drug anyway, its no less likely than any chemo would be to have an effect on your cancer
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Also, for Phet and BevJen and anybody else contemplating immunotherapy-
Statins, which inhibit the Hippo pathway and can have good anti-cancer activity (strongest is the new statin, pitavastatin), they are also reported to benefit immunotherapy response rates
For non-small cell lung cancer:
- Overall response rate improved: 32% vs. 18%
- Median progression-free survival: 6.7 months vs. 2.9 months
- Median overall survival: 13.1 months vs. 8.7 months
- and similar or slightly larger benefits were seen for mesotherliomas
- https://www.asbestos.com/news/2021/01/07/statins-b...
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Cure-ious,
Wow, that's pretty interesting about the statins. However, my internist will not prescribe statins for me -- I asked her before when I was on the Jane McLelland kick -- and I doubt that my MO would do so, so I guess I won't be doing that. Big sigh.
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super interesting about statins. Alas, I have very good lipid panels...I thought letrozole can cause high cholesterol though? Should i be crossing my fingers for that lol. I don't think my MO will rx statins based on those very prelim reports
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My trial won’t let me take my Lipitor because it interferes with the trial drug. I can’t remember how. I specifically asked for Lipitor when my cholesterol went up knowing it has some anti-cancer benefit. I could take Crestor but I didn’t want to start 2 new drugs (trial & statin) so we will check lipids in Feb
today that heavily pretreated patients don’t do as well on immunotherapy, especially if they are low tumor mutational burden, not micro-satellite and not pdl1.
The researchers aren’t giving up in trying immunotherapy for my subtype though.
Dee
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Well that stinks (about patients heavily pre-teated not doing as good)..... I just cant catch a break....
At least I have PDL1 10% my TMB is Intermediate...or was at time of diagnosis it must be higher now though...
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Can I hear from some of you that have become endocrine resistant or ESR1 mutations. Is it only chemo from this point only? Anyone on chemo for a good amount of time. Trying to see if I should just give up or let the chemo kill me first...I'm on Gemzar/Carboplatin. My foundation 1 came back with High mutation burden so Keytruda is a possibility, but my ONC says there are toxicities to that treatment and I have the ESR1 mutations and have tried falsodex only worked for a few months. I'm only 15 months in and on my 3rd line, Xeloda did not work. Also I have the acquired BRAC1 mutations. Trying to get into Duke because I heard they have some trials that are on some new SERDS when you become Endocrine resistant.
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Imagine, if you have somatic BRCA, then shouldn't a parp inhibitor be added? Olaparib (lynparza) is the one I hear about most.
There is a keytruda thread here somewhere - immunotherapy is nowhere near as toxic IMO as chemo. It can have severe autoimmune effects such as crashing your insulin regulation, thyroid, or really bad (& possibly fatal) skin effects but really, my understanding is those are very rare and less likely than neg SEs from chemo. My immunotherapy (tecentriq) has really been pretty easy on me.
As far as chemo - I'm still on a taxane since March. Most of it has been weekly taxol but last round we switched to abraxane. Not sure I'm going to stay on it as I had more severe SEs than on the taxol. But anyway, that's been >9 mos on 1 chemo (+ immunotherapy). I scan at the end of Jan so we'll see how it's working.
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imagine
I hope you get into Duke and they can help you with your options. It sounds like you have several. It’s true that keytruda has the potential for some tough side effects, But I know of one person who achieved NED on keytruda.
Since you have only had CdK 4/6 with Faslodex and 2 chemos in metastatic, you should qualify for some of the new serd/serm trials.
I just read the first/early results on my trial and it got my hopes up with a few partial response and easy tolerated. (The company’s stock doubled after their announcement in December)
FYI- how are you doing on Gem/Carb? My MO wants to keep me to keep trying targeted therapies as long as the tumor growth does not explode. Wish I was a candidate for immunotherpy. I read it can even help later on make future treatments more effective.
Let us know how you do moving forward
Dee
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Imagine- they are doing a SERCA (Selective Estrogen Receptor Co-Valent Antagonists) trial - It is not an AI, SERD or SERM, something new- The company is H3 Biosciences. You Need measurable disease,(not bone only) almost accrued at UCSF- the trial is called H3B6535. They are testing both ESR1 mutated and those without it.
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AlabamaDee
Are you on the ARV-471 trial? I have been reading some really good results on that drug. Sounds very promising. If you are on it do you have to travel
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Imagine, you maybe shouldn’t rule out Keytruda. Yes, there can be serious side effects from it but there are also many stories of great responses. I have been on Keytruda for about 18 months due also to a high tumor mutational burden and I’ve been NEAD since the first PET scan 3 months after starting and I’ve had only mild and manageable side effects. In my nearly 6 years of dealing with MBC, I’ve blown through a number of treatments prior to Keytruda although I’m ER/PR- and HER2+ so they’ve been different than what you’ve been on. Anyway, I think that MOs are getting better at recognizing sooner when Keytruda is causing potentially scary side effects and treating them more quickly than when the drug was new. Just wanted to share my positive exsince you were wondering if maybe you should give up.
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MargaritaMS,
I am starting keytruda on Jan. 19th. You are only the second person on the boards who I've found who has been on keytruda. Would you mind elaborating on your side effects? Or could you PM me? Thanks much. I will also be going on for high tumor mutational burden. Also, have you been on every three weeks since you started? Or did you switch to every 6 weeks once the FDA approved that?
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