Are you currently (or have you been) in a Clinical Trial?
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Dear Susan, it is pretty simple to get DC vaccine here, as there is one company that produces them under state license for "investigative cell therapies", so you go through their doctor multidisciplinary board (can also be your board at NCI), make 1000 blood tests, sign an agreement and they draw your blood - 150-400 ml. Then there's a process how they separate these immature cells from blood, charge them with either your tumor antigens or general cancer cell line antigens, grow them till they mature, and re-infuse them into you. My Sandra got 8 doses trained with HER2+ BC cell lines, that were administered during 2 years, 5 million cells each. We also had CIKs (cytokine induced killers) made along and got 4 doses that were administered, 1 billion cells each. CIKs work as a passive immunity, i.e. they are "angry" cells, go and kill c-cells, live not long in your body, while DCs play part in your active immunity - travel to your LNs and are maternal cells to transfer information onto your newly produced WBCs. DCs live in your LNs for many years (5-10) and do their job but it takes time (6-9 months) until that immunity starts to work. Main question that remains: DCs are additionally trained with antigens might be not that effective when C mutates, and it does mutate:/ I was always told by our doctors that DCs work in cooperation with other therapies and complement them. There's a very nice and simple book about those things. It is in Lithuanian but could easily be translated into English online. The link is this one: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&so... If someone needs a translation which I have in PDF, just PM me with your e-mail address, and I can send it to you.
Your Saulius
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Thanks for the update on ARV-471 Cure-ious. This is one trial that I was hoping to benefit from.
For anyone interested in CDK2 inhibitor BLU-222 phase 1, I started Thursday. It’s been a bit bumpy but I’m still hopeful to make it work. I spoke with my doctor today and if things continue to digress, we can lower the dose. I’m going tomorrow for some IV hydration. Wish me luck because I really want this trial to be the magic I need
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Thanks for the update on ARV-471 Cure-ious. This is one trial that I was hoping to benefit from.
For anyone interested in CDK2 inhibitor BLU-222 phase 1, I started Thursday. It’s been a bit bumpy but I’m still hopeful to make it work. I spoke with my doctor today and if things continue to digress, we can lower the dose. I’m going tomorrow for some IV hydration. Wish me luck because I really want this trial to be the magic I need
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Best of luck rk2020!
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Best of luck rk2020!
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For anyone interested in my Phase 1 CDK2 inhibitor trial experience, read on.
After signing the consent, I was sent for an EKG, chest/abdomen/pelvis CT, CT of brain and a liver biopsy. I was given the green flag to start the new drug on Dec 1. This required arriving at 7 am for an initial blood draw checking for everything under the sun as well as the most complete urinalysis I've ever had. They ran all 3 tumor markers. After early stage, CEA never moved but it's moving nowadays and actually more then CA27.29. If nothing else, it was nice to get such a thorough work up. Then they put me in a recliner with a halter monitor. My first dose was 8 capsules. I'm like a pelican and I've never had a problem swallowing pills but these seemed to glue themselves together in my throat. And cancer drugs have never made me nauseous before but this one sure did! Before I knew it I was barfing. Ugh. Only one capsule shell came up but how much medicine was with it? Was the nausea related to something I ate (I had a tummy ache the night before), nerves or the drug? I was told to expect diarrhea but not nausea. So far no other patients had reported nausea. We soldiered on. I forget how many but I had something like 10-12 small PK blood draws. I was in that recliner all day and was not released to go home until I took my night dose and the last halter monitor reading was recorded. 7 am to 8:45 pm is a long day to sit in a chair. I didn't feel great after my second dose but I didn't throw up. Unfortunately, they do not want me eating 2 hours before or 1 hour after I take a dose. It would be so much easier if my belly wasn't so empty when I take the pills.
On day 2, minor nausea and diarrhea kicked in about the same time I took my night dose. Day 3…I had to take lots of Imodium and Zofran (first time ever) which gave me a screaming, light sensitive headache. All I could get down was half a banana and some rice. Day 4…oh boy…the nausea and diarrhea kicked up a notch and now I had blurred vision. If I tried to concentrate on looking at the clock on my phone, the numbers jumped around which gave me an overall blurred vision effect. I called my doc. She called in Compazine. It was a truly miserable day. I felt poisoned but when I wasn't sleeping, I was able to eat some ramen and a little mac n cheese. Day 5 was a repeat but I did feel better for awhile after getting some IV hydration. Day 6 was more of the same. I slept all day. From the moment I called my doc over the weekend, she or her nurse were in constant contact with me. It was decided to stop taking the meds. Praise the Lord. Even after sleeping most of the day, I slept all night like I haven't slept in years. If nothing else, this dosage was a good sleeping pill. 🤦♀️ I woke up the next morning and it was like a switch was flipped. I felt great and got lots of chores done.
Day 8 - I had my regularly scheduled doctor visit. Nobody except me seemed concerned about my weight but after days of diarrhea, I had gained 4 lbs in 1 week! My ideal weight is between 116 and 120. I weighed in at 124! I had a belly like I was finishing up my first trimester. They reduced my dose by 50%. Instead of 8 pills twice a day, I was now to take 4 pills X 2. Phew. I felt this might be doable after all. And I got more IV hydration. So now I'm doing my best to keep some food in my stomach but am still experiencing waves of nausea all day. I will probably start taking compazine tomorrow but I wanted to give the CDK2 inhibitor a few days without anything else. This way, I can report very accurate side effects. On the bright side, other then some anemia, my blood looked pretty darn good. I thought for sure my ANC/WBC would tank (it sure did on Ibrance) but it's still pretty good. And my ALT/AST are already improving. And no more diarrhea.
Next week I go for a second liver biopsy and my last long day of monitoring. I will see my doctor weekly through the end of January. If I'm given the green light to continue after my Jan 23 scans, then I can move to monthly visits.
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Oh boy rk2020 that is a rough start:( I hope this next week at the lower dose gets waaay better.
I've done a couple of Phase 1 trials with the day long PK tests but I have tolerated them well and the biggest worry I had was what to watch on Netflix. Not barfing. I'm glad that they followed you closely and helped you manage the side effects
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Whoa! rk2020- that sounds incredibly intense! I am so glad that they cut the dose in half- somehow your description reminds me of years ago someone describing her being in a phase 1 study of a CDK 2,4,6 combo- I am so glad that you are tolerating the drug well and that your labs are holding up. I am very interested in the potential of this drug and hope that it is a good one for years.
Do you have CCNE? are you ILC?
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RK2020-Whoa!!! I agree with Nkb, my first thought was the woman taking the CDK2/4/6 combo a couple of years ago, where they had to keep on reducing the dose (or she would have dropped out), and I see that drug is still in trials. With CCNE amplification, the cancer is getting hit hard, hoping these guys can get the dosage down...
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rk2020,
Hoping they can find the right dosage for you. These Phase I trials are brutal. Wish we could still qualify for Phase II trials.
Hope things get better quickly for you!
Hugs, Susan
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Double posting from Liver Mets thread:
Enhertu was unlikely to work for me since I had already been on Trodelvy (which worked great!). They both deliver a similar Top I inhibitor. Patritumab Deruxtecan and Datopotamab Deruxtecan also deliver Top I inhibitors. All four have different antibody targets but it doesn't matter if I am already resistant to the toxic payload. The trial drug, ARX-788, that worked for me was a dual toxic payload so I had a great but short response to that. Unfortunately, they stopped the trial for commercial reasons. I was hopeful it could help many others.
So what seemed like a whole new world of ADCs with limitless combinations turns out to be mainly one chemo. The only one I can see out there that's different is Zilovertamab Vedotin. Targets ROR1 and delivers an MMAE.
I started on the PY-159 trial almost two weeks ago. It's immunotherapy. It's taken with Keytruda which I already know doesn't work for me but my last lung biopsy showed I'm PD-L1 positive there. I believe there is a lot of heterogeneity in my tumors now that they are everywhere (brain, eye, lung, liver, bone, heart, breast, and more). The liver and heart are relatively new. Everything else was there from my original mets diagnosis. The SEs of the trial drug for me are joint pain, fatigue, coughing, red spots on my skin. These are all tolerable with some Tylenol, Ibuprofen, cough syrup with Codeine, and rest.
Hugs, Susan
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Susan, You are my hero!!! No idea how you are so tough and graceful at the same time. This is such a good choice, hope it works!!!
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Susan
I am in awe of your knowledge and tenacity in handling this beast. I wish the best of results for you.
Eleanora
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Thanks, Cure-ious and Eleanora! woke up this morning and saw your messages and it really lifted me up.
Our Mets in the City support group is having a holiday party today and the sky is clear and blue!
Hugs, Susan
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An interesting new target and drug(s) for immunotherapy and metastasis:
A risk with checkpoint inhibitors is that a small subset of patients actually see their cancer progress even faster after taking drugs like Keytruda, a situation called hyperprogression, which necessitates going off the drug and treatment with steroids. New studies indicate the problem here is activation of an inflammatory signaling pathway by the protein NLRP3, and they show that inhibitors of NLRP3 not only prevent this problem, but also intrinsically inhibit metastasis.
Here is an intro to NLRP3 drugs (there are several different ones) that have been in development to fight Covid and other inflammatory diseases:
https://www.the-scientist.com/bio-business/pharma-...
And a new paper showing that NLRP3 can accelerate hyperprogression and metastasis:
https://www.science.org/doi/10.1126/scitranslmed.a...
Here is Dapansutrile (an NLRP3 inhibitor) in clinical trials (for melanoma):
https://medicine.duke.edu/news/duke-oncology-resea...
Here is a company in the process of testing three different NLRP3 drugs in clinical trials (one of which works in brain):
https://www.nodthera.com/news/nodthera-announces-c...
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Thanks Cure-ious. Definitely some risks there.
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Dear Cureious, thanks, very interesting. What I was always wondering, if it would be possible to cause hyper-progression and then kill all these cells with chemotherapy, as just before/during cell division, cells are most vulnerable to some chemotherapies. I know it might sound immature, and hyper-progression is still poorly understood but still... Some radical remissions have been observed after quick progressions too. Maybe in another life I will be a clinical investigator and could research this?:/
Saulius
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Ha, Saulius!!! You have such a flexible brain, you would do great in science!!! I don't think many of us would wish for hyperprogression to see if chemo would work better, but maybe there are enough people who've had it now where they would know if it helps with subsequent chemo. This reminds me of HIV infections, where the rage for a long time was to get a drug to induce the virus to come out of its reservoirs where it was hiding from the immune system and start replicating to get a massive infection going, with the idea that subsequent anti-virals would then be more effective...
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Rather, the hope here would be to take Keytruda with an anti-NLRP3 drug, which would protect against hyper-progression and also provide anti-cancer activity. I guess some cancers would also need a third drug (more likely monoclonal antibody) to better expose the cancer to the immune system.
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Dear Cureious, my Sandra experienced sort of "hyper-progression" when she was diagnosed. I tried to calculate tumor doubling time in volume (her ki67 was >70%), and it was in range 7-21 days... you could literally see tumors and lymph nodes enlarging every day, liver failing. Very scary:/ But then after 3 doses of docetaxel, i.e. after 8 weeks everything was simply... gone... and doctors were scratching their heads. Sure, some cells were left, and she had these two local isolated progressions (that we handled) but then I think we were very lucky that so many cell divisions happened so quickly and chemo killed them very effectively. This is where I came to think that causing non-chemo resistant controlled hyper-progression could do the trick... Your HIV example is amazing - I did not know that one.
I know they always look for less toxicity but that comes with a paradigm that cancer is a long run battle. I think some strong and healthy or young people could go for something more radical and short-term very toxic in order to be cured. Something like this also happened with first blood/lymph cancer patients and CAR-T - a very radical method, and it does not work for some but you have no choice and you choose those 50 % to be cured...
Saulius
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Cure-ious, thank you for the NLRP3 inhibitor trial information. I hope you and other posters don't mind the intrusion: I'm not mbc but have progressive radiation induced pulmonary fibrosis which was halted with prednisone and O2 before it got to my other lung. While I use inhaled corticosteroids for SOB and the cough, it could start up again so I'm on the lookout for possible treatments. Lab research has shown NLRP3 inhibitors stop the out-of-control scarring but there are too few RIPF bc/Hodgkin's people to run clinical trials (they can't get the numbers even in China) and the lung cancer patients are overly comorbid. While my pulmonologist always tells me that mouse lungs are not human lungs my MO would go to bat for me (and pull strings) if the science and human safety were both there.
Maybe someday these anti-NLRP3 drugs can be used in conjunction with all of the treatments which have ILD black box warnings so that anyone who develops pneumonitis can stay on a drug that is stopping the cancer progression.
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Maggie, It sounds like several pharmas are very keen to get these drugs to trial, so hopefully safety data will come sooner than later. You make a great point that this drug could help with other side effects- and pneumonitis is a problem for many of the cancer drugs, including the CDK4,6i...
Here is a review of how the field looked in 2020:https://cen.acs.org/articles/98/i7/Could-an-NLRP3-...
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Saulius, Definitely making lemonade out of the lemons there! For years I was just skeptical of the HIV plan (to get viruses to replicate madly in the reservoirs where they hide from the immune system so that targeted drugs can get at them), sounded so dangerous and the drugs were never going to take out every infected cell, however I later realized I was being too literal, its all a balance- you just need to kill enough so that the immune system can get the rest- same with the cancer, just beat enough of the cells back and try to get it where the immune system can go hunt the residual
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Dear Cureious, exactly, you are right... someone has posted here somewhere a clip about cancer in big animals, for which their organs are too large to be compromised, as cells on the outside of big tumors hinder cells inside to get blood and these cells die, so that these tumors almost never exceed capacity of the organs to function tight, i.e. most whales live with cancer and do not care. Lower tumor burden is very important. If we can keep it low enough forever - it is a cure, i.e., as you said, balance. NED people also are in some sort of balance, and maybe they have cancer cells left, maybe not, no one can tell. So, yes, balance. An HIV "cure" example that you gave is a brilliant one!
Saulius
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Some happy news coming out of SABCS- The SERD Camizestrant (AstraZenica) showed statistically significant improvement in activity over Fulvestrant, which like the other SERDs, is highest in those cancers with an ESR1 mutation. Unlike the others, however, the drug also bested Faslodex even for those without the ESR1 mutation! Also of note, a CBR of 42.3% was reported among 52 patients in a Phase I Camizestrant study, where 82% received prior Faslodex.
https://www.onclive.com/view/camizestrant-provides...A large phase 1 trial has been ongoing since 2018 that tests Camizestrant alone or in combination with palbociclib, everolimus, abemaciclib, or capivasertib:
https://www.clinicaltrials.gov/ct2/show/NCT0361658...
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cure-ious,
Thank you for the posting. Good news indeed especially for those with ESR1 mutation. I got no mileage out of Fulvestrant - none. Do I understand correctly that Camizestrant is still in trials, and does not yet have FDA approval? The long wait for new drugs is frustrating and unfortunately there are no trials for Camizestrant in my area. But another new SERD, Elacestrant, will hopefully get FDA approval soon.
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WeninWI,
Yes, you're right, Elascestrant is rumored to probably get FDA approval as early as Feb, but I could not see where they are as far along with Camizestrant. In lab studies the ESR1 Y537S mutation is not much inhibited by Faslodex, so that might be why it didn't work for you? All the SERDs and Lasofoxifene seem to do a good job on ESR1 mutations, including Y537S, and often the mutation is no longer be detected in a month or two, and the cancer cells return to normal ER activity.
The SERENA-6 phase 3 trial testing secondline Camizestrant plus Ibrance for ERS1 mutant cancers is not expected to stop recruiting till next Sept, so maybe could go to the FDA in 2024?
https://www.clinicaltrials.gov/ct2/show/NCT0496493...
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Interesting new study in Nature Cancer uses mRNA technology to express in cancer cells a protein that enables TNBC cancers to better respond to immunotherapy, early days but a big result in the mice that got the boost...
https://www.fiercebiotech.com/research/mrna-therap...
Here is the article:
https://www.nature.com/articles/s43018-022-00339-4
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Hope Rugo (UCSF) summarizes the trial for the AKT inhibitor, Capivasertib, together with Fulvestrant on patients progressing on firstline AI+CDK4,6 inhibitors.
Bottom line is good response, better in those with PI3K/AKT/mTOR mutations but decent response even in those cancers without the mutations, and does not have much of the problems controlling blood sugar that are seen w/Piqray. Most prevalent SEs are diarrhea and rash, manageable with drugs...She indicates FDA approval could come this year:
https://www.onclive.com/view/capivasertib-fulvestr...
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Nothing but bsd news today. I just got out of the hospital today. Turns out PY-159 + Keytruda did nothing. I had some massive progressions as well as pericardial and pleural effucions. I also have blood clots in my lung. I'm on oxygen and can barely make it to the bathroom. Can't eat or drink much because my tumors are pressing on my stomach.. No reasonable treatments left. I'm dying. Considering whether to invoke my End of Life Option that I signed last year. Will talk to my palliative care doctor about options tomorrow. Anyone else look into this option? A friend of mine with MBC did it a couple of years ago when she was only 32.
Hugs, Susan
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