Another BiTE gets spit out

[Tall_Allen]

As we are all painfully aware, prostate cancer is immunologically "cold." This means the immune system cannot be coaxed into attacking it. The one exception is Provenge.

BiTEs (Bispecific T-cell Engagers) are in clinical trials. BiTEs are medicines that have one "hook" that connects to a cancer cell antigen (like PSMA) and another hook that brings a T-cell in to kill the cancer cell.

Regeneron cancelled a clinical trial for REGN5678 after 2 men died from immune-related deaths. Last year, Harpoon canceled its trial after early results were toxic and failed to demonstrate efficacy.

fiercebiotech.com/biotech/r...

fiercebiotech.com/biotech/h...

There are still several more in trials.

[garyjp9]

Thank you, TA. Do you know why Provenge seems to be the exception? What distinguishes it from all the other less effective drugs in this category?

[Tall_Allen in reply to garyjp9]

Provenge activates dendritic cells - a slightly different strategy. In India, APCEDEN, which also activates dendritic cells, has been found to be beneficial.

[garyjp9 in reply to Tall_Allen]

Thank you

[garyjp9 in reply to Tall_Allen]

I don't know if a lot of research has already been done on dendritic cell activation, but given the positives of Provenge and Apceden, I hope some are continuing to study it.

[binati in reply to Tall_Allen]

At what stage should one try dendritic cell therapy as advocated by APCEDEN. I am in India so it is an option for me. However, I am currently hormone resistant and had a BCR post radiation after about 2 years. There was no focii found for the PSA increase despite two PSMA Pet CT Scan - one at 0.5 and other at 1.35. Hence, I was put on Nubeqa 7 months ago. Currently the PSA is around 0.04. Post Nubeqa I have options of chemo and Pluvicto etc. only. When should one try APCEDEN's therapy and what are the main risks?

[NickJoy in reply to binati]

Good question- I would also like to know this.

[Tall_Allen in reply to binati]

I don’t know what the requirements are in India.

[binati in reply to Tall_Allen]

I know we generally follow the SOC in this US/Europe in relation to most medical decision making. What I wanted to know is that is it an option for me? Should I do it while I am still in a good situation with Nubeqa? What is the criteria in the US?

[Tall_Allen in reply to binati]

It’s not available in the US

[binati in reply to Tall_Allen]

Isn't Provenge also a dendritic cell immunotherapy?

[Tall_Allen in reply to binati]

It isn't incubated with tumor tissue.

[Seasid in reply to binati]

Did you get the mpMRI of your prostate?

[binati in reply to Seasid]

No

[Seasid in reply to binati]

Did you discuss the FDG pet scan before starting Nubeqa in order to find a cancer?

I have now a similar situation and they are recommending the FDG pet scan to see if the cancer is PSMA negative.

[binati in reply to Seasid]

The MO had suggested, a PSMA Pet CT followed by an FDG Pet CT to see if any cancer is visualized on the scans. This was about 10 months ago. Now when I asked him if he wants to check with an FDG Pet CT he said no there is no need unless you are symptomatic. Not sure I understand his approach. As things stand now I will only know when I have symptoms which will happen when Nubeqa stops working. I will also probably be metastatic by then!!

[Seasid in reply to binati]

What was your PSA at the point of time when you started Nubeqa?

1. Maybe you had micromets?

2. Maybe you had PSMA negative cancer? (This sounds unlikely.)

3. Maybe you had PSMA positive cancer but still wasn't visible on low PSA levels.

[binati in reply to Seasid]

I had a Biochemical Recurrence. I had two PSMA Pet CT Scans - one at PSA of 0.5 and the next at 1.3. These were about 6 months apart. No lesions were found on these so it is assumed that it is micromets. Since taking Nubeqa my PSA has been from 0.8 to 0.4 checked every 3 months.

[Seasid in reply to binati]

Totally above you said that your PSA is 0.04 and now that your PSA is between 0.8 and 0.4.

[binati in reply to Seasid]

My PSA when I started Nubeqa in Jan 23 was 1.47. After a month it went down to 0.04. Thereafter it has fluctuated between 0.04 and 0.08. I was on ADT from Jun19 to Feb 22. I had RT in Nov and Dec 19. PSA started rising in Mar22.

[Seasid in reply to binati]

Why didn't you do the FDG pet scan if it was recommended to you?

[binati in reply to Seasid]

It was discussed but never prescribed.

[Seasid in reply to binati]

Why not? FDG pet scan would make sense if the PSMA pet scan didn't find anything?

[Seasid in reply to Seasid]

I am now in a same position like you. My PSA is rising rapidly but we don't know the origin of the PSA or at least we are not sure enough to radiate the spot (my prostate had a SUV max value of 6.5). What was your SUVMax value of your prostate on the PSMA pet scan?

[Seasid in reply to Seasid]

I don't want to start Nubeqa if it is possible to radiate the prostate and kill the CRPC in my prostate. It looks like that I don't have Mets. My RO refused to radiate the prostate as he believes that the pelvic lymph nodes should be radiated. It is a very interesting situation.

He calls my prostate cancer low grade although it is castrate resistant cancer.

[Seasid in reply to binati]

What was your SUV max value of your prostate? Mine prostate SUV max value is 6.5 at PSA 1.1. my latest PSA was 1.7 and it is rising rapidly. Why didn't you had the FDG pet scan just in case is you have a PSMA negative cancer?

[binati in reply to Seasid]

After radiation my PSA was rising fast - 3 months PSADT. PSMA Pet CT showed no lesions despite rising PSA. Hence it was classified as BCR and no need for FDG scan. In my case I've already undergone RT.

[Seasid in reply to binati]

what does it mean?: "I've already undergone RT."?

Did they radiate you again? I am asking again, what was your SUVMax value of your prostate cancer on the PSMA pet CT scan?

I am sorry if I am reapiting myself. If you don't want to say just keep it for yourself.

[Seasid in reply to Seasid]

I am in a similar situation like you. After radiation my PSA dropped from 1.4 to a minimum of 0.23 in about 6 months following the prostate irradiation. After that a PSA started to rise and my MO ordered a new PSMA pet CT scan around a year after my initial radiation. My prostate SUV max value was 6.5 and my PSA was 1.1. now my last PSA is 1.7 and my RO refused to radiate again my prostate and ordered an FDG pet scan. I don't have any visible Mets on the PSMA pet CT scan and on the nuclear medicine bone scan. My PSA is rising rapidly. My RO think that my pelvic lymph nodes have a cancer but it is not visible on the scans.

I have to now decide to start Nubeqa like you or just do the FDG pet scan and see where is the cancer. I don't feel comfortable starting Nubeqa and my RO doesn't want to irradiate my prostate again despite the fact that the prostate MRI showed a correlation with the PSMA pet CT scan and my PIRADS score is 5.

I am considering finding a new RO. It would make sense to irradiate my prostate cancer again.

[Seasid in reply to Seasid]

Just before my prostate irradiation the PSMA pet CT scan SUV max value was 14 at PSA of 1.25. A year later PSMA SUV max value was 6.5 at PSA 1.1. I did the prostate MRI at around PSA 1.5 and the PIRADS score was 5 and the cancer location was correlating to the PSMA pet scan finding.

[Seasid in reply to Seasid]

My PSA is rising rapidly and I have a CRPC in my prostate.

[binati in reply to Seasid]

My primary treatment was RT and ADT (3 years). I will have to check the reports as I don't remember the SUVMax. Frankly I let the experts do the work of reading the scans. I had radiation of prostrate, prostrate bed and pelvic lymph nodes. I'll check the report and see what it says about SUVMax. You can't radiate the same area again. Maybe your pelvic nodes were not radiated. What was you Gleason grade when you were diagnosed?

[Seasid in reply to binati]

Gleason score was 4+3 and I am on Firmagon injections only and I had early chemotherapy 6 cycles. My PSA nadir was 0.12 and my PSA before starting ADT was 100.

My PSA started to rise to 1.4 and than I irradiated my CRPC in my prostate after the PSMA pet CT scan. The PSMA SUV max value was 14 just before radiation. I received 38 Gy SBRT to my prostate and bought seminal vesicles. My PSA dropped in 6 months to 0.23 but started to rise. Before radiation I didn't have any Mets finding on FDG, PSMA, bone scan or CT. Even now I only have visible cancer in my prostate and nowhere else. I have to do the FDG pet scan. My RO thinks that my cancer in my prostate is low grade SUV max value of 6.5. and he believes that the rapid rise of the PSA is a result of the cancer in my pelvic lymph nodes. I don't want to irradiate my pelvic lymph nodes only on the PSMA pet scan visible cancer and that is in my prostate. The problem now is that my PSA is rising rapidly. The PSA is still low and I am not desperate to do anything until the PSA gets to 2.1 and it will be very soon. I will do than the FDG pet scan and maybe a new PSMA pet CT scan and a new MRI of the prostate and will decide what to do.

As you said after the failure of Nubeqa we will get close to the end of our prostate cancer journey.

I don't want to use the big guns like Nubeqa until I don't have any visible Mets on any scan.

[binati in reply to Seasid]

This is a grey area. Micromets in the blood and small mets in the lymph nodes are not visible on PSMA scans. If you wait to see them in the scans it might be too late as larger lesions only are visible. You should consider seriously getting the pelvic nodes irradiated.

My SUVMax of the prostrate in the last scan was 4.8.

[Seasid in reply to binati]

Good point. I just feel uncomfortable radiating my lymph nodes. I understand the point you and my RO are making. Maybe I could ask my MO what he thinks, but he is really not an expert on radiation oncology.

I started rosuvastatin 40mg, Metformin 1500mg, doxycycline 100mg per day and aspirin. I hope it will slow down the PSA rise.

I may ask for a second opinion from an RO.

You are right I should not wait too long, maybe chemotherapy now and then Nubeqa? But I am not sure if the Australian PBS would allow Nubeqa after chemotherapy. I would need to wait again until my PSA goes up again and that could be too late. It is very frustrating that we have do many limitations in our treatment.

My RO said that there is a small clinical trial which confirmed that after radiation of the prostate the cancer wasn't found in the prostate (they surgically removed the prostate and analysed it.) Even if the prostate had some residual PSMA avidity like me now, but they found a cancer in a surgically removed lymph nodes. I asked him to send that study to me but he didn't send me anything yet. If you know about that small clinical trial could you please provide us with the link to the results and to the clinical trial? I would be very grateful for that.

[binati in reply to Seasid]

Will have to search. You can PM Tall Allen who usually is very aware of all the studies. Get a good RO as he beat advise you. My Gleason Index was 5/5 and PSA was 250.

Reducing PSA by taking Metformin, Doxycycline or Aspirin doesn't help unless you can see any cancerous lesions shrink. You are treating the PSA and not the PCa!

[Seasid in reply to binati]

Maybe yes.

I also want to avoid infection from the cancer. My cancer is PSMA avid in my prostate but the RO thinks that the PSA is not coming from there.

I will ask from my MO for RO recommendation next week.

I don't feel comfortable to get an FDG pet scan now. I did it a year ago and it was ok.

What I don't understand is why my RO said that I just recently had the radiation? It was more than a year ago. I didn't ask him anything as I didn't have a feeling that he wants to talk to me much. Anyhow that is what happened.

[binati in reply to Seasid]

There is nothing to radiate in the prostrate or in the lymph nodes unless the lesion is visible. If you have not had your lymph nodes irradiated there is a case for doing that. You need to check with your RO. Get a second opinion from another RO as well. Does not hurt to have a second opinion. Your cancer will not cause any infection so you don't need doxycycline etc.

[Seasid in reply to binati]

Last time after the FDG pet scan I almost ended up with the biopsy.

I have sleep apnoea.

There is a visible cancer in my prostate but it looks like that not all the PSA is coming from there. I am fine with doxycycline and Metformin. I am taking Crestor to avoid cardiovascular problems I don't take Aspirin every day. Maybe only ones a week 300 mg.

I feel fine and I don't want to jump to Nubeqa as it can cause neuroendocrine differentiation of the prostate cancer.

I don't want to irradiate my pelvic lymph nodes until I see something.

I am polymetastic and I am not curable therefore I don't want unnecessary radiation which could mess up with my bone marrow and immune system.

I undertook prostate radiation in order to avoid local spread of the cancer from my prostate. The PSMA SUV max value of my prostate was 14 and I decided to irradiate it. I had no other findings on any scan.

I am fully aware that this will not extend my life but I wanted to avoid problem with urination.

If my PSA goes above 2.1 I could get another PSMA pet scan to see what is happening.

I agree with you that what I am taking is probably useless and even dangerous. I don't recommend to others but I am doing it.

[Seasid in reply to Seasid]

Interesting read about PSMA avidity in tumors:

prostatecancer.news/2019/12...

[binati in reply to Seasid]

Whatever suits you. You have to decide eventually how you want the treatment to proceed.

[Seasid in reply to binati]

I would prefer if my PSA simply stop rising without any further intervention like introduction of darolutamide. PSA is not a cancer and if you can't see the tumour that is great. I believe micromets will not kill me immediately and I believe it is not easy to them to grow, at least I hope so. I will do the FDG pet scan but will wait until next week to see my MO.

If you find out more about how to get that immunotherapy from India and how much it cost I may be interested as for Provenge I don't have enough money.

[Seasid in reply to Seasid]

Once I will see the lymph node on the PSMA pet scan I will radiate it.

[binati in reply to Seasid]

Look my understanding based on discussion with 2 MOs reputed from different hospitals is that if your PSADT is less than 6 months then you should seriously consider further treatment. If there are only micromets then you have no option but to go for Nubeqa or Enzalutamide. Any delay can certainly result in metastasis sooner rather than later. Even mets won't kill you immediately. It will take time - maybe a year or longer if Chemotherapy works for some time or one tries other novel therapies like APCEDEN.

[Seasid in reply to binati]

i already had that situation a year ago. PSAD time was 3 months and I just irradiated my prostate. I wanted to add enzalutamide but my RO said that he will not irradiate my prostate if I do that. Therefore I stayed on Firmagon. My PSA dropped six months after radiation to 0.23 and now after a year my latest PSA is 1.7. I did the PSMA pet scan SUV max value of the prostate was 6.5 and the MRI confirmed the cancer in the same place as the PSMA pet scan and the PIRADS score is 5. Still my RO thinks that the cancer in my prostate is a low grade cancer and don't believe that it is a source of the rapid PSA doubling time of 2 months.

[binati in reply to Seasid]

Get a second opinion. We are not doctors to be advising you but just sharing our experience.

[Seasid in reply to binati]

We know that.

[binati in reply to Seasid]

Best of luck.

[Seasid in reply to binati]

Maybe you are curable? I know that you are Gleason 10.

[Seasid in reply to Seasid]

Maybe you had to do the FDG pet scan? And the prostate MRI? As you see above not every cancer is visible on the PSMA pet scan.

link.springer.com/article/1...

[Seasid in reply to Seasid]

Or maybe the Cholin pet scan?

[Seasid in reply to Seasid]

I found this (similar situation like yours):

"This is why IADT v continuous is a controversy. It depends------on a lot of things. I remember several years ago when I was seen at Johns Hopkins with biochemical recurrence 4 years post op, the doc there said he wouldn't start ADT until "I have disease to treat", by which he meant metastases visible under standard scans, which I did not have, and still do not have 7 years later. I am now under the care of an MO at a leading cancer center, and at his recommendation I have been on vacation for 2 years and 7 months. Throughout that period PSA was always <0.01. But now (Nov. 2023) it is 0.3."

healthunlocked.com/advanced...

[Schwah]

arghhhhhhhhh anything good come from what they learned?

Schwah

[Tall_Allen in reply to Schwah]

I think they are giving up on CD28 as the T-cell target.

[fmenninger]

is the the regn press release?

investor.regeneron.com/news...

[Hidden]

While it’s true that prostate cancer is typically immunologically cold it does not mean that the immune system cannot be coaxed into attacking it. Here’s an example of what the immune system can do.

pubmed.ncbi.nlm.nih.gov/366...

Immunotherapy holds great promise even for prostate cancer.

[Tall_Allen in reply to Hidden]

So far, very little promise- but no one's giving up.

[Hidden]

Unknown58 was on a Bite trial for amg509, but his profile and story/posts have gone away. Anyone hear from him?

[Hidden]

So far, very little promise- but no one's giving up.

Tell that to the metastatic patient who is 3.5 years in complete remission after his TIL immunotherapy.

I think it speaks to the very real potential of immunotherapy. Whether we characterise it as very little or great promise doesn’t take anything away from the benefit this patient gained.

[Tall_Allen in reply to Hidden]

TIL isn't prostate cancer. Prostate cancer has been repeatedly found to be immunologically cold. Every cancer is different.

[Hidden in reply to Tall_Allen]

Just to clarify,

TIL stands for tumor infiltrating lymphocyte. The patient had metastatic prostate cancer. His TIL were harvested expanded and re infused along with a check point inhibitor on his 3rd infusion.

[Klunacat in reply to Hidden]

where was this done?

[Hidden in reply to Klunacat]

I searched the name of the lead author.

It appears to have been done in Frankfurt Germany.

Dr Steven Rosenberg at NIH Bethesda Maryland has been doing TIL therapy for several years mainly for melanoma.

Perhaps you could contact him and ask him about the German protocol.

[Believeit]

Does anyone know if Provenge would help with neuroendocrine prostate cancer? Just looking for anything that might be a possibility after chemo (Carboplatin/Etoposide) is completed.

Thanks.

[Tall_Allen in reply to Believeit]

I haven't seen Provenge used - it may be worth a try. Checkpoint blockade has so far shown limited benefit:

prostatecancer.news/2016/12...

[Believeit in reply to Tall_Allen]

Thanks for link. Will update when we know better from scans. 🤞

[mypk]

"As we are all painfully aware, prostate cancer is immunologically "cold." This means the immune system cannot be coaxed into attacking it"

I tend to disagree with that conclusion. I just checked your first link and then continued to clinicaltrials.gov. The REGN5678 trial is still active and recruiting. The details about the two deaths are described here:

ascopubs.org/doi/abs/10.120...

"†2 pts experienced TEAEs resulting in death: 1 from acute kidney injury (not considered treatment-related) and 1 from hemophagocytic lymphohistiocytosis that occurred after DCO (considered treatment-related)."

The other reason is that I'm currently part of the AMG-509 trial. But after just four weeks into it, it's too early to know whether it works or not. My feeling so far is that it does, because one of the side effects is the same bone pain I had during my Docetaxel therapy about three years ago. And Docetaxel did have a clear positive effect for me.

[fmenninger in reply to mypk]

Are we talking the same regn trial and drug as I see TA refers to Regeneron cancelled a clinical trial for REGN5378 not REGN5678. Is this a typo or different drug?

[mypk in reply to fmenninger]

I suppose REGN5378 is a typo, because the following link is about REGN5678. AFAIK a REGN5378 doesn't exist.

[Tall_Allen in reply to fmenninger]

thanks- typo corrected

[Tall_Allen in reply to mypk]

It is no longer recruiting - they cancelled the trial yesterday.

I hope your trial works.

[fmenninger in reply to Tall_Allen]

Do you think the death was possible due to an induced cytokine storm?

[Tall_Allen in reply to fmenninger]

They said "immune-mediated deaths."

[mypk in reply to mypk]

Update:

I meanwhile got 13 weekly AMG-509 infusions and the last CT looks like it is slowly starting to work. At least there is no progression visible anymore in the CT images and PSA is falling slowly.

However, the therapy is no fun. It includes a lot of travel to the study hospital (up to three times a week) and comes with several hardly bearable side effects that last for several days.

[mypk in reply to mypk]

Update:

After 17 weekly AMG-509 infusions the CT and Scintigraphy show a stable disease in the generated images. However, my PSA values are going up and down with a rising trend. It nearly doubled since starting with AMG-509.

[Maxone73 in reply to mypk]

Damn I hope it will work!

[spolyu]

I was advised after 3 years to do Provenge. I have remained stable as per my scans. My PSA seems to bounce around. Right now it’s about 27. My MO said Provenge will give me another year to live. Everywhere I read it says extends life about 4 months. I have heart problems which are under control with medication and 13 years ago I had a stroke. I’m wondering if it makes sense to even consider this treatment. Right now my QOL is good. The MO indicated that the healthier a person is , is when it makes sense to do the treatment. What are your thoughts. Thank you

[Tall_Allen in reply to spolyu]

I don't understand why you wouldn't.

[spolyu in reply to Tall_Allen]

Thank you

[Sunnyday1122]

When you say “cold” does that mean immunotherapy hasn’t been effective to stabilize at all? Or just that the results don’t last very long? My dad is about to start a clinical trial for AMG340 so I am a little nervous hearing this.

[Tall_Allen in reply to Sunnyday1122]

Other than Provenge, immunotherapies have so far been proven to be ineffective for prostate cancer. But we always hope a new clinical trial will work.

[pjd55d]

I did the Provenge in 2018 - Diagnosed in Feb 2017 400 PSA, Lupron knocked it down close to undetectable and after Provenge it was undetectable and has stayed there or close to it. MO and his team think Provenge has helped with my numbers. A positive for me

Best to all

PJD

[wilcoxsaw]

Are the CAR T trials being overseen by Tanya Dorff a part of the ones that are being canceled?

[Tall_Allen in reply to wilcoxsaw]

No.

[K-xo in reply to Tall_Allen]

My husband saw Dr. Dorff in the beginning of August. I took notes when she was speaking about Car-T. (And other trials/treatments) I am extremely quick and efficient with taking notes, so this should be word for word, or VERY close………

“We’re having trouble with screening right now, and the antibody is not working so we want to make sure before we collect T-cells and program them against a target that the cancer has that target. Right now we are struggling with that, so we don’t have any immediate openings on that”

Maybe this has changed since? Idk.

[Tall_Allen in reply to K-xo]

There are 3 trials. There is one CAR-T trials at City of Hope that is listed as still recruiting:

classic.clinicaltrials.gov/...

The others there are listed as active, but no longer recruiting:

classic.clinicaltrials.gov/...

classic.clinicaltrials.gov/...

Maybe she meant those two are not going onto Phase II?

[K-xo in reply to Tall_Allen]

She was def referring to her Car-T trial at CoH. Whether that meant it was not going to phase ll, idk. My intent was to pass this info to the pro. (YOU) I did get the feeling she was somewhat frustrated, but determined to work on a solution. Still, she listed Car-T trial as a potential trial on my husband’s after visit summary, but she was 100% NOT recruiting at that time. (Even though it was listed as recruiting) Maybe something changed since then, or it’s a clerical, update error?

[Tall_Allen in reply to K-xo]

I hope they figure it out.

[Dog_man]

TA: As always, thanks for your posts. Much appreciated.

[Farlo]

Thank you for your continued support via your passed on research and experience.