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Tony Loves

AMG160 -new phase 1 trial using immunotherapy.

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Tony Loves

Hi guys.

I'm a guy that has been fighting my cancer since 2009.

I have had pretty much all the treatments & am at the stage were I didn't qualify for the "Prince trial" Lutitium 177 & Keytruda at St Vincents in Sydney, as my cancer cells are not expressing enough PSMA on their surface.(70% qualify) unfortunately I'm in the 30% that don't(which sucks)

I've been referred to another oncologist to look at a stage 1 trial called  AMG160 which is run by the big pharma company Amgen who also make Xgyvia which many of you may take to strengthen bones.

Anyway their is very little on line about it.

Its a phase 1 study evaluating the safety, tolerability, Pharmacy kinetics & Efficacy of (PSMA) Half life Extended(HLE) Bispecific T- Cell Engager(BiTE) AMG160 in subjects with (metastatic Castration Resistant Prostate Cancer.

Another arm of this study is they are combining AMG160 with Keytruda.

That's a bit of a mouthful but I copied from Consent form.

So basically can anybody tell me anything about this as I'm going for a interview this week.

Kind regards

Tony L

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Admin

Tony

I am not a doctor, so I understand I may have this all wrong.

But I understand that each AMG160 has two 'grabbers' - one on each end.

One grabs an immune system attack cell (cytotoxic T lymphocytes (CTLs) ).

One grabs PSMA. (PSMA is found on the surface of prostate cancer cells).

So basically AMG160 drags a killer immune system cell to kill a prostate cancer cell.

It seems to me that it would have the best chance of working if your prostate cancer expresses a lot of PSMA.

But you say this is not the case.

Your doctor should help you understand exactly what is expected to happen.

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alanbarlee

Wow, Tony - you're certainly a trailblazer! Best of luck with the Amgen Phase 1: I'm sure you'll get well looked after on the trial.

 

Sorry that you dipped out on the L177/Keytruda trial. Have you been down the gene-typing track? BRCA1/2 and ATM mutation testing is now more available in Oz (e.g. Peter Mac in Melb), and there's some good data on PARP inhibitors (e.g. Lynparza) that can help, especially with BRCA2 deficiency, which can occur in 12-15% of metastatic men. Trials combining PARPi and Keytruda are also recruiting, again selecting other specific gene mutation men for targeted responses.

 

Keep us in the loop - and good luck from all of us!

 

Cheers,

 

Alan   

 

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Tony Loves

Thanks Alan,heading to Sydney tomorrow as were on the Sth Coast NSW.

I'll find out a lot more tomorrow,

That Lynparza & Keytruda trial could be interesting as St Vincents sent my blood to Singapore for the Prince-Lutitium trial and I believe I have 1 strand of Brachy 1 or 2 but for some reason was missing second side to Gene.Apparently it is rare!!

Do you know where the new trial is for the Lynparza & Keytruda is on at.Melb or Syd & what hospital??

Unfortunately I haven't got a copy of the report,its just what my oncologist explained briefly

Anyway hopeing for positive discussions tomorrow regarding BiTE immunotherapy.

I'll keep you in the loop.

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Tony Loves

Thanks Admin for your easy to understand explanation.

I agree with your explanation from the little I can find on the net about grabbing a immune cell & a cancer cell,basically making a bridge or like a missing electrical connection.

I have asked them about the level of PSMA as this was the reason I didn't qualify for the "Prince" trial using Lutitium 177 & Keytruda but they told me this wouldn't be a factor as all cancer cells express some PSMA.

Mine just didn't have enough for the Lutitium.

I guess I'll find out tomorrow.

Thanks for your interest & explanation.

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ardee

There's a similar Regeneron drug that Charles Drake is trialing at NY Presby - REGN5678. It grabs the cancer cell with one arm and a T-cell with another, pulling the T-cell into the cancer cell. Jonathan Simon, CEO of Prostate Cancer Foundation has called this the most exciting research out there!! The ID trial number is NCT03972657. I don't know how the REGN drug captures the cancer cell ..... it looks like the AMG 160 does that by attracting PSMA.

 

Tony ..... my question to the trial coordinators - in particlular the Aussie PI, would be to drill down on how much PSMA you need to express. If you are not sufficiently PSMA avid for Lu177, that could be a concern. Since this is a Phase 1 , they are probably looking at how much PSMA it takes. YOU have to keep these researchers honest - as Nev will tell you becasue he was in our US virtual group last night and heard the discussion (you can listen yourself here https://ancan.org/hi-risk-recurrent-advanced-pca-men-caregivers-recording-may-4-2020/ ) these buggers have an innate conflict of interest because they are always looking for fresh meat!  You can't afford to be messed around in a trial for which you may not be the best candidate.

 

Not saying this is the case - but I am saying that your lack of PSMA raises a flag I know I would want to follow. 

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Allyn

Hi Tony

Words of wisdom to date from the guys as always and your situation is not dissimilar to the position I found myself in 7 months ago. I am still on the journey so too early to know where I am at but I'll share my logic 

My PSA had been doubling every 2 months for over a year and I had 5 Ga68 scans over that time and none showed any Ca outside of the prostate. So at my pushing I was taken off of Enza in November for a possible immunotherapy Trial out of China

My concern was that our mates here had advised that all Pc's are different so what made the Onc think this trial suited me

So I have now had somatic and germline testing from my original biopsy 

Turns out I have two CDK12 variants HRD and a germline FANCI mutation which is only a C3 mutation

In short I am different (as we all are I guess)

So I was looking for appropriate Trials and came upon the MK-7339-007 Trial of the combination of Olaparib/ Pembrolizumab. For this I needed measurable disease which I had been told over and over I had none. Trial MD asked for an MRI and guess what... I had a 6x7 cm lesion at base of bladder to date unseen in Ga scans

I am now on that Trial out of Gold Coast but early days atm

I feel that I know a lot more about my Pc and can make more informed decisions in fact quite different decisions to what I would have made 6 months ago

Hope this can help a bit

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alanbarlee

Hi again Tony,

Allyn has provided you with details of a PARP/immuno trial that you might raise with your medonc (Good to hear that you're back on track in chasing down the cause of your stubborn PSA rise, Allyn - good luck with the trial!)

 

Allyn's imaging experience also brings home an important point with PSMA-PET/CT (gallium) scan. While this scan is clearly more sensitive and specific than the traditional bone and CT scans, There is a significant proportion of PCa men (possibly up to 30%) whose tumours don't express PSMA, and who are therefore not suitable candidates for PSMA/PET scans. Other scans are therefore needed if PSA is rising but PSMA/PET is negative (and even if it is positive, a scan using a different linking agent to the prostate cell membrane is usually specified). 

 

A common backup scan is 'FDG' PET/CT, and there are others in the pipeline, like an F18-containing ligand that is currently on trial.

From Allyn's experience, mpMRI remains an important scan. This is well-proven for detecting tumours within the prostate, and the location of Allyn's tumour (located just below the bladder, where the prostate sits) with MRI suggests that its use might extend further.

For situations like this, it might be worth raising the possibility of adjuvant radiation - especially SABR (stereotactic = highly targeted / high energy radiation), which may both directly kill tumour cells as well as increasing the effect of systemic therapies by activating the immune system.

A few thoughts for discussion with your medonc  - who seems to be on the ball.

Cheers,

Alan

 

  

 

  

 

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Patrick Turner

Peter Mac in Melbourne has been investigating why 30% of men don't get a benefit from Lu177, and I assume that is where PsMa Ga68 scans show that the man does have enough PsMa expression to get Lu177 to gathered at their Pca sites in PG and mets.

I met one man while having Lu177 who wasn't doing well on Lu177, and Psa about 200 and rising and with pain in hips joints from bone mets.

But he had enough PsMa expressions. Professor Louise Emmett was looking after the atomic ( Lu177 ) therapy patients at Waratah Hospital in Sydney on my 3rd shot of Lu177, and she suggested strongly I take Xtandi, enzalutamide, because that increases PsMa expression and makes more Lu177 gather at met sites to make the Lu177 do more than it would without Xtandi. Her idea was that because I'd had chemo ( which failed ) before Lu177, the chemo would have re-sensitized my Pca to more suppression by enzalutamide or arbiraterone, ( Zytiga ), and I'd have increased PsMa expression. OK, so I began taking enza right after 3rd Lu177 shot, and I doubt it did much, but enza was well into my system before my 4th Lu177 shot May 2019. I am still taking enza. PsMa scan in August 2019 showed bone mets healing and no soft tissue mets, and Psa had continued to reduce from 25 before I began Lu177 to about 1.6, and by November 2019, Psa was 0.32, but that was a nadir, and since then Psa has now risen to about 5.0, and I see my onco in 28th this month about getting yet another PsMa scan to see if more Lu177 is likely to work again like the first lot did. Peter Mac Professor Hocking has said repeat doses of Lu177 may be used a couple of times so mean time for life extension will move from 14 months ( which I have just had ) to up to 5 years. Whether ennza is still working is doubtful because its effectiveness has mean time of working for maybe less than a year, and I's taking it for a year, so its effect could be failing, but nobody knows if it is increasing my PsMa expression so that more Lu177 will be most effective if I have more of it. I am afraid of having Pca that now does not express PaMa, and have to fall back to taking olaparib PARP inhibitor, and efficacy is low, because once the common treatments fail to work and you move to relying on blood analysis of DNA and trying to match something such as keytruda to treat Pca, its all rather "experimental" and I've seen friend die fast where the analysis and treatment matching failed dismally.

I have been fighting Pca since 2009 diagnosis with Gleason 9, Psa only 6, at age 62, which turned out to be inoperable. No spread was found, but I expect I had hundreds of tiny mets which could not be seen. ADT suppressed all my Pca until 2016, and I had more IMRT to PG, with 6 months on Cosadex added to ADT, and that gave 6 months and Zytiga gave 8 months, and 5 x chemo shots did nothing it seemed.

But having Pca for such a long time means likelihood of Pca mutation is very high. I have history of having cancers in my father's side of family, his mum died of Brca or Oa, not sure which, then dad died of melanoma at 60, one of my sisters died of Oa at 60, and other sister got Brca at 64, but got diagnosed just early enough to have good outcome after having double mastectomy plus hormone therapy for 5 years. She's survived OK at nearly 76, but mental effects on her were not good. 

So I could see my turn to get cancer was coming, and had yearly Psa tests but I had lots of Pca making a low Psa. I should have has PG removed in 2004, when Psa was about 3.0. At present, many men are being treated much TOO LATE because the threshold for Pca examination is only recommended when Psa > 5.0. Men who are probably never going to have Pca bothers have Psa 0.7 at 40, 1.0 at 60. My cousin of 74 has Psa of 1.0. It has not risen for years.

But many of us here find we have Pca despite the tame prevention methods of the medical system. Its normal for many of us to have a succession of treatment that result in Psa moving up and down like as one treatment is done after the other, and some point in time there just isn't anything that works. If I had not had Lu177, I'd be in palliative care now with a Fentannyl slow release insert to deal with pain.

But instead of that outcome possibility, I am cycling 200km a week at nearly 73yo, and in good average speed, I have no pains, no co-morbidities, so docs at Canberra Hospital think I am healthiest stage 4 cancer patient they have ever seen.

But my Psa is rising yet again, and all I can do to is wait a little longer before another PsMa scan, and if that shows very low PsMa expression, then I guess I'll have blood analysed and maybe samples of tumor analysed, and then trust that the experts will work out a fix most likely to work. The real chance seems low that anything might work where Lu177 cannot be used. I've survived 10 years after diagnosis, never knowing if I'd live another year. 

My doc said I ought to try Cabazitaxel. But Docetaxel failed, and Caba has only slightly marginal better outcomes, and maybe worse side effects of "dulled lower leg function" that I still have due to only 5 shots of Docetaxel, about 2 years ago. 

I have little to say that might be a real good remedy for Tony right now. But he may see something worth knowing if he compares my history with other mens' histories. Some of us are able to do this, rather than just be passive about whatever the medical experts we happen to meet will recommend. 

Meanwhile, Canberra's frosty mornings have begun and I don't get on the bike until after lunch when its warmed up enough. I did once get out on mornings with -3C to cycle 17km to hospital to see my oncologist. I've watched him slowly get grey hair since 2010. Being very fit with BMI 22, waist < 90cm, resting HR < 50 probably has reduced the severity of side effects of all the many treatments I have had so far. I have had a very good QOL despite the Pca, and during this lock down time due to C19, many more ppl are out on their bikes to stay fit, or get fitter, while unemployed, but its still been years since anyone over 65yo has overtaken me just riding around the roads and cycle paths here. 

I am on the right sort of diet, so there's little more I could do to combat Pca, except try to pick the best of what docs can offer based on science. AFAIK, Lu177 would be available again in Sydney at Waratah Hospital at Hurstville, and about when I probably will need it within 2 months.

I don't know yet how C19 has affected such radio-nuclide treatments.

There's no reason to give up yet.......

Patrick Turner. 

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