Decision time Lutetium or AM509

[MarkEmrys]

M1, five bone lesions, mCRPC with PSA now doubling each month (currently at 1.7), after failure of abiraterone. I've been offered a "slot" for two clinical trials: AMG509, a bi-specific T-cell engager, and a new version of Lutetium therapy, called Lu-DOTA-TLX590-CHO (which they say is novel, and seems to be a new version of J591). I also have the option (outside of clinical trial) of 177Lu-617 (which is recently approved in US), possibly with concurrent enzalutimide as radiation-sensitiser.

Diagnosed 2019 and have had docataxel and ADT upfront, Abiraterone, EBRT and stereotactic on progression. Now solely on goseralin and prednisone.

Would appreciate any comments, experiences, or questions. As many of you would be aware, these decisions are difficult.

Cheers (from Cairns, Australia)

MarkEMrys

[PGDuan]

Hi Mark, Good to hear you have options, but alas I'm unable to offer any informed advice. Hoping you'll hear from others with first hand experience or insights.

[MarkEmrys in reply to PGDuan]

Hi PG DuanTerrific to hear from you anyway.

cheers

MarkEmrys

[Ramp7]

We are the same age. My doubling time when Lupron and Zytiga / 5mg prednisone failed was 3 months. To date I have completed two infusions with LuPSMA617. PSA has dropped from 8.1 to 1.8 as of a few weeks ago. Scheduled for a total of six infusions. To date well tolerated. No noticeable side effects. Still on Lupron, Zytiga was dropped.

[MarkEmrys in reply to Ramp7]

Hi Ramp7Good to hear you are doing well on LuPSMA617. Great PSA drop. Can you tell me the cost of each infusion, and whether covered by your medical insurance? Cost is $10k per infusion here in Australia.

cheers

MarkEmrys

[Ramp7 in reply to MarkEmrys]

I entered a trail study here State side prior to the FDA approving its use. So the LuPSMA617 is provided by Novartis at no cost to me. I have to abide by their testing requirements and follow up.

[MarkEmrys in reply to Ramp7]

Hi Ramp7You are very fortunate. Hope it keeps working for you.

cheers

MarkEmrys

[Ramp7 in reply to MarkEmrys]

I count my Blessings each day.

[joeguy in reply to Ramp7]

Which Novartis trial did you get into? I was looking at the PSMA Fore trial a few months ago, but was told it was on hold due to supply problems with the drug. We have since managed to get my PSA below 2.0, so I am not currently eligible anyway, just curious.

[Ramp7 in reply to joeguy]

I just checked my paperwork, it does not say specifically the Trial number. When I initially contacted Dr. Beltran at Dana Farber my PSA was 1.1 but rising, until it allowed me to be accepted. Continued good news on your PSA.

[joeguy in reply to Ramp7]

thanks....... they didnt mention anything bout shortages of the LU177 drug?

[Ramp7 in reply to joeguy]

Interesting that you should mention that. From reading here, shortages was mentioned. At my latest infusion 3 weeks ago, I questioned the Admin. about shortages. She assured me that there will be no issues.

[joeguy in reply to Ramp7]

good to here....... I had heard the drug comes from somewhere in Europe typically. Glad that its becoming available again.

[Ramp7 in reply to joeguy]

Italy I believe.

[Javelin18]

I think one way to look at the choices is the relative maturity if the testing. Lu-PSMA 617 has the most thorough testing of the three. There have been discussions on the forum of doctors in Europe combining with enzalutamide with success.

It's always difficult to know which trial might work for an individual. I had other cancer growing while Lu-PSMA617 was killing cancer in me. I ended up stopping the therapy and am waiting to start a CAR-T trial in the US. I'm also considering AMG509 if I get worse waiting.

Not sure I'm being much help here, but there seems to be a lot of luck in picking trials, hoping that the one you pick is effective for you. Part of the CAR-T and AMG509 trials is testing the patient to make sure their biopsy sample expresses the antigen that the treatment targets. At least that's a way of knowing when a trial drug won't work.

[MarkEmrys in reply to Javelin18]

Thanks Javelin18Take your point about maturity of Lu-PSMA-617, and indication that Enzalutamide seems to enhance Lutetium. Now looking at doing the Lu-DOTA-TLX590-CHO clinical trial (its a dosimetry study with 2 infusions), if I can follow with some (up to 3-4) LuPSMA-617. The TLX590 uses an antibody , while LuPSMA-617 uses a small molecule.

I might be misguided here and will need to discuss with relevant MOs. While the AMG509 looks good, I would have to move to another city to take part; while a slot has been offered, they are willing to wait list me for next phase.

Sounds like I am trying to not make a decision!? and keep all options going...

Its day 1 of the decision process...

Cheers

Mark

[Tall_Allen]

Towards the end of this article are many PSMA-targeted therapies in clinical trials (several in OZ) that you may want to discuss with your doctor:

prostatecancer.news/2019/12...

I would decide between AMG509 BiTE and PSMA targeted therapy based on relative avidity of PSMA and STEAP1 (based on IHC quantification of STEAP1 and PSMA on biopsy tissue). I'd also get an FDG PET scan.

Of the 2 radioligands, J591 is probably less toxic.

[MarkEmrys in reply to Tall_Allen]

Thanks AllenYou seem very well informed. Are you in the medical field?

cheers

Mark

[Scout4answers in reply to MarkEmrys]

T Allen is indeed well informed, and an asset to the forum.

[Boonster in reply to MarkEmrys]

He's the greatest! We're lucky to have him on this forum.

[MarkEmrys]

Hi T AllenUnfortunately biopsy of bone is proving difficult. First one was contaminated. Early Feb biopsy is apparently a ‘tiny’ amount of tissue. They’re trying a T1500. Apparently any results take ten weeks.

[MateoBeach]

TLX590 if an antibody ligand like J591 has much stronger binding to PSMA. Can use lower doses of Lu177 and less toxicity (except marrow suppression). If either trial is open label and pays for the treatments then that would be compelling. Absent sufficient and positive biopsy tissue the Lu with the antibody ligand is compelling. I am coming to Perth in May for J591 treatments in Perth. Only two required, two weeks apart. For you, an FDG PET is a very good idea first for concordance.

[MarkEmrys in reply to MateoBeach]

Thanks MateoBeachSounds like you are coming to Perth for the same trial— prostACT. TLX591 is same as J591 — but a newer version, I understand. Dr Nat Lenzo in Perth? Its multi centre — I’m looking at ProstACT in Brisbane under Professor O’Byrne. Two infusions two weeks apart, starting in May. Do you have any sources/links to more information on its tighter PSMA binding?

Cheers

Mark

[MateoBeach in reply to MarkEmrys]

This is worth considering with J591 or similar mAB. Have to accept bone marrow suppression from longer circulation time. May well require transfusion. I have decided to accept this.

auajournals.org/doi/10.1097...

[MarkEmrys in reply to MateoBeach]

Thanks for that link Mateo. OS 5 months longer with Lu-J591 compared to lu-617 but no difference on further analysis and dose dependent it appears. Expect side effects would be well managed for J591 as part of clinical trial protocols. Wondering if possible to do Lu-617 after Lu-j591.

[MateoBeach in reply to MarkEmrys]

Yes in 617 down the road if further progression and still PSMA avid. Had a consult with Yong Du on London 2 days ago and asked that. But he does not have J591 in the UK yet due to not approved there. He says the Ozzie docs are “lawless”. 😆 I’m not in the trial just cash pay as I’m a Yank.

[Hailwood]

I have no valid advice yet as I'm not at that stage but would likely go with any trial that was at least in its second/third round of tests. Good luck with your decisions

[MarkEmrys in reply to Hailwood]

Thanks HailwoodDefinitely would rather be in phase II or III. Seems TLX591 is well studied -- this trial is (apparently) a newer version. I am being assessed for this, and will find out more and post.

Decided not to go ahead with AMG509, even though Ive been offered a slot. 70% extreme fatigue and weekly infusions for as long as it is effective. Have been put on wait list for when that trial is further developed.

cheers

MarkEmrys

[j-o-h-n]

T_A definitely knows his stuff.......... which I taught him....... (humor too)......

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 03/29/2022 6:33 PM DST

[slpdvmmd]

Don't have lot to offer in your decision process. But during the course of my disease I spoke with a number of Australian's and seems like compassionate use is more liberal in Australia and more options for radioligand are available than in the US. My sense is you are in good hands. Wish you well.

[MarkEmrys in reply to slpdvmmd]

Thanks mate. All the best.MarkEmrys

[Graham49]

I presume you had docetaxel some time ago. Your cancer is growing fast and docetaxel is best for fast growing cancers. It might be worth discussing another round of docetaxel if you were not too badly affected last time.

[MarkEmrys]

Thanks Graham - yes had docataxel up front. Clinical trial starts in 6 weeks. Two infusions of a new radio pharmaceutical. Will look at chemo after that. Please share any info you have on fast growing cancer.

[MarkEmrys]

Thanks—now going ahead with lutetium617 in Australia

[MarkEmrys]

Hi Roy — it’s $AUD10,000 per infusion.