New Phase 1b (NON-randomized, dose timing) trial of Lu-177-PSMA-617 + Keytruda at UCSF announced

[Tall_Allen]

I know that several patients are looking for a non-randomized trial in the US. This one relies on the theory that the immunotherapy response may be improved by adding a radiotherapy. This theory is discussed here:

pcnrv.blogspot.com/2016/08/...

It is for men with mCRPC who are PSMA-avid (at least 3 PSMA-avid mets) and who have tried Zytiga, Xtandi or Erleada. They allow previous chemo only if it was used while they were still hormone sensitive. There is a single Lu-177-PSMA-617 infusion and patients will get the Keytruda starting 3 weeks before, at the start of, or 3 weeks after Lu-177-PSMA-617. Keytruda may continue for up to 3 years if it seems to be working. They begin recruiting this month. Here are the details:

clinicaltrials.gov/ct2/show...

Also, there is no charge for the Lu-PSMA, Ga-PSMA, or Keytruda. Travel and accommodations are not reimbursed.

[MichaelDD]

My MO at UCSF ...

[Tall_Allen in reply to MichaelDD]

Do you qualify?

[Tall_Allen]

Scott Tagawa at Weill Cornell is testing several radiopharmaceuticals that are chelated to perhaps more specific ligands, like J591 or PSMA-I&T. Perhaps even more promising and less toxic are non-chelated radiopharmaceuticals. Progenics will be taking I-131-MIP-1095 into a phase 2 clinical trial, probably at MSK at least, but it is not available yet:

pcnrv.blogspot.com/2018/10/...

[tango65]

This is another one in the pipeline,

cancerres.aacrjournals.org/...

[tallguy2]

This is good news...a wave of trials and treatments coming our way! Thanks for posting.

[henukit]

Yeah, right, nuke it!

[Tall_Allen]

Here's an article about the upcoming Th-227-PSMA-antibody clinical trial:

pcnrv.blogspot.com/2018/10/...

U237 is a beta-emitter

[cesanon]

Dumb question: What is "PSMA-avid"?

[Tall_Allen in reply to cesanon]

Lu-177-PSMA-617 only works on cancer cells that express prostate cancer membrane antigen (PSMA). So PSMA is the true target of the drug. Without it, you would just be taking a dose of radioactivity with no particular place to go. Some (rare) types of prostate cancer do not express that protein. They check first with a Ga-68-PSMA-11 PET scan that detects whether mets express PSMA (avidity).

[MJCA in reply to Tall_Allen]

Hi Allen,

I spoke with UCSF, this changed my conception of a “clinical trial”. This would cost me $4K-$6K. I was given the CPT codes to check with my insurance. I get really irritated speaking with insurance.

[cesanon in reply to MJCA]

If you have the money, it is worth it. I've spent more money on plumbers.

If you don't have the money that is another discussion, but one we can't really have in this forum, as the idealogical haters will not permit others to express opinions or discuss facts contrary to their emotion based belief system.

[Tall_Allen in reply to MJCA]

Dr Agarwal told me just yesterday that there is no charge for any of the drugs. The procedures are covered by insurance. Who did you speak to?

[MichaelDD in reply to Tall_Allen]

Great doctor...

[MichaelDD in reply to MJCA]

Did you ask for a quote if you self pay?

[Tall_Allen in reply to MichaelDD]

There are NO out-of-pocket costs for the drugs.

[Stegosaurus37]

I went through the consent form for Lu-177 yesterday at OHSU. Thinking about it later, I have serious concerns. We were told my wife would have to sleep in a separate bed for the study duration and I would be given a dosage card which I would have to carry since apparently the study drug can set off security equipment. My wife is worried about whether we'd need a new bed afterwards, but I have a more serious concern.

Nowhere in the Consent Form does it address the risk of my getting radiation sickness, yet it seems from the above that it is a very serious risk.

So: does anyone know what the dosage is? How many millicuries per hour are we talking about? What has the German experience been? (The OHSU people didn't seem to be familiar with the German trials, which is another concern.)

Since it was "Standards of Practice" that got me into this mess, I don't have a lot of faith in the medical profession and try to get everything independently confirmed.

Thanks for any help!

[Tall_Allen in reply to Stegosaurus37]

You can call to find out the dose they administer. Because it only attaches to prostate cancer cells, it does not cause much tissue toxicity. Beta particles are very weak and do not make it outside of the body. Lu-177 is also a gamma emitter, and that radiation does penetrate, but it does not harm tissue. So far, the toxicity has been acceptable (none above Grade 2) - mainly salivary glands. Although it is eliminated through the kidneys, there has not been much renal toxicity. It is difficult to sort out whether any blood toxicity occurred because of the radiopharmaceutical or the late-stage cancer (which affects bone marrow) - that's one reason why a randomized trial is needed. Toxicity is discussed in these articles:

pcnrv.blogspot.com/2017/09/...

pcnrv.blogspot.com/2016/08/...

pcnrv.blogspot.com/2016/10/...

[Dayatatime in reply to Stegosaurus37]

True story - I live stateside on the US / Canada border and often fly out of Ottawa, Ontario when traveling to yearly postoperative follow up scans at The Mayo in MN. When going through customs while in my vehicle I set off radioactive alarms and have to go in to explain, get checked for level of radiation and vehicle searched. It is never an issue but first time it happened I was shocked radiation was detected while in my vehicle only from CT and bone scans. Customs told me it happens frequently.

[Tall_Allen in reply to Dayatatime]

Bone scans use Technetium 99m, which is mostly a harmless gamma emitter. It has a half life of 6 hours, so it is undetectable in two days. CT scans are just external X-rays that leave nothing inside, and are undetectable by airport screeners.

[cigafred in reply to Tall_Allen]

Several days after a Technetium bone scan I set off an alarm when entering the Whitehouse. I explained, and they sat me down next to a big box that took a few minutes and then reported its agreement.

[Jbooml]

You are one hell of a guardian angel....wish you were my doc.

[Stegosaurus37]

That was my assumption too until they told me I shouldn't sleep in the same bed with my wife. Why do they think she might be endangered? And that they think I might set off security alarms? I've called the study people with these questions and I'll make a post when they get back to me.

My evaluation criteria are (1) what could it do for me? and (2) what could it do to me? If there is a danger of radiation sickness I don't give a damn of how effective it might be against the cancer. The toxicity is something I understand and it is an acceptable risk. My kidneys are in great shape.

[Tall_Allen in reply to Stegosaurus37]

I think they are just being cautious. You set off security alarms because of the non-toxic gamma rays. I don't know what you mean by "radiation sickness." As you see, toxicity has been low and limited to certain organs (salivary glands, tear ducts) and is transient.

[Stegosaurus37]

"Radiation sickness" check out Hiroshima and Nagasaki. I used to sit nuclear alert in the Air Force so have been exposed to some studies of effects. They aren't pretty reading. Also luminous watch faces used to be hand painted with tritium paint. The workers would sharpen their paintbrushes with their tongues with bad results. Needless to say they don't use tritium for watch faces now. The point is, nuclear materials are never safe and it is a grave mistake to take anything regarding them on trust.

[Tall_Allen in reply to Stegosaurus37]

I can guarantee you that the amount of Lu-177-PSMA-617 injected will not cause radiation sickness like in Hiroshima and Nagasaki. They have been giving Xofigo, a much more powerful alpha emitter for years and there have been no reports of such a thing.

[bobdc6]

Do you know of any results of LU-177 treatments? How about from Germany? Do you think it's worth using on a first recurrence of a G 4+5 previously treated with proton and adt?

[Tall_Allen in reply to bobdc6]

Click on the links I provided above.

[bobdc6 in reply to Tall_Allen]

Thanks, looks like it has a way to go before it's widely used.

[Tall_Allen in reply to bobdc6]

Not too long for advanced mCRPC - the VISION trial will have results in 2020. I'm not aware of any trials for early recurrences.

[bobdc6 in reply to Tall_Allen]

Thanks.

Bob

[Moespy]

Allen,

I had a biopsy Monday at NIH on the "Bright Spot" found on my PSMA Scan in a pelvic lymph node. My question is why can't Lu-177 and/or other PSMA targeted therapies be used on high risk/castrate naive patients in the hopes of an early cure?

Thanks, Jim

[Tall_Allen in reply to Moespy]

Maybe, someday. Right now, there are studies looking at the "natural history" of PSMA. It's been found in some high risk prostate tumors - does it appear when the cancer is GS6? GS9? metastatic only? Some reports show an increase with ADT, some do not. There are only a few clinical trials (NIH, UCLA, etc.) that are allowing PSMA PET scans on high risk cases. Also, because PET/CTs can only show larger tumors, they do not show everything that's there.

Does the cancer develop PSMA-resistance? (probably) What percent of metastases are killed by the radiopharmaceutical? Does its action depend on the the abscopal effect? (probably) and if so, would it work better with some kind of immunotherapy? (probably) For those who are high risk, or N1M0, is it more or less curative than brachy boost therapy + ADT or RP+ePLND+SRT+ADT?

It's easier (about 5 years) to prove efficacy (improvement in overall survival) in men with advanced PC. It will take trials with a 15-20 year follow-up to prove efficacy for localized PC. Long-term safety will have to be learned also.

[Moespy in reply to Tall_Allen]

Thanks for the detailed response.

Appreciate it.

Jim

[abmicro]

Here is my report on LU177 vision trial. Stanford is swamped and not even ready to treat. UCLA may be full now but I was very lucky to get into UCLA 3 months ago and get randomized for the drug. PSA dropped on first dose. Had 2nd dose and waiting for pelvic pain to drop. They said pain should drop soon. I have not set off any TSA alarms, and I am not taking Zofran for radiation nausea because I dont have any nausea. Separate beds and bathrooms last only 1 week because the radiation cools off due to the short half life. The frequent scans every 10 to 12 weeks will be an inconvenience and they will fly me back for those. Able to do some of my standard labs like CBC CMP and others at UC Davis so I dont have to fly back to UCLA every 2 weeks.

Regarding the new trial LU177 with Keytruda at UCSF: glad they are finally combining therapies. Much more effective I am sure. Non-randomized? UCSF will be swamped with people wanting to get in. Sounds like an excellent trial.

[BruceSF]

Dr Aggarwal will be speaking at the UCSF program June 8 (see my post above)