“Tests and Treatments for Rick Stanton”

“Tests and Treatments for Rick Stanton” [#3] April 6, 2022 Brad Power Meeting Summary Advanced prostate cancer patient Rick Stanton shared details on his testing and medical history, treatment options being considered, and the tests he would like to see to inform his future treatment decisions. ●Medical history: Rick shared a table with his PSA measurements and treatment history.

His PSA is currently under control, and he is looking to have his next treatment ready to go. ●Treatment options: Rick listed the treatment options that have been recommended to him. Dr. John Laird suggested that trying chemotherapy combinations in the lab of Bob Nagourney at the Nagourney Cancer Institute would have a greater assurance of efficacy (80-90%) than clinical trials (15%).

Rick Davis endorsed treatments with more evidence, and recommended that Rick revisit his initial diagnosis, as well as considering Pluvicto (PSMA-targeted radiation nanoparticles). ●Tests requested and analysis desired: Rick has requested IHC stains that will provide indications on his likely responsiveness to immunotherapies.

He is offering his extensive medical data to anyone who would like to hack on it. We continue work on “right to see” – finding ways for patients to be able to access data from “research use only” tests run on them.

Requests ●Please let us know if you know anyone who might be interested in being a principal investigator, or any potential funding organizations, for an observational feasibility study on providing data from emerging (research use only) tests to patients to guide their prostate cancer treatment decisions (“right to see”). ●If you would like access to Rick or Brian’s data, please contact them.

●Please join our online discussion forum for 24/7 conversation.

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You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Tests and Treatments for Rick Stanton” [#3] Meeting Notes Brad Power: There are three agenda items we plan to cover in this meeting: 1.An update on our work on “right to see” - the idea that patients should have access to “research use only” data that is run on them. 2.

Rick Stanton is going to lead us through his treatment situation, his history, and the decisions that he is facing now, as a setup for the issues facing people like him with advanced prostate cancer. 3.Rick will share the data that we have on him and Brian McCloskey and the additional tests he would like to see run.

ough his treatment situation, his history, and the decisions that he is facing now, as a setup for the issues facing people like him with advanced prostate cancer. 3.Rick will share the data that we have on him and Brian McCloskey and the additional tests he would like to see run.

“Right to See” We spoke with Nik Schork, Peter Kuhn, and Marty Tenenbaum in the past week about various ways to get around the roadblocks to patients having access to data from “research use only” tests run on them. One workaround is to have an IRB (Institutional Review Board), as Nik Schork talked about in our last meeting.

Nik described in our last meeting how he helped get an IRB-approved protocol for Rick Stanton. So one path is to broaden or expand that as a template for others to use. Another workaround is to set up an observational feasibility study, which is a research study with a lower barrier to set up than a classic randomized clinical trial, which is prospective, expensive, and slow.

We are working to find principal investigators and organizations that would fund such a research activity. If you know anyone who would potentially be a PI or an organization that would want to fund that kind of work, please let us know.

Rick is also trying to go through standard channels and a CLIA-certified lab to get the advanced testing he would like through City of Hope, where he is being treated by Tanya Dorff, and where they have access to his tissue. Rick Stanton: TGen is moving ahead with approvals to work with Akoya and Enable. I can’t say for sure because Akoya and Enable don’t want to talk to a patient.

They want to talk to TGen, which has the protocol in place. I’m boxed out. I get a little update that things are moving ahead. I’m very excited about that because I would like to be the first of many. I’d like this to be available to everyone who has the means. It’s fairly modest, I think a few thousand dollars. It’s getting closer.

Introductions of New Participants Rick Stanton: I’d like to hear from some of the people I see on this call whom I don’t know. Could you please introduce yourselves?

“Tests and Treatments for Rick Stanton” [#3] Dr. John Laird: An MD focusing on complex cancer patients and integrative treatments, recently relocated to Asheville, North Carolina. Saed Sayad: An MD now focusing on AI, professor in the Computer Science department at Rutgers. Alex Feltus: Biochemist, biomedical, genomics, professor at Clemson, crops, high end computation.

Chandra Kota: A medical physicist working in new radiation treatments. Currently working at Yale and looking beyond my day-to-day job and seeing how I can help patients with advanced radiation treatments. Heather Messerly: At Certis Oncology in San Diego, creating PDx models using mice of patient cancer tumors to test different treatments on them to see which ones work and do not work.

I’m not a scientist. Patient manager. Learning by sitting in. Happy to step in and help.

d radiation treatments. Heather Messerly: At Certis Oncology in San Diego, creating PDx models using mice of patient cancer tumors to test different treatments on them to see which ones work and do not work. I’m not a scientist. Patient manager. Learning by sitting in. Happy to step in and help. Jan Sobieralski: A patient with castration-resistant prostate cancer.

I just asked my doctor if I could get Leutetium 177 (discussed in our last meeting), and they said “no”, because I have to be castration-resistant and have had the Taxol treatment, further along in my journey. Rick Stanton Case Rick Stanton: To start with how I’m doing. I just completed six rounds of docetaxel.

In my last round I had an 80% dose since I had developed some tingling in my fingers (neuropathy), and I’m a guitarist. When I got my infusion, they also took my PSA, and I learned that my PSA had gone down – not a lot, but it did – from 2.6 to 2.4. The time before that it was 2.4, so I’m bouncing around 2.5. My cancer is being controlled. I expect to get another round of chemo.

At the start of my chemo I was advised that I would have six to ten rounds. This is in an Arcus clinical trial. I was randomized to the docetaxel arm, not the arm with a PD1 inhibitor and an adenosine inhibitor from Arcus I had hoped to get. Sandy Liu of UCLA is the leader of this trial and my treating oncologist. The folks at Arcus are my friends from when we worked together at Amgen.

They are a very good small molecule company. I hope my decisions will be informed by an IHC (immunohistochemistry) stain at a minimum.

“Tests and Treatments for Rick Stanton” [#3] These are four tumor slices. This is a CD3 stain, that is looking at T-cells: CD4, CD8, and Tregs (regulatory T-cells). The brown pattern in the upper left tells you that this tumor is loaded with TILs (tumor infiltrating lymphocytes), which means it is “hot”. On the right you see that it is “cold”, T-cells are not infiltrating this tumor.

On the lower left if you did an RNA-seq, you would think you had good infiltration, but the moat of exclusion means there is immunosuppression. In the lower right you see a low amount of infiltration, though they are there. The reason I bring this up with the four states is that this IHC staining or spatial analysis would influence your selection of an immunotherapy.

If you have low infiltration, either you need to do a prerequisite or hope for a miracle.

“Tests and Treatments for Rick Stanton” [#3] Brad Power: Which do you look like? Rick Stanton: I don’t know. I’m waiting on IHC - this stain. I asked Tanya Dorff to order it for me, and she agreed. I would call this spatial analysis. Akoya, Enable, and NanoString all do very deep queries using advanced technologies which are “research use only”. I want to do this with IHC, which is more standard. I hope that I will be in the upper left.

asked Tanya Dorff to order it for me, and she agreed. I would call this spatial analysis. Akoya, Enable, and NanoString all do very deep queries using advanced technologies which are “research use only”. I want to do this with IHC, which is more standard. I hope that I will be in the upper left.

If you’re in the upper right, cold, with no tumor-infiltrating lymphocytes, PDL1 blockade inhibition is not going to work because there are no T-cells to modulate. Dr. John Laird: As you said, with the upper right hand result, it would be a waste to try immunotherapy. Prepping that microenvironment would be key.

There is a group, not set up commercially, called Consultative Proteomics at the University of Texas, led by Dr. Robert Brown, that I’ve used. They do proteomics, IHC stains, 20 or 30 on any given tumor. Are you familiar with their work? Rick Stanton: No, that’s beautiful. Dr.

John Laird: What they do that’s particularly relevant to this particular slide is assess CD8 cells, which are the ones that are going to be most helpful, from FOXP3 cells that put on the brakes. Anything that is 2/1 or over (CD8 to FOXP3) is considered good. Then they will look at CD163s, which are macrophages, and are also key.

Macrophages can be in an M1 stage or an M2 stage, and they transform back and forth. If they are in the M1 stage, that is very positive; if they are in the M2 stage, then that is a brake on the system. We can run the samples and get results, but they are not a high volume shop. It can take six weeks or more to get results back, but they’re very helpful.

This look at the microenvironment is something my mentor Mark Breniker had them set up a few years ago. You also get a protein fingerprint to give you a sense of which of these genetic changes are driving the tumor. No oncologists are going to make any treatment decisions based on this, but looking at the microenvironment terrain can often help in the off label environment.

Rick Stanton: I feel like going 20 deep in the IHC. Are these different slices of tissue, or are you able to stain and wash? Dr. John Laird: They end up with 20 slides. They need a block. Offline I can help get you set up. Rick Stanton: Are you acquainted with Akoya and NanoString’s spatial efforts? Dr. John Laird: I’m not.

“Tests and Treatments for Rick Stanton” [#3] Rick Stanton: You’re going to love them. It’s immunofluorescence, like an IHC. You’re able to do it on one slice of tissue. Immunofluorescence allows stain and wash. You are tagging the fluorescent molecule some color, typically red, green, or blue, to an antibody. You can go in three at a time with the three colors.

You could pick CD3, CD4, CD8 and iteratively build up to their high dimensional, up to 100 plex. I know they’re operating at 35. This is both Akoya and Enable. It’s like what you said, except it’s on one slice. NanoString enables even deeper querying. In the slide on the lower left, you could query boundary areas. Dr.