Pluvicto for Prostate Cancer: Patient Experiences, Side Effects, & Efficacy

•Patient Profile (seven patients)

•These are all advanced prostate cancer patients who have seen, on average, four systemic therapies.

•All but one has been on first and second-line hormone therapy.

•All but one has been on chemotherapy.

•All patients have bone metastases, with the exception of one who has lymph node metastases only.

•Screening

•Pylarify-only: Plylarify (PSMA-PET, a scan that lights up cells with prostate- specific membrane antigen) SUVs (Standard Uptake Values) are the primary means to determine Pluvicto candidacy. SUVs ranged from 7-24.

•Pylarify + Axumin PET: One patient treated at MD Anderson used a combination of Pylarify and Axumin PET to assess the concordance of PSMA-avid disease.

•Genomics/RNAseq: No Pluvicto patient used RNA sequencing or other genomic insights to assess candidacy. PSMA gene expression relative to other prostate cancer patients could help determine patient fit with Pluvicto treatment. However, one Prostate Cancer Lab patient has used his PSMA RNA gene expression relative to a 1,000 prostate cancer cohort to deprioritize Pluvicto as a treatment option.

•Treatment Response

•Durability: With an average response duration of 6.5 months, patients found the treatment fell short of durability expectations.

•PSA response: Five of the seven patients saw a PSA decline through the third round. However, those patients saw PSA increases after the fourth round and discontinued. Two patients continued through the prescribed sixth round. ■Note: Two patients experienced immediate PSA increases.

•Side Effects

•Most common: Fatigue was the most common side effect. One patient felt that exercise was important to minimize fatigue.

•Most serious: ■One patient lost his salivary glands and his appetite. He was very sick from treatment. ■One patient experienced myelosuppression, but it is not clear that Pluvicto was the driver.

•Follow-up to Pluvicto Treatment

•Three patients switched from Pluvicto to a chemotherapy

•Two patients moved to Bipolar Androgen Therapy (BAT)

•One patient pursued spot radiation Patient Data Table Pluvicto Patient Interviews 20230503 (Please click on the link above or see the table at the end of the transcript.) Additional Context The manufacturer of Pluvicto is Novartis. Pluvicto is a key launch for Novartis and part of the company’s broader interest in radiotherapy. Banking on the potential to move into earlier prostate cancer treatment, Novartis put Pluvicto’s peak sales projection above $2 billion. Novartis aims to have a 250,000-dose annual capacity for Pluvicto in 2024. From FiercePharma, "250,000 doses would translate into $8 billion of revenue at Pluvicto’s current U.S. price. Doctors’ experience thus far shows that Pluvicto has yet to reach its full potential in post-taxane mCRPC. In the clinical trial used for its approval, the drug showed it could reduce the risk of death by 38% when added to best standard-of-care in PSMA-positive mCRPC patients who had tried an androgen receptor inhibitor and at least one taxane-based chemotherapy regimen. And Novartis just reported positive pre-taxane mCRPC data from the phase 3 PSMAfore trial. If approved in that setting, Pluvicto’s eligible patient pool could expand from 27,000 to 42,000 patients... The company is accumulating more data at the FDA’s request, with a plan to file for an approval in the second half of this year. In addition, Novartis is testing Pluvicto in metastatic hormone-sensitive prostate cancer in the PSMAddition trial, which has a primary completion date in 2024." The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. 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. Meeting Notes The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. 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. SUMMARY KEYWORDS docetaxel, psa, treatment, patients, russ, side effects, scan, neuroendocrine, prior, bone, infusions, suv, androgens, chemotherapy, salivary glands, bat, expression, started, fatigue, chemo SPEAKERS Robert Gurmankin, Brian McCloskey, Brad Power, Russ Hollyer, Chad Magnussen, Ken Anderson, Mike Yancey, Amit Gattani, Emma Shtivelman, Rick Stanton, Mark Lanctot Brian McCloskey The reason why we're having this discussion today is that a couple of weeks ago, there was some discussion around Pluvicto. It centered around its effectiveness and the side effects that you had. I know personally, as well as talking to many of you, that depending upon where you are in your journey, it seems to be the go-to drug treatment. What we think would be helpful is to collect any information that we have from those who have gone through Pluvicto, to understand its effectiveness and its side effects. We can use that obviously to educate other patients that come into the Prostate Cancer Lab. To that end, I put together a few unscientific questions. I'm going to read them just so that you all have a sense of what they are, and I'm going to go across the panel of patients who I know have been on Pluvicto. I'll prompt you through the questions, but let me give you a summary.

•It would be nice to know what your prior treatment is.

•Fo

•For many of you, I know when you were diagnosed. If you are new, I may not know your diagnosis date and that would be helpful because that tells me where you are on your journey.

•What kind of screening did you have? Did they just look at Standard Uptake Values, SUVs? Did they look at PSMA expression, or were there other characteristics of your cancer that came to light?

•If you did start it, when did you start it?

•What was your starting PSA?

•How many rounds did you go through? Not everyone goes through all six rounds.

•What was the end date?

•What was your PSA Nadir through that process?

•Did you have any side effects?

•I'd like a very unscientific rating on the drug, such as, 1 being completely dissatisfied and 5 being completely satisfied.

•Would you recommend it to a friend?

•What's your post Pluvicto treatment, and any general commentary? That's quite a few questions, so we should probably try to cap it at roughly seven minutes or so per patient. I will start off with Amit, if you can give me your perception of Pluvicto starting off with what your prior treatment was. Just your immediate prior treatment, not your entire lineage but just the one prior to it. Amit Gattani 04:27 My immediately prior treatment was chemotherapy. I was on chemotherapy before that and I was kind of refractory to that. We tried docetaxel again while waiting for Pluvicto to become available. I started on Pluvicto around August of 2022. I got three doses every six weeks. My PSA in that phase actually increased from around 284 to the 350 range over that period of time. My last dose was in December of 2022. The side effects were part of the reason we had to stop at three doses due to myelosuppression. All three cell lines were starting to do poorly at that time. Prior to that I had gone through VMAT radiation. It's hard to say that it was only Pluvicto because VMAT radiation also reduced the bone marrow capacity. Was it Pluvicto that led me down myelosuppression? It wasn't a standalone variable, and we should keep that in mind. But the reason I had to stop after three doses was that my cell lines were too low and not safe to give me Pluvicto anymore. And in that time period, we did not see any meaningful, positive result from Pluvicto either from a PSA perspective. I have had these PSMA scans in the past and my disease seemed pretty highly PSMA avid. SUV values were pretty high too. I was very eager to get this treatment, actually, because it's a targeted treatment compared to everything else. We were all very hopeful that this was a better targeted treatment approach. So PSMA scans with high SUVs indicated this was a good approach to try. With respect to the results, I've seen data that PSA is not the best indicator being on Pluvicto. I don't have a great answer that Pluvicto helped me or not, but I'll share some information. The PSMA scan before that had a high concentration PSMA indicated a high tumor volume. PSMA post Pluvicto did show some diffusion of those areas. So presumably certain tumors did benefit from having Pluvicto. Now again, that's very qualitative information. Radiology hasn't given me any measured information. I've been on multiple things at the same time so it's hard to isolate things. But we did see some dispersion happen. Some of the spots were not as dark. Now one other side note is that during this time, the disease moved from being just in the bone to bone marrow. Again, probably nothing to do with Pluvicto, but it happened during the same period of time that my disease moved from being just in the bones and bone mets to actually getting into the bone marrow. Brian McCloskey 08:50 Super helpful. So I think you've covered everything except your post-Pluvicto treatment. Can you tell me what that was? Amit Gattani 09:01 My post-Pluvicto treatment is I'm on chemo again now. A carboplatin plus Cabazitaxel. Rick Stanton 09:13 Was that directed by any molecular evidence? Amit Gattani 09:24 Rick, what was directed by molecular evidence? Rick Stanton 09:27 Do you have any bone biopsies that might provide molecular direction? I'm looking for mProbe. Amit Gattani 09:47 The chemo is driven by the fact that I now have neurondocrine differentiation. The chemo is all driven by my current state of neuroendocrine plus adenocarcinoma. With all the myelosuppression and disease being in the bone marrow, my body’s ability to take treatments is very marginal. Rick Stanton 10:14 Just curious how neuroendocrine was determined. Amit Gattani 10:19 Through a prostate tissue biopsy. At the end of February, the prostate tissue biopsy showed that I have neuroendocrine differentiation, bone disease, and in the bone marrow...many, many things changed. Rick Stanton 10:38 I'm heading the same way. What type of analysis from the biopsy determined neuroendocrine? Amit Gattani 10:45 It was a basic pathology at the hospital that determined neuroendocrine. It has been validated multiple times. I had a TURP surgery at the end of February, so they were able to get some new prostate tissue because of the procedure. From that, the basic pathology and biopsy revealed a neuroendocrine component to it. Brian McCloskey 11:23 Amit, thank you. I'm going to stick to the rigor here. Maybe these questions are kind of marketing only, but I'm going to go with it and see how this turns out. If you were to rate this drug, on a scale of one to five, from completely dissatisfied as a one to completely satisfied as a five, what would you rate this drug? Amit Gattani 11:51 I would put it in the middle. I mean, again, I believe in targeted treatments. And I think again, everybody may respond differently. So I would not dissuade anybody from considering it seriously. Results and mileage will vary. Brian McCloskey 12:09 Good point. Thank you. I'm going to move on to Chad. Chad, can you tell us about your experience? The first question is what was your prior treatment, just your immediate prior treatment? Chad Magnussen 12:30 Obviously ADT, and then I had docetaxel chemotherapy followed by a carboplatin chemotherapy. Brian McCloskey 12:40 What was the drug that immediately preceded Pluvicto? Chad Magnussen 12:47 Carboplatinum. Brian McCloskey 12:50 Okay. Got it. And did you do that with cabazitaxel or just straight carbo? Chad Magnussen 12:56 With docetaxel. Brian McCloskey 13:04 From a screening perspective, what did you do? PSMA-PET? Did they look at SUVs? Did you do anything else to determine whether or not you are a good fit? Chad Magnussen 13:13 Yeah, so we did PSMA-PET and looked at the SUVs. There were a few that were similar and were high. My score was a two. Mayo Clinic rates three as a high, two is a medium, one is a low and zero is a No. So basically I was at two, so I could qualify. There were five tumors that they were monitoring. I started this in April. I was patient number 90 at Mayo Clinic, right after it was approved. I just finished round six. When I started, I had a PSA of 0.81. I had a flare that went to 1.4. It dropped pretty rapidly after that and went down to 0.77. But then now, for this last one, I am now 0.93. So the roller coaster of PSA. SUV values on the five tumors - there were two tumors that had a very low SUV of like 1.5 in a week after treatment. I did just a spec, low quality scan, and it appeared those two are gone and they're not monitored anymore. For the three larger ones, the SUV values went from in the elevens to the sevens. If two are gone, obviously, that's a good thing. And then there was some effect on the SUV value. I have seven choline scans scheduled the first week in June to really tell what this has done. So as of right now, I'm not sure what's going on. I was very sick. I would put this on par with carboplatin. I was very, very sick. Loss of appetite for a good 10 days. But the biggest thing for me is my salivary glands are completely gone. I mean, I have to drink just to talk. That's been a tough one for me. I wake up in the night and my tongue is stuck in my teeth. And it's just been a really tough go for me. Brian McCloskey 16:22 Did they tell you that you were for some reason at high risk for that. I mean, it's a risk for all Pluvicto patients, but yours seems to be more severe. Chad Magnussen 16:37 About the fourth one, when I started talking about it, they started mentioning how it shows up on the low quality scan and you could see the jaw light up so obviously it's going to that. Brian McCloskey 17:00 Any other side effects? Chad Magnussen 17:01 So far my blood numbers stayed the same. They were all pretty low coming off carboplatin, but they all stayed the same. For example my hemoglobins, I started at 12.9 and now it's 12.1. It just all stayed the same, so it didn't affect my blood numbers too badly. I was working really hard to keep them up with some supplements and juicing and all that. I think that helped. But as far as that goes, just the immediate sickness for about 10 days afterwards was really rough for me. Brian McCloskey 17:38 Do you know what you're contemplating for your next treatment? Chad Magnussen 17:50 Immediately we're going to do some spot radiation. I was worried that I had too many spots for spot radiation. And now if these two are gone, I think I have three to spot radiate so I think that's next for me followed by Abiraterone and progesterone. Brian McCloskey 18:09 Got it. On a scale of one to five, how would you rate the drug? One is completely dissatisfied. Five is satisfied, or completely satisfied. Chad Magnussen 18:20 I was pretty excited for this as I was obviously one of the first ones on it. I don't think it's paid off. It wasn't what I was hoping for, but obviously the scan I have coming in June is really going to tell the story. Right now I'm in the middle. Brian McCloskey 18:48 Would you recommend it to a friend? It sounds kind of corny, but we're just gonna go with it for now. Chad Magnussen 18:55 I would do three of them and get a scan in the middle and really monitor what's going on. I think