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Universal cancer vaccine trial shows significant improvement in overall survival

ultimovacs.com

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Re: Universal cancer vaccine trial shows significant improvement in overall survival

#12
post #2

This is obviously good but note that it appears to be covering mesothelioma only, and "The median [overall survival] OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab and nivolumab alone." Another headline could be: "Cancer vaccine helps some mesothelioma patients live an extra 4.3 months," which is less exciting than the…

> Unfortunately, Moderna won't make mRNA-4157 available under compassionate use

Sorry to hear. Try contacting Immunocore in Oxford, they have a TCR therapy that targets many tumors, including squamous ones, and they are recruiting or should make it available under compassionate use. Other companies worth looking into are Adaptimmune Therapeutics, also in Oxford, and Evaxion in Copenhagen. They are all going the semi-personalized route. So will look into your tumor type, MHC class I, etc.

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#13
post #10

27% doesn’t seem all that significant considering a vaccine

>A 2021 study showed that among adults hospitalized with flu, vaccinated patients had a 26% lower risk of intensive care unit (ICU) admission and a 31% lower risk of death from flu compared with those who were unvaccinated.

Yet you should still be getting the flu vaccine

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#14
post #6
post #2

This is obviously good but note that it appears to be covering mesothelioma only, and "The median [overall survival] OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab and nivolumab alone." Another headline could be: "Cancer vaccine helps some mesothelioma patients live an extra 4.3 months," which is less exciting than the…

Weren’t you able to get into the study at UCSD? How is that going? Are you allowed to talk about it?

I was! I've now been infused twice with 1100mg of petosemtamab / MCLA-158 (https://beta.clinicaltrials.gov/study/NCT03526835), on Sept. 27 and then Oct. 12. The next is Oct. 25. For the first week I had no apparent reactions, and then a rash erupted on my face, chest, and back. That's pretty normal for EGFR drugs, and the rash was (and is) itchy and annoying but not unbearable. To treat it, I inject an antibiotic called doxycycline (which is used against acne bacteria) into my peg tube and use a a topical steroid. At the bottom of this post: https://jakeseliger.com/2023/10/16/how-do-you-say-goodbye/ there's a photo showing some of what's happening to my face.

So, overall it's going pretty well, and I feel physically better than I did on chemo and Keytruda—a low bar, but I'll take whatever improvements I can get. The next CT scans are scheduled for Nov. 21, but unless I'm responding to petosemtamab in a pretty major way, they'll probably be ambiguous. The median time to respond is 1.8 months, so it'd be surprising to see big changes between the Sept. 5 CT baseline CT scans and the Nov. 21 scans. Two tumors are physically protruding from my neck, which is disconcerting, but they aren't painful.

The FDA apparently wants to see how the 1100mg and 1500mg petosemtamab doses differ, and I got randomized to the lower dose. That isn't necessarily bad: more of a drug can be deleterious relative to right dose.

I wasn't NDA'ed, so I'm assuming I can talk about what's going on. I'm a bit surprised by the lack of an NDA; I've signed NDAs for three-person startups who want grant writing services for a Dept. of Energy Small Business Innovation and Research (SBIR) proposal, but nothing WRT this.

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#15
post #4
post #2

This is obviously good but note that it appears to be covering mesothelioma only, and "The median [overall survival] OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab and nivolumab alone." Another headline could be: "Cancer vaccine helps some mesothelioma patients live an extra 4.3 months," which is less exciting than the…

"Phase II studies are ongoing in patients with malignant melanoma, head and neck cancer, ovarian cancer, and non-small cell lung cancer."

Thank you! I missed that sentence. Embarrassing. Will be interested to see how it performs.

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#16
post #8
post #2

This is obviously good but note that it appears to be covering mesothelioma only, and "The median [overall survival] OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab and nivolumab alone." Another headline could be: "Cancer vaccine helps some mesothelioma patients live an extra 4.3 months," which is less exciting than the…

Do you have an opinion on https://www.science.org/content/blog-post/new-mode-cancer-tr... ?

Nope. Nothing other than "I hope it works!" Interestingly, AOH1996 is supposed to be given at Honor Health Research Institute: https://beta.clinicaltrials.gov/study/NCT05227326, which is down the street from me, but the trial isn't listed as recruiting yet. Not sure why: if I weren't in the trial I'm in (https://news.ycombinator.com/item?id=37924671), AOH1996 would likely be on the list. It's a first-in-human trial with only 8 participants, and most drugs, even super promising-seeming ones, don't make it even to phase 2.

But https://www.clinicaltrials.gov/study/NCT04787042 is also a promising phase 1 trial for an interleukin-18 attack, and it's also at Honor Health.

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#17
post #8
post #2

This is obviously good but note that it appears to be covering mesothelioma only, and "The median [overall survival] OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab and nivolumab alone." Another headline could be: "Cancer vaccine helps some mesothelioma patients live an extra 4.3 months," which is less exciting than the…

Do you have an opinion on https://www.science.org/content/blog-post/new-mode-cancer-tr... ?

Not who you asked but that’s a promising molecule. Unfortunately until we see phase 1/2 results we can’t be sure if it ends up actually being effective. It’s sad that we can’t predict efficacy any better without injecting actual people with the drug but that’s reality. Cancer is too complex to model any other way in a complete fashion. If a drug is blockbuster effective you’d notice in phase 1 itself, as was the case for ibrutinib. Fingers crossed.

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#18
post #5
post #3

I have a friend doing her PhD in cancer research. She tells me to take every Phase I trial with a huge grain of salt, because they rarely make it to market. [1] 1: https://i.postimg.cc/L4G0FdWf/cancer-study.jpg

These are Phase II trials.

There’s a lot of approved cancer treatment protocols that increase median survival by a mere few weeks. This drug also seems to be heading that way.

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#19
post #6

Earlier quoted context omitted.

Weren’t you able to get into the study at UCSD? How is that going? Are you allowed to talk about it?

I was! I've now been infused twice with 1100mg of petosemtamab / MCLA-158 ( https://beta.clinicaltrials.gov/study/NCT03526835 ), on Sept. 27 and then Oct. 12. The next is Oct. 25. For the first week I had no apparent reactions, and then a rash erupted on my face, chest, and back. That's pretty normal for EGFR drugs, and the rash was (and is) itchy and annoying but not unbearable. To treat it, I inject an antibiotic c…

Thanks for the update and I hope this works out.

Re: Universal cancer vaccine trial shows significant improvement in overall survival

#20
post #10

27% doesn’t seem all that significant considering a vaccine

>A 2021 study showed that among adults hospitalized with flu, vaccinated patients had a 26% lower risk of intensive care unit (ICU) admission and a 31% lower risk of death from flu compared with those who were unvaccinated. Yet you should still be getting the flu vaccine

Numbers like that are highly misleading, because it's a conditional. If your chances of dying from something are 1 in 10 million, and a treatment changes that to 1 in a billion, then that treatment would mean you're 99% less likely to die of whatever. But the risk of death is so extremely low to begin with, that that 99% figure is largely just noise.

I mean noise in both the colloquial sense, as well as the statistical one. It's difficult to measure the effectiveness of treatments when what you're treating is so relatively harmless. An experimental study, outside of an absurd size, would show 0 deaths. So you only have observational studies left, which tend to be deeply flawed and highly susceptible to number juking.

In any case, if somebody dies from the flu they were likely quite elderly, or had severe preexisting conditions. And so it's this group of people that taking things like a flus hot can make the most sense. But if you take e.g. a younger to mid aged person of good health, his chance of dying from the flu are practically zero. If they want to get it, more power to them. But saying all people should get a flu shot, does not seem to make much sense.

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