18 ms·

Universal cancer vaccine trial shows significant improvement in overall survival

235 points by espenwa 3y ago

jseliger 3y ago
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 headline's current phrasing. It's like how people are horrified by "you have a 20% chance of dying" but somewhat reassured by "you have an 80% chance of living." I'm dying from squamous cell carcinoma and am more excited about the Moderna approach with personalized cancer vaccines, like mRNA-4157. Early data for what I have is promising: https://www.fiercebiotech.com/biotech/moderna-s-keytruda-combo-misses-colorectal-cancer-as-it-shows-promise-head-and-neck https://www.fiercebiotech.com/biotech/moderna-s-keytruda-com...: "The combination treatment shrank tumors in five patients with head and neck cancer (50%), eliminating the tumors in two of those patients, Moderna said in a statement. Another four patients in that group had stable disease, meaning their tumors had stopped growing." Recurrent/metastatic head and neck squamous cell carcinoma is almost always fatal: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155962/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155962/, unless the person responds to pembrolizumab/Keytruda (which I do not; about 20 - 30% of patients appear to respond, based on KEYNOTE-048: https://ascopubs.org/doi/full/10.1200/JCO.21.02508 https://ascopubs.org/doi/full/10.1200/JCO.21.02508). Unfortunately, Moderna won't make mRNA-4157 available under compassionate use or through any other means. :( Moderna, however, is in a Phase III study of mRNA-4157 in melanoma: https://www.onclive.com/view/adjuvant-mrna-4157-plus-pembrolizumab-improves-rfs-in-resected-high-risk-melanoma https://www.onclive.com/view/adjuvant-mrna-4157-plus-pembrol.... Given the miraculous early data for R/M HNSCC, one hopes they'll launch new trials. Nivolumab is a PD-1 inhibitor, like pembrolizumab/Keytruda, but I don't know anything more about it.
- criley2 3y ago
  "Phase II studies are ongoing in patients with malignant melanoma, head and neck cancer, ovarian cancer, and non-small cell lung cancer."
  - jseliger 3y ago
    Thank you! I missed that sentence. Embarrassing. Will be interested to see how it performs.
- huytersd 3y ago
  Weren’t you able to get into the study at UCSD? How is that going? Are you allowed to talk about it?
  - jseliger 3y ago
    I was! I've now been infused twice with 1100mg of petosemtamab / MCLA-158 (https://beta.clinicaltrials.gov/study/NCT03526835 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/ 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.
berbec 3y ago
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 https://i.postimg.cc/L4G0FdWf/cancer-study.jpg
- criley2 3y ago
  These are Phase II trials.
  - ramraj07 3y ago
    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.
- extraduder_ire 3y ago
  Is this image from something with stats? The numbers seem kind of round. Not that specific stats would help me that much.
- Neil44 3y ago
  It's part of the huge, finger in the air balancing act of developing drugs. How much money do you put into early phase 1 and before stuff that may or may not make it. And what's the market if it does make it. Because the ones that do make it have to cover the cost of all the ones that don't, who's learning it took to get to this point.
m3kw9 3y ago
27% doesn’t seem all that significant considering a vaccine
- brokensegue 3y ago
  >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
  - somenameforme 3y ago
    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.
    - brokensegue 3y ago
      The flu vaccine reduces severity and likelihood of catching it as well (which can serve to protect vulnerable populations). Your own personal chance of death is not all that matters. Getting it yearly may also reduce the risk of other related conditions e.g. https://www.uth.edu/news/story/uthealth-houston-study-flu-vaccination-linked-to-40-reduced-risk-of-alzheimers-disease https://www.uth.edu/news/story/uthealth-houston-study-flu-va... It's nearly risk free and it's definitely worth it even if all it did was decrease the severity of flu if you catch it (and it does more than that).
erickf1 3y ago
Sounds like another money maker for the pharmaceutical industry that does nothing for the patient.
cpncrunch 3y ago
“the study did not meet the primary endpoint”
andrewstuart 3y ago
2035: "How are you feeling?" "Oh, a touch of cancer last week but I popped a couple of pills and all good now".
anovikov 3y ago
This is officially the king of all clickbait
- cpncrunch 3y ago
  Indeed. It failed its primary endpoint, and yet someone posted this press release.
jorgtron 3y ago
Note that this is for a very hard cancer to treat, and no one was expecting the great results seen here. Upcoming studies will focus on other cancer types where we expect results to be even better. Disclaimer: I'm an investor in Ultimovacs and run a community for Ultimovacs investors at tekinvestor.no (in Norwegian, but google translate can help :)) "Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical development program across various cancer indications with different biologies and disease stages, in combination with different checkpoint inhibitors. The topline data from NIPU are the first results among the five randomized trials in the UV1 Phase II clinical program. In addition to malignant mesothelioma, Phase II studies are ongoing in patients with malignant melanoma, head and neck cancer, ovarian cancer, and non-small cell lung cancer. The topline data from the malignant melanoma and head and neck cancer trials are expected during the first and second half of 2024. UV1 is a patented, proprietary technology owned by Ultimovacs."
jl2718 3y ago
“UV1 is a therapeutic cancer vaccine used to generate an immune response against the enzyme human telomerase (hTERT). The enzyme is essential for the ability of cancer cells to proliferate. Telomerase is present in 85-90% of all cancers, across the stages of the disease.” It’s a protein epitope vaccine against a normal human protein. Not stated here, but it may also target normal stem cells needed for repair and renewal processes. This risk may be reduced by the cessation of checkpoint blockades, but, the immune system can’t forget a target, and autoimmunity is an unsolved problem. HLA binding is also not perfectly specific, and any immune response is likely to generate more immunity from the target cell. This universal targeting of normal peptides may be an acceptable last-line defense, but I would be more comfortable targeting a somatic mutation with some significant differentiation from anything in the human exome.
- olifante 3y ago
  > the immune system can’t forget a target This recent study has developed an “inverse vaccine” for multiple sclerosis that apparently can make the immune system forget stuff: https://news.ycombinator.com/item?id=37528816 https://news.ycombinator.com/item?id=37528816
- justinclift 3y ago
  > the immune system can’t forget a target Doesn't catching measles reset the immune system's "memory"?
  - jl2718 3y ago
    I don’t know much about this, but I’m not sure “reset” is the right term here. It seems more like “overwhelm” than “reset” to what a newborn might have. Measles can cause autoimmunity, and I’m not sure it’s been shown to abate it.
    - justinclift 3y ago
      k. I was going by stuff like this: https://www.bbc.com/future/article/20211112-the-people-with-immune-amnesia https://www.bbc.com/future/article/20211112-the-people-with-...
mkoryak 3y ago
Why are some metrics using an 80% confidence interval while others use 95%?

235 points by espenwa 3y ago

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 headline's current phrasing. It's like how people are horrified by "you have a 20% chance of dying" but somewhat reassured by "you have an 80% chance of living." I'm dying from squamous cell carcinoma and am more excited about the Moderna approach with personalized cancer vaccines, like mRNA-4157. Early data for what I have is promising: https://www.fiercebiotech.com/biotech/moderna-s-keytruda-combo-misses-colorectal-cancer-as-it-shows-promise-head-and-neck https://www.fiercebiotech.com/biotech/moderna-s-keytruda-com...: "The combination treatment shrank tumors in five patients with head and neck cancer (50%), eliminating the tumors in two of those patients, Moderna said in a statement. Another four patients in that group had stable disease, meaning their tumors had stopped growing." Recurrent/metastatic head and neck squamous cell carcinoma is almost always fatal: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155962/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155962/, unless the person responds to pembrolizumab/Keytruda (which I do not; about 20 - 30% of patients appear to respond, based on KEYNOTE-048: https://ascopubs.org/doi/full/10.1200/JCO.21.02508 https://ascopubs.org/doi/full/10.1200/JCO.21.02508). Unfortunately, Moderna won't make mRNA-4157 available under compassionate use or through any other means. :( Moderna, however, is in a Phase III study of mRNA-4157 in melanoma: https://www.onclive.com/view/adjuvant-mrna-4157-plus-pembrolizumab-improves-rfs-in-resected-high-risk-melanoma https://www.onclive.com/view/adjuvant-mrna-4157-plus-pembrol.... Given the miraculous early data for R/M HNSCC, one hopes they'll launch new trials. Nivolumab is a PD-1 inhibitor, like pembrolizumab/Keytruda, but I don't know anything more about it.

criley2 3y ago
"Phase II studies are ongoing in patients with malignant melanoma, head and neck cancer, ovarian cancer, and non-small cell lung cancer."
- jseliger 3y ago
  Thank you! I missed that sentence. Embarrassing. Will be interested to see how it performs.
huytersd 3y ago
Weren’t you able to get into the study at UCSD? How is that going? Are you allowed to talk about it?
- jseliger 3y ago
  I was! I've now been infused twice with 1100mg of petosemtamab / MCLA-158 (https://beta.clinicaltrials.gov/study/NCT03526835 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/ 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.

berbec 3y ago

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 https://i.postimg.cc/L4G0FdWf/cancer-study.jpg

criley2 3y ago
These are Phase II trials.
- ramraj07 3y ago
  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.
extraduder_ire 3y ago
Is this image from something with stats? The numbers seem kind of round. Not that specific stats would help me that much.
Neil44 3y ago
It's part of the huge, finger in the air balancing act of developing drugs. How much money do you put into early phase 1 and before stuff that may or may not make it. And what's the market if it does make it. Because the ones that do make it have to cover the cost of all the ones that don't, who's learning it took to get to this point.

m3kw9 3y ago

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

brokensegue 3y ago
>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
- somenameforme 3y ago
  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.
  - brokensegue 3y ago
    The flu vaccine reduces severity and likelihood of catching it as well (which can serve to protect vulnerable populations). Your own personal chance of death is not all that matters. Getting it yearly may also reduce the risk of other related conditions e.g. https://www.uth.edu/news/story/uthealth-houston-study-flu-vaccination-linked-to-40-reduced-risk-of-alzheimers-disease https://www.uth.edu/news/story/uthealth-houston-study-flu-va... It's nearly risk free and it's definitely worth it even if all it did was decrease the severity of flu if you catch it (and it does more than that).

erickf1 3y ago

Sounds like another money maker for the pharmaceutical industry that does nothing for the patient.

cpncrunch 3y ago

“the study did not meet the primary endpoint”

andrewstuart 3y ago

2035: "How are you feeling?" "Oh, a touch of cancer last week but I popped a couple of pills and all good now".

anovikov 3y ago

This is officially the king of all clickbait

cpncrunch 3y ago
Indeed. It failed its primary endpoint, and yet someone posted this press release.

jorgtron 3y ago

Note that this is for a very hard cancer to treat, and no one was expecting the great results seen here. Upcoming studies will focus on other cancer types where we expect results to be even better. Disclaimer: I'm an investor in Ultimovacs and run a community for Ultimovacs investors at tekinvestor.no (in Norwegian, but google translate can help :)) "Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical development program across various cancer indications with different biologies and disease stages, in combination with different checkpoint inhibitors. The topline data from NIPU are the first results among the five randomized trials in the UV1 Phase II clinical program. In addition to malignant mesothelioma, Phase II studies are ongoing in patients with malignant melanoma, head and neck cancer, ovarian cancer, and non-small cell lung cancer. The topline data from the malignant melanoma and head and neck cancer trials are expected during the first and second half of 2024. UV1 is a patented, proprietary technology owned by Ultimovacs."

jl2718 3y ago

“UV1 is a therapeutic cancer vaccine used to generate an immune response against the enzyme human telomerase (hTERT). The enzyme is essential for the ability of cancer cells to proliferate. Telomerase is present in 85-90% of all cancers, across the stages of the disease.” It’s a protein epitope vaccine against a normal human protein. Not stated here, but it may also target normal stem cells needed for repair and renewal processes. This risk may be reduced by the cessation of checkpoint blockades, but, the immune system can’t forget a target, and autoimmunity is an unsolved problem. HLA binding is also not perfectly specific, and any immune response is likely to generate more immunity from the target cell. This universal targeting of normal peptides may be an acceptable last-line defense, but I would be more comfortable targeting a somatic mutation with some significant differentiation from anything in the human exome.

olifante 3y ago
> the immune system can’t forget a target This recent study has developed an “inverse vaccine” for multiple sclerosis that apparently can make the immune system forget stuff: https://news.ycombinator.com/item?id=37528816 https://news.ycombinator.com/item?id=37528816
justinclift 3y ago
> the immune system can’t forget a target Doesn't catching measles reset the immune system's "memory"?
- jl2718 3y ago
  I don’t know much about this, but I’m not sure “reset” is the right term here. It seems more like “overwhelm” than “reset” to what a newborn might have. Measles can cause autoimmunity, and I’m not sure it’s been shown to abate it.
  - justinclift 3y ago
    k. I was going by stuff like this: https://www.bbc.com/future/article/20211112-the-people-with-immune-amnesia https://www.bbc.com/future/article/20211112-the-people-with-...

mkoryak 3y ago

Why are some metrics using an 80% confidence interval while others use 95%?