4 ms·

Based from another study: >> Patients with high ENPP1 levels had low response to pembrolizumab and high chance of metastases. Those with low ENPP1 levels had a

Based from another study: >> Patients with high ENPP1 levels had low response to pembrolizumab and high chance of metastases. Those with low ENPP1 levels had a high response to pembrolizumab and no metastases. ENPP1 predicted both response to immunotherapy and likelihood of relapse. Keytruda/PD-1 blocker: https://en.wikipedia.org/wiki/Pembrolizumab https://en.wikipedia.org/wiki/Pembrolizumab ENPP1 blockers already exist: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e14550 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e1...

superb_dev 3y ago
From the article: > This means that clinicians can use ENPP1 levels to better determine appropriate treatment for breast cancer patients. It also means that drugs that destroy the ENPP1 dam could make existing therapies more effective – and several ENPP1 inhibitors are already in clinical development.
jseliger 3y ago
At least one ENPP1 blocker appears to be in clinical trials already: https://clinicaltrials.gov/study/NCT05270213?term=RBS2418&rank=2 https://clinicaltrials.gov/study/NCT05270213?term=RBS2418&ra.... It lists "advanced cancers" as being eligible. I'm most interested in head and neck cancers, and pembrolizumab (Keytruda) is only effective in 20 - 30% of patients; see e.g. https://ascopubs.org/doi/full/10.1200/JCO.21.02198 https://ascopubs.org/doi/full/10.1200/JCO.21.02198: "In the phase Ib KEYNOTE-012 study of pembrolizumab monotherapy in R/M HNSCC (N = 192), objective response rate (ORR) was higher in patients with PD-L1 CPS ≥ 1 than CPS < 1 (21% v 6%; one-sided P = .023)." A lot of oncologists I've talked to also think PD-L1 expression is overrated as a marker of pembro effectiveness; obviously there's something going on, with higher PD-L1 expression being net better in terms of pembro utility overall, but the data are noisy and lots of exceptions abound. I'm also not sure how reliable PD-L1 expression tests are. My tumor was tested once by a well-known-in-the-field company called CARIS, and it showed a 20% Combined Positive Score (CPS). Another test done by the Mayo Clinic showed a 5% score. Who's right? Who knows. No one I've talked to. The attitude seems to be that no one is convinced the PD-L1 tests are highly accurate, and that once the CPS is above 1%, pembro's effectiveness is a crapshoot anyway. I got five doses of pembro and failed it, utterly.
- mahkeiro 3y ago
  This is the latest press release linked to the trial you have mentioned and their presentation at ESMO: https://www.riboscience.com/esmo-2023 https://www.riboscience.com/esmo-2023

superb_dev 3y ago

From the article: > This means that clinicians can use ENPP1 levels to better determine appropriate treatment for breast cancer patients. It also means that drugs that destroy the ENPP1 dam could make existing therapies more effective – and several ENPP1 inhibitors are already in clinical development.

jseliger 3y ago

At least one ENPP1 blocker appears to be in clinical trials already: https://clinicaltrials.gov/study/NCT05270213?term=RBS2418&rank=2 https://clinicaltrials.gov/study/NCT05270213?term=RBS2418&ra.... It lists "advanced cancers" as being eligible. I'm most interested in head and neck cancers, and pembrolizumab (Keytruda) is only effective in 20 - 30% of patients; see e.g. https://ascopubs.org/doi/full/10.1200/JCO.21.02198 https://ascopubs.org/doi/full/10.1200/JCO.21.02198: "In the phase Ib KEYNOTE-012 study of pembrolizumab monotherapy in R/M HNSCC (N = 192), objective response rate (ORR) was higher in patients with PD-L1 CPS ≥ 1 than CPS < 1 (21% v 6%; one-sided P = .023)." A lot of oncologists I've talked to also think PD-L1 expression is overrated as a marker of pembro effectiveness; obviously there's something going on, with higher PD-L1 expression being net better in terms of pembro utility overall, but the data are noisy and lots of exceptions abound. I'm also not sure how reliable PD-L1 expression tests are. My tumor was tested once by a well-known-in-the-field company called CARIS, and it showed a 20% Combined Positive Score (CPS). Another test done by the Mayo Clinic showed a 5% score. Who's right? Who knows. No one I've talked to. The attitude seems to be that no one is convinced the PD-L1 tests are highly accurate, and that once the CPS is above 1%, pembro's effectiveness is a crapshoot anyway. I got five doses of pembro and failed it, utterly.

mahkeiro 3y ago
This is the latest press release linked to the trial you have mentioned and their presentation at ESMO: https://www.riboscience.com/esmo-2023 https://www.riboscience.com/esmo-2023