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Senti, in the Car-t trial you are analyzing, when they say “all” tumors regressed (starting day 133), they were not talking about tumors 1, 2 or 3, I think. They believe those sites remained stable after 100% resection.
They are counting tumor stabilization to extend their 7.5 month “dramatic” response claim.
That makes this paragraph by them a bit disingenuous, because it lumps in stabilization with tumor response.
While I understand your conservative times, if, and that’s a big if, no RFI, then there is no rule saying the MHRA has to wait 70 days. Given they would not need to review a response to an RFI in that situation, the deliberation is much much shorter than it would otherwise be, which might mean a great deal shorter than 70 days.
That said, we do not know if there was no RFI.
Senti, another reflection about your analysis on the Car-T trial:
Because there are so many “tumors”, I’d think it would be worth having your own graphic timeline of when you believe “tumors” one through twelve appear in juxtaposition to surgery and treatments, along with when the reported complete response starts and ends on which “tumors.”
In your timeline, you should also include when the patient deceased.
The article’s masking technique is really atrocious, but it also somehow makes the reader feel like it is their own fault for being confused, and therefore no one speaks up. Until you figured out the false narrative.
If one could rank the deception level by tumor however, I’d say “tumors” four and five were their biggest timeline deceptions.
For what it’s worth, I think you are spot on correct.
Personally, I’m still not convinced that # 4,5,6,7 or 8 were all tumors. They could have been those weird transient nodules, which is sometimes a side effect of Car-t.
Anyway, now we know, if my memory is correct, that the patient did not live more than 18 months after he started treatment.
Because they did not take a new MRI until day 231, those new tumors 9,10, etc, would have been growing for months.
The author, the Journal and the peer review people need to withdraw the article and re-publish. Their timeline for partial/complete response, if any, is way too long. Instead, two months, tops.
Edit: SRD is 10.6% at risk at five years. For DCVax-l
MRD is 10.9% at risk at five years for DCVax-l
Long term survival is where the impact is expected to be highest with cancer vaccine therapy.
You’ll also notice it appears significant residual disease (where I logically assume most mesenchymal are) will surpass minimum residual disease by year six.
This would not be the case with SOC therapy. It would be the opposite, and by a much wider margin.
(And of course SOC SRD OS would be less than half that by that time, essentially zero)
Continued: And of course SOC OS would be less than half that by that time.
SRD is 10.9% at risk at five years. For DCVax-l
MRD is 10.6% at risk at five years for DCVax-l
Long term survival is where the impact is expected to be highest with cancer vaccine therapy.
You’ll also notice it appears significant residual disease (where I logically assume most mesenchymal are) will surpass minimum residual disease by year six.
This would not be the case with SOC therapy. It would be the opposite, and by a much wider margin.
#dcvax $nwbo #gbm
— Peter Davis (@peter_brit) March 31, 2024
As Vivek Subbiah, MD continues his important work promoting Tissue-Agnostic therapies in precision medicine, from a previous conference he attended at the SABCS in Dec 2023, some incredible highlights are quoted below:-
Tumor-agnostic therapies advance… https://t.co/HC1ZxuN5tv
Thank you. I will read more about it. One might conjecture the starting material for “SEC” analysis might vary from tumor lysate, blood, lymph and their immune constituents, and that changes over time, for instance, after targeting many antigens and what remaining and new cancer adaptations appear will be known on a real time basis.
Doesn’t matter who thought of it first.
My thought was/is one short course of tmz, maybe four weeks, (because otherwise tmz inhibits t-cells & other immune cells) when tumor has/had methylated mgmt, followed by a normal course of DCVax-l therapy, followed by DCVax-l maintainance boosters.
With unmethylated mgmt, maybe no TMZ, and receive DCVax-l therapy, followed by DCVax-l maintainance boosters.
Of course there are many more things they are hoping to incorporate with DCVax-l, like add poly-iclc, plx3397 and perhaps CI.
I think even Dr. Stupp has come around to not necessarily giving tmz to unmethylated patients.
JMHO.
There are other types of IP including biologic exclusivity which protects a biologic from biosimilars for ten years from the date it is approved. If you think that’s not enough, there is data exclusivity, which prevents other companies from using DCVax trial data to prove safety and efficacy. On top of that, DCVax-Direct has patents on method B+ out to 2036. Additionally, DCVax-l + checkpoint inhibitor is patented in several places, including Europe out to 2036.
Residual disease in the DCVax-l trial.
Remember, the easier tumors to resect are not the ones DCVax-l works best on. Instead, mesenchymal tumors are more infiltrative and tend to spread out in various directions. Mesenchymal tumors are probably why there are so many partial resections in the DCVax-l trial.
That’s in part confirmed, imho, by the NYAS DCVax slide deck, because, for overall survival at five years, DCVax-l proved statistically superior to the external control arm in treating patients with significant residual disease.
Equally important, but under appreciated, overall survival at five years for DCVax-l treating patients with significant residual disease, was equal to DCVax-l treating minimum residual disease patients. Both have essentially 13% five year survival, and both have almost 11% patients at risk — at five years.
This then logically disproves EX’s assertion that DCVax-l did not really beat the external significant residual control arm, because the treatment arm supposedly had better resections.
I’m under the weather this weekend, but my last three posts, aside from a real time math error, make an important point.
I’ll try to take some time, clean them up, and condense them altogether in one post. Later today or tomorrow.
Excuse me: Same point, but DCVax-l with significant residual disease (10.6% at risk) uncharacteristically (but logically) essentially tied DC-Vax-l with minimal residual disease (10.9% at risk) regarding five year survival.
That disproves Ex’s point.
Note:
Continue.
I’d only expect a slight (inconsequential) difference for intent for near total gross resection, because other trials typically only include accessible tumors.
Remember, the easy tumors to remove are not the ones DCVax-l works best on. Instead, mesenchymal tumors are more infiltrative and tend to jut out in various places. This is probably why you still see many partial resections in the DCVax-l trial.
Whereas the Survax trial takes an MRI three days after surgery and excludes anything that isn’t proven to be a total or very near total resection. That just seems like a blatant way to increase survival, and therefore requires a placebo controlled trial, because there aren’t external arm control possibilities.
Clarification. SurVaxM does have a phase 2b trial that started in November 2021 and intends to complete August 2024. NCT05163080
247 enrolled patients.
This is a triple blinded trial. However as you can see, they don’t merely want intended near total gross resection. They only want proven total or near total gross resection. This will also cause both arms (placebo and treatment) to have higher survival, (as it also did the single arm in the phase IIa study)
MRI within three days after surgery must show:
Thank you. That’s what I thought.
In that 64 patient Survax non-randomized trial phase IIa trial, for nGBM, 13% of enrolled patients did not have GBM, and they enrolled more mgmt methylated than unmethylated. Their graphs readily show these two factors alone very much account for their combined survival results of median 25 months.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995096/
They have many years in front of them before they’ll complete their phase iii trial. It won’t be loaded with idh1 mutant and overloaded with methylated mgmt.
Edit:
Yes, I was lazy and didn’t use a graphic arts editor. However, now consider, in the Car-T trial, that arm 5 was:
1. A little bit younger than arms one plus arm two.
2. Had a little less actual GBM.
3. Had 15% more Grade 3 gliomas.
4. Had a 90 KPS average (but arm 1+2 had 80 KPS)
Then notice the real comparison.
Arm 1+2 had 6.9 months median survival for actual rGBM whereas Arm 5 had 10.2 median months for actual rGBM.
So it makes sense they are going for arm 5 in the next (phase 2) trial.
Oops. I made a reading error. While it’s true that arm 5 (dual car-t) had those advantages, arm five did still have better rGBM median survival than arm 1+2.
So it makes sense they went with arm 5.
Glad you are on the mend.
Google Gemini:
Chat GPT:
The reality is independent directors often own a large amount of shares before being brought on board. That is a good thing as they would have skin in the game. Independent, means independent from management considerations.
LC knows this, he’s been told this, but now he’s again trying to turn a likely positive into a negative.
Best wishes with your surgery.
You just called yourself an idiot. You might slow down and remember to change handles.
Just one last comment on that Car-T trial. If you subtract the patients that were not GBM (Aka Grade 3 and/or idh mutation) there was only one possible partial/complete tumor response, and Senti has analyzed the problems with that one, aka: at best two to three month tumor response, but even that might be questionable.
Note: 25% or more in that CarT trial did not have GBM
Car-t trial: See arm results below. Arm 5 supposedly did the best, but the two longest living patients did not have GBM (they had idh1 mutation). So did one of the two longest living in arm two. The eyeball test says arm 2 and arm 5 were about the same. Again it looks like the patient whose study you analyzed, is patient 109 from arm two. If you take out the idh1 mutation patients from this trial (not GBM), no one lived four years, and just one patient out of 65 lived over 36 months. They wanted to show their elaborate administration and new manufacturing test in arm five was better, so they did some mumbo jumbo combining of arm one and two so arm two was not directly compared to arm five for survival purposes, but again, you can see it clear as day in the chart below.
https://www.nature.com/articles/s41591-024-02875-1.pdf
Note: I think your second question was answered by antihama.
Read these two posts.
681765
681880
Eden is not the initial plan. Period.
Doc, are you back on the kick that NWBO will start with Eden instead of artisan? That’s not the plan.
Continued. Car-t Correction, it might have been patient 109 in the trial, I didn’t see that faded thinner line before. He lived 18 months. His partial and complete “responses” were judged by a different standard than the others. See the key.
Again, why didn’t you use his chart from two days after that?
Here:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174133343
So negative. Maybe you should have used his chart from two days after that.
Here: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174133343
Continued: You’ll note, that car-t patient’s case study they pulled from the data had idh1 mutation.
See UPN 265, page 6.
Note: It’s no longer considered GBM
You can’t follow.
I already addressed your question, you’re so self-centered, you think this last part of the thread has something do with your question. Instead, this is about a different car-t trial with a different therapy. Specifically a case study on one patient from a larger car-t trial, not targeting egfrviii or egfr wildtype.
Senti, here is the 65 patient Car-t trial that patient’s case study was pulled from. I think you’ll locate more info about him from some of the charts. https://www.nature.com/articles/s41591-024-02875-1.pdf
Note: there were two partial responses, and one complete response according to the article.
Note: rGBM median survival in that Car-T trial was 7.7 months.
Note: Clinicaltrials.gov,NCT02208362, if you scroll down after selecting results submitted, you’ll see the submitted results were returned and not posted after quality control review.