Scancell Share Discussion Threads

[inanaco] 26/4/2024 14:30

so its a 3 year look

The combination of the personalized cancer vaccine and Merck's blockbuster immunotherapy cut the risk of recurrence or death of the most deadly skin cancer by 49% compared with Keytruda alone in the midstage trial, the companies said.
The results come at a median point of three years into the study involving 157 patients with stage III/IV melanoma whose tumors were surgically removed before being treated with either the drug/vaccine combination or Keytruda alone with the aim of delaying disease recurrence.


A year earlier, the study had shown a 44% reduction of recurrence or death.
"The durability of the responses is really strong, they're essentially rock solid through this time," Moderna President Stephen Hoge said in an interview. "This is a pretty significant improvement, a pretty dramatic improvement over standard of care with just Keytruda alone."

[inanaco] 26/4/2024 14:27

this is at two years with Bristol Myers

hardly any difference using doublet therapy

we know that we synergise perfectly with both yervoy and opdivo and with keytruda we Started the trial with keytruda

Patients and Methods
In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup.
Results
At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients.

[inanaco] 26/4/2024 14:15

if they use a cut of period say 1 year the 55% on the keytruda arm would rise giving less margin to the vaccine

[inanaco] 26/4/2024 14:07

Bermuda post

SCIBI has produced some fablulous results in the adjuvant setting albeit in small numbers in a single arm trial but as a monotherapy. The issue I have with comparing the 49% from the Moderna vax's with SCIB1 lies with that 49% fiigure. If it represented the RFS rate of the Moderna arm of the trial then I can see how you might start to make a comparison, but it doesn't. It's the improvement in the likelihood of a recurrence compared to the results produced by Keytruda alone. So in that trial the Moderna patients were 49% less likely to have recurrence compared to the patients on the same trial receiving Keytruda alone. We have absolutely no clinical results from SCIB1 to compare that with.

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all you have to do is look at the keytruda monotherapy trial

In the overall intention-to-treat population, pembrolizumab was still associated with longer recurrence-free survival than placebo (5-year rate of recurrence-free survival, 55.4%



correct me if i am wrong take 100-55 = 45 then if you take 49% of 45 you get 23

23 plus 55 gives you 78% ORR

as against scancells 75% as a mono therapy (5/20)

add the synergistic effect of PD-1 you can easily better moderna trial

while cutting costs by an enormous margin

what our current trial is proving 88% of patients had a t cell response in the adjuvant settings

so potentially that is your margin if the orr of 85% is maintained, but HLA restricted which the moderna isn't

ISCIB1 data is the key as that is not HLA restricted

[inanaco] 26/4/2024 13:06

if your sitting at a desk sleepy while working a Bristol Myers

and the phone rings

we have data that shows we have synergy with Opdivo and yervoy showing 85% ORR with SCIB1

can you help with

Ovarian cancer with Modi1 ?

if renal cancer using the doublet therapy worked ?

the big boys need market penetration as much as scancell does

only Scancell has something that they need "efficacy" and synergy

those that don't take up with synergistic efficacy lose market share its that simple

[inanaco] 26/4/2024 12:59

lets assume that moderna and merck get approval ...

and they become the standard of care

Opdivo and Yervoy left in the cold

Bristol Myers being a poor relative losing business thinks ....

we want that market .... SCIB1 tested with our product is stunning ...

Ok .. make a move

[inanaco] 26/4/2024 12:55

if it was the case that first to market wins ...

adjuvant melanoma with checkpoint only would remain standard of care

the vaccine would not get a look in

indeed how did the checkpoints get a look in ?

[inanaco] 26/4/2024 12:53

octupus because its a phase 3 study !!

scancells phase 2 study had patients on the BBC

[octopus100] 26/4/2024 12:50

I'm not criticising the company just pointing out they are not only one in this space and sometimes its first to market that wins.
I also dont understand how a company like this in the press today gets so much publicity when Scancell in the same space and by feedback of trials so far is getting better results than anyone else doesn't get the same publicity.

I also don't understand why takes so long to recruit people for trials. If I had late stage melonoma and there was nothing else to do - I'd sign up for this trial straight away.

[ivyspivey] 26/4/2024 12:38

As you say Octopus there are challenges to SCLP.
However to some All in the garden is Rosy and SCLP cannot do anything wrong.
Must admit some of us questioned that mantra which has been prophesied for at least 10 years and have benefited from that decision.

[inanaco] 26/4/2024 12:14

potential investments

Modi1 .... will have a defined route to market by 2025

SCIB1 defined but could also run a adjuvant setting cohort

modi2

Glymabs

all eats cash

you can see that just having cash how long it takes to get into trial

Genmab are loaded .... ??

so to get all this products lined up for trial that scancell has is pretty good going

[inanaco] 26/4/2024 12:03

Problem is not Scancell but funding .....

[octopus100] 26/4/2024 11:52

Really need to get on with the SCIB/iSCIB trials - as in the press today someone trialling a personalised melanoma vaccine. Albeit it personalised still impacts scancell if they are successful and first to market.

[inanaco] 26/4/2024 11:43

now in relation to the current trial ...

this bit is very interesting

1/ SCIB1 induced dose-dependent T cell responses in 88% of patients with no serious adverse effects or dose limiting toxicities. The intensity of the T cell responses was significantly higher in patients receiving 4 mg doses without tumor when compared to those with tumor (ρ < 0.01)


current 85% ORR v 88% vaccine t cell response

[inanaco] 26/4/2024 11:33

In conclusion, SCIB1 is a novel class of anti-cancer immunotherapy that induces T cells which can cause tumor regression in patients with melanoma. The high frequency of
responses, their breadth and durability suggest SCIB1 is worthy
of further study in a larger cohort of patients. This is particularly the case in the adjuvant setting, where all of the patients
responded immunologically and where absence of toxicity is
an important clinical consideration. Furthermore, the stimulation of potent de novo immune responses by SCIB1 may provide an opportunity for synergistic combination therapy with
checkpoint inhibitors in late stage disease

[inanaco] 26/4/2024 11:32

Bermuda asks "So how can you compare at this stage?"

1/ SCIB1 induced dose-dependent T cell responses in 88% of patients with no serious adverse effects or dose limiting toxicities. The intensity of the T cell responses was significantly higher in patients receiving 4 mg doses without tumor when compared to those with tumor (ρ < 0.01)

2/
5/20 fully-resected patients have experienced disease recurrence but all remained alive at the cut-off date with a median observation time of 37 months. A positive clinical outcome was associated with MHC-I and MHC-II expression on tumors prior to therapy (ρ = 0.027).

we don't need to compare SCIB1 produced a better result without CPi v moderna

because we know that CPI IS SYNERGISTIC with our vaccine proven from our current trial and that our current trial is able to control disease progression from adjuvant patients stands to reason that, current standard of care ie checkpoints in adjuvant melanoma where treated with a half dose of SCIB1 the results would be very high efficacy

why ?

because all secondary melanomas are the same ... melanoma

and scib1 has been shown to work in all settings



Bermudashorts

Posts: 12,623

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No Opinion

RE: MRNA melanoma trialToday 10:01
Ee

I apologise if I should have understood that from your post but it wasn't obvious to me because SCIB1 has never been trialled in this setting - ie. in combination with PD-1 CPI in the adjuvant setting. So how can you compare at this stage?

Keytruda is approved as an adjuvant therapy in melanoma and the Moderna trial was a randomised study with Ketruda alone as the control arm versus Keytruda plus the Moderna Vax. So the 49% figure is the reduction in the risk of recurrence/death when taking the combination versus treatment with Keytruda alone.

That is the whole point of my last sentence - if the phase III study is successful it validates the combination setting for cancer vaccines.

[inanaco] 26/4/2024 11:01

now if you want to test the dice in a bigger trial ....

increase the number of sides to 1000

make 85% green and 15% red

roll the dice

if 70% of the outcome is Green ...

the probability of 90% is proven

ATB

[inanaco] 26/4/2024 10:54

considering you keep telling us this is your job .... you really are making a pigs ear of it

Bermuda was just plain wrong ..... but will not accept it

You can use probability to predict outcomes regardless

that is how Phase 3 drugs are actually approved ... a predicted score in the real world setting

[inanaco] 26/4/2024 10:50

Ruck its a good job Einstein with his theoretical maths did not listen to you !!

but let me explain Heads is efficacy v tails is no efficacy .....

so weight is added to Heads .... causing the coin to flip to heads in the majority

try another way a dice ............

it has 11 sides 9 sides are marked Green for efficacy 2 are marked red for failure

scancells probability

Now roll the dice and record the outcome


RuckRover26 Apr '24 - 07:06 - 7993 of 8002
0 0 0
Inan,

Once again you totally miss the point.
The chance of getting a head in a coin toss is 50%. That is the maths and the maths IS correct. If you toss 10 times and get 4 heads (40%) it doesn’t mean the maths is wrong, the probability is an indisputable mathematical fact.
There is no way the 90% can ever be proven accurate.

[inanaco] 26/4/2024 10:32

and the way it works is the Betamax would be the standard of care and you have to statistically beat it .... on safety as well
then it gets adopted

[inanaco] 26/4/2024 10:30

there is no VHS to compare with MT at present

[markingtime] 26/4/2024 10:12

The biggest danger is indeed getting left behind. Cost advantages should help in that, but we don't want to be the Betamax when the world has adopted VHS....

[ivyspivey] 26/4/2024 08:47

Plus whole Keith Flaherty contact all those years ago