Replies to post #182317 on NorthWest Biotherapeutics Inc (NWBO)

[Lykiri]

JUNE 29,2018
Article: Combination of Immune Cells Improves Chances of Successful Immunotherapy.

“Krummel’s lab found a kind of immune cells called stimulatory dendritic cells (SDCs) were required for more robust T-cell responses. Without SDCs, T-cells were unable to respond effectively to checkpoint inhibitors.
However, for SDCs to be recruited and survive within tumors, another kind of immune cells was needed. Those are the NK (natural killer) cells, and usually act as first responders to detect cancer cells.
“One of the fascinating discoveries here is that we’ve long known that natural killer cells — as their name implies — can also kill cancer cells directly,” Krummel said. “But here we are discovering that their power doesn’t lie just in their ability to eliminate threats, but also in their ability to communicate with other immune cells.”

https://immuno-oncologynews.com/2018/06/29/combination-immune-cells-improves-immunotherapy-success/

[survivor1x]

Exactly!!!

Imagine a chart for 100 patients in each arm where the median OS is better for the treatment arm 24 months vs 16 months.

Better median right?

What if patients 49 through 100 lived at least 5 years in the placebo arm and patients 49 through 100 all died in month 25 in the treatment arm?

The point is the median is only 1 piece of the puzzle. The detractors will try anything to not use better measurements of treatment success and it's clear the company is trying to capture a full data set. They need to give us guidance on what full means though.

[longfellow95]

Lykiri.

Thanks for this.

It demonstrates the limitations of a time-to event median very simply. The first 'Median Duration' graphics show how the median can be the same for each arm, but does nothing to demonstrate what happens beyond the median.

So, delayed response can be largely missed, and long tail survival will be completely missed.

So to reflect those treatment kinetics, the video then shows how timepoint analyses (milestone analysis) can add useful input, which in turn allows you to compute a more accurate Relative Risk Reduction, and Hazard Ratio.

So if someone is wondering about whether a 3 or 4 month difference in median OS will be sufficient, the answer is probably no, but if it is augmented by post-median milestone analysis which defines the long tail, enabling a Relative Risk Reduction/Hazard Ratio calculation, then a more accurate and favourable p value can be demonstrated.

Now in our case, obviously a balance has to be struck. OS48 would be an even better measure of RRR, than OS36, but that would be a bridge too far.
So, yes, the case for going to OS36 (percentage milestone survival at 36 months) is very apparent (to me at least.)

Now to be honest, time from randomization is the nearest thing to an industry standard, which means we might just hit the end of the year before topline can be announced.

Which means we have another six months of bear sentiment, telling us ad nauseam that the trial should have already finished.

When it is actually quite simple to see the benefit of going to OS36!

So thanks for that Lykiri, and I recommend any doubters to look at the video and understand it, because it shows graphically why there is potentially, critical additional value in going a few more months.

(Ignore the fact it is produced BMY!)

[Lykiri]

Some lessons we can take from the study below:

Quote:

“The results of the INTELLANCE 2 trial presented in November showed that those treated with Deputax-M in combination with temozolomide (TMZ) possibly did slightly better than those treated with just TMZ alone. However, these results were not significant enough.

The most recent results, presented at ASCO, include an additional few months of data and indicate that the difference in survival between the Depatux-M and TMZ combination versus TMZ alone is greater than originally shown."

Quote:

“However, because the INTELLANCE 2 trial had already been 'unblinded', meaning that the researchers and participants found out who took which treatment, the company cannot use these results to file for regulatory approval. “

Quote:

"These developments demonstrate the challenges faced by companies, as they have to balance the risk of reporting trial results too soon against the curiosity of understanding whether a treatment works."

https://www.thebraintumourcharity.org/media-centre/news/research-news/positive-results-recurrent-glioblastoma-drug/

Positive results from a drug treating recurrent glioblastoma.

Thursday 28 June 2018

New data presented at the recent American Association of Clinical Oncology (ASCO) meeting in Chicago by Abbvie, a pharmaceutical company, provides hope for those diagnosed with a glioblastoma

In November 2017, Abbvie presented results of their phase 3 clinical trial, called INTELLANCE 2, at the annual Society of Neuro-oncology meeting. This trial tested a drug called ABT-414 or Depatux-M on individuals with relapsed glioblastoma.
The drug is composed of a combination of an antibody—a type of a protein produced by the immune system—to target EGFR, a type of tumour marker, and a substance that when released inside tumour cells causes them to die.
The results of the INTELLANCE 2 trial presented in November showed that those treated with Deputax-M in combination with temozolomide (TMZ) possibly did slightly better than those treated with just TMZ alone. However, these results were not significant enough.
The most recent results, presented at ASCO, include an additional few months of data and indicate that the difference in survival between the Depatux-M and TMZ combination versus TMZ alone is greater than originally shown.
The difference between the two treatments has increased as the data 'matures'. This means that those treated with Deputax-M and TMZ combination have shown better survival than those who were treated with TMZ alone and this difference shows up more over time.
Whilst the median overall survival shows a modest but significant increase from 8.2 months to 9.6 months, over 20% of those receiving the Deputax-M and TMZ combination survived over 2 years, compared to under 3% of those receiving just TMZ.
In addition, the Deputax-M and TMZ combination also performs very well in those individuals who have received TMZ more than 16 weeks prior to treatment. In these circumstances, median overall survival improves from approximately 10 months to 15 months.
However, because the INTELLANCE 2 trial had already been 'unblinded', meaning that the researchers and participants found out who took which treatment, the company cannot use these results to file for regulatory approval.
Fortunately, Abbvie are currently carrying out another clinical trial called INTELLANCE 1 that is testing Deputax-M in patients with a newly diagnosed glioblastoma. The results from this trial, if positive, can be used to file for approval from regulatory agencies.
These developments demonstrate the challenges faced by companies, as they have to balance the risk of reporting trial results too soon against the curiosity of understanding whether a treatment works.
Thankfully, in this case, Abbvie are making Deputax-M available through their compassionate use scheme, meaning that people this treatment. with a recurrent glioblastoma can speak to their clinician about accessing

[Lykiri]

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma


Journal of Translational Medicine201816:179
https://doi.org/10.1186/s12967-018-1552-1
© The Author(s) 2018
• Received: 8 June 2018
• Accepted: 19 June 2018
• Published: 29 June 2018

The original article was published in Journal of Translational Medicine 2018 16:142

Correction to: J Transl Med (2018) 16:142 https://doi.org/10.1186/s12967-018-1507-6

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.
Incorrect author name upon publication:
• Tobias Walpert
The correct author name:
• Tobias Walbert
The affected sentence in the Methods section upon publication, with the error marked in bold:
• In general, approximately 2 g of tumor tissue was needed to produce the full ten doses for the 36-month treatment and follow-up schedule. The vaccine was aliquoted in individual doses and cryopreserved at?<?150 °C [22].
The corrected sentence, with the corrected temperature marked in bold:
• In general, approximately 2 g of tumor tissue was needed to produce the full ten doses for the 36-month treatment and follow-up schedule. The vaccine was aliquoted in individual doses and cryopreserved at?<?-?150 °C [22].
The reference which is cited in the above sentence can be reviewed in the original article.