Replies to post #212994 on NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

Interesting.

So this trial is measuring Nivo + Bev (Avastin) and Nivo + low dose Bev in Recurrent GBM.
https://clinicaltrials.gov/ct2/show/study/NCT03452579#contacts

And this trial (also a P2) is measuring Nivo + Bev vs. Nivo + low dose Bev in Newly Diagnosed GBM.
https://clinicaltrials.gov/ct2/show/study/NCT03452579#contacts

The primary endpoint for the newly diagnosed GBM trial is OS at 12 months.
Secondary is OS at 3 years, + ORR + DOR + PFS - all at 3 years + PFS at 6 months

They are doing another P2 trial in unmethylated newly diagnosed GBM using Nivo, Ipi, short-course radiation - so no TMZ with a primary endpoint for OS at one year, secondary endpoint is 2 years.
https://clinicaltrials.gov/ct2/show/NCT03367715

And also in newly diagnosed GBM, BMY is comparing SOC w/Nivo against placebo - in MGMT methylated
It's a P3 trial, with co-primary endpoints of PFS at 35 months and OS at 69 months
https://clinicaltrials.gov/ct2/show/NCT02667587?term=CheckMate+548&rank=1

First off, I find it interesting that they are measuring the primary for some of these trials, including two of them at 12 months for newly diagnosed GBM. I can understand using that time frame in recurrent GBM. The primary in the DCVax-L and Nivo trial measures OS at 12 months too.

I hope they don't plan to pull an Optune on us. At least the P3 in newly diagnosed is going out to 35 months.

[CogDiss 1188X]

Thoughts on BP throwing spaghetti against the wall

BMY are running a new randomized open-label P2 in recurrent GBM.

Two arms.

Arm 1. Nivo plus standard dose Bev.

Arm 2. Nivo plus reduced dose Bev

BMY really don't seem to have a clue..

It reminds me of 20 years ago, sifting through hundreds upon hundreds of combination chemo trial results — the brute force approach BP used, reminded me of banging one’s head against the wall, hoping for a 2.5 month survival extension, seemed like an insane way of approaching the problem. Especially in light of the fact that it was becoming obvious by the mid-eighties (after 40 years of head banging) that the chemo approach was proving ultimately to be a dead end.

But is BP, or in particular, BMY, clueless? Could be. It is run by human beings, so the potential to royally screw up is inherently present.

However, my assumption is that it is run by very highly-paid, very experienced people, some of whom may be a little light on empathy, especially the higher one goes up the ladder.

What do they hope to learn?

Beyond the main hope that some combination of markers and drugs and indications will work (ie, that some spaghetti sticks to the wall), sometimes an obviously failed strategy has a point (see Middle East wars, war against drugs, war against cancer, etc).

How so in the case of BMY or Merck?

My understanding is that BPs with ICI assets are currently running a metric shit ton of trials (unit conversion free of charge ;-) ). Merck alone is running 899+ trials involving pembrolizumab combinations (will provide link in a future post).

If p <= 0.05 is statistical nirvana then Merck may be on its way to roughly 45 successes, purely by chance. Obviously they’re not going to publish all the failed trials. Perhaps this is an overly simplistic way of looking at it but it seems like, whatever the actual number, the slot machine will pay out, even without big drug effects. Since the drugs do have effects, the payout should be fairly good.

Especially in the context of an FDA open to approving based on single-arm, early phase trials, now is the time to get in on the gold rush. Time is money and money buys time.

Perhaps it is BP that is pushing grapefruit juice.

Another desired effect of running so many seemingly pointless trials is to block out the competition, especially from small, innovative, upstart companies with their own new-fangled ICI that might be marginally better. BP has the key contacts in the hospitals and universities to give its trials dibs on the patient pool. All those KOLs in the pay to BP come in handy in various ways.

Just some thoughts...IMO and all that.

Pity the patients.

Yes, indeed.