In terms of solid tumors (eg breast cancer): PFS measures the time until the tumor grows; DFS measures the time until the cancer returns after having been eliminated.
"There has been a suspiciously large number of changes to the ACT-IV site in the past two weeks..."
1. I see 5 changes in the month of July. The monthly changes prior to that were 1, 4, 4, 1, 2, 4, 1,2, 4, 2, 8, 5, ...
Five changes in the past two weeks is a high rate but not exceptional compared to the rate in earlier months
2. Besides the email or spelling corrections, some of the changes in the past two weeks were to change the status from "Not yet recruiting" to "Recruiting"
or to add new centers to the study. That doesn't look like a sign of a shut-down to me.
"Start the CVR clock "
Wind it well because we are still 2 years from when sales will be relevant.
Maybe if SIVEXTRO gets of fto a good start Cubist will bump up the current very low probability these CVRs will pay anything.
As the maximum amount is $2/CVR, I'd say you are quite the optimist.
The last estimate from Cubist was only a 4% chance of getting the full amount, and 6.5% of getting the minimum of $1.
I kept a few rights just for grins.
"...RGDX will be testing for is, you got it, EGFRIII mutations! "
You got the wrong EGFR mutation - EGFRVIII is not included in the screening.
Does this mean the NCI is not serious?
Fraz, you and the OP see "EGFR mutation" and immediately assume it refers to the only mutation you have heard of - EGFRVIII. While v3 is important in glioblastoma. it is not a player in lung cancer. When one talks of EGFR mutant in this setting everybody but this message board understands that does not include v3.
The RGDX contract is to screen early-stage lung cancer patients for two other EGFR mutations (EGFR exon 19 deletion, L858R mutation) along with an ALK mutation as part of the ALCHEMIST trial. If the tumors are positive for one of the mutations they then go on to the appropriate treatment trial. Again, there is no screening for EGFRVIII.
My NCI joke flew right over your head also. If the OP feels that the NCI is serious because he believes RGDX will be screening for EGFRVIII it then suggests that the NCI is not serious because, in actuality, they are not screening for that mutation.
BTW: Dana Farber is just one of many centers in the study and does not have a preferred position.
It's crazy as #$%$...
2 years ago..$5/share...enterprise value under $100 million and all this board could talk about was all the cancers rindo would treat and the billions from the orphan drug 1135. Now those two options are gone and it's a billion dollar company.
"Given that cancer immunotherapy takes a while to kick in (unlike small molecules), the first look at 50% events may be too early..."
That gives hope to the first 50% event-sufferers: just give the therapy more time.
Your first sentence is spot-on, and one can estimate just what "robustness" is required. The time to kick in, however, makes no difference in this context.
As for the sales force - this topic comes up every few months. Perfectly natural to start assembling a force years before expected approval. Allows the companies to quickly start sales if trials are successful. History is filled, however, with examples of expensive failures after hiring.
Even worse is if the company had already built manufacturing facilities in anticipation of sales.
Remember Synergen? A hot stock in the 90s after positive Phase II results in sepsis convinced many that Phase III would be a breeze. An interim analysis stopped that trial for futility. Sales team was let go and a $40 million new plant closed.
Congrats on your new job as treasurer. Is that your cat that is bothering Melanie?
"The compassionate use of Rindo over the years in recurrent GBM"
Weren't at least half of those cases newly-diagnosed GBM?
CLDX has only informally described the compassionate use of rindo in conferences. Only one case was recurrent disease. For at least one other patient the GBM was newly-diagnosed.
"I'd be surprised if the emphasis was on newly diagnosed in the compassionate setting for this presentation though"
I bet you a shiney dime that at least half will be primary, not recurrent.
"Across the three Phase 2 studies, Rindo eliminated EGFRviii expression in 26/32 recurrent tumors."
Careful - don't turn into a Frazzano and keep pasting non-relevant material. next thing you know you'll be writing mostly in capitals.
ESMO 2014 Press Release: Immune Checkpoint Inhibitors Provide Antitumour Activity Across Malignant Diseases
"There are at least eight anti-PD-1/PD-L1 antibodies in clinical development, spanning phases I to III. These include nivolumab, pembrolizumab/MK-3475, pidilizumab and AMP-224 targeting PD-1; and BMS-935559, MEDI4736, MPDL3280A and MSB0010718C targeting PD-L1. In addition, the preclinical and early clinical development of inhibitors against other immune checkpoints, such as TIM3, LAG3 and VISTA, and against costimulatory molecules, such as OX40 and CD137, are underway."
For those who cannot access the article, the original ASCO posters from 2010 available at CLDX website contains most of the key points.
Some things to remember from when the data were first presented:
1." PFS =18.0 wks for pts with gpNMB"
Strong selection bias here as the tumors of less than half the patients were tested for GPNMB and these patients were selected based on performance on the trial. If you look for GPNMB in only the best performing patients then where you find GPNMB you will find the best performers.
As was later discovered in EMERGE, GPNMB expression is quite common in this population so most of those patients in this early trial who performed poorly and did not have their tumors tested were in fact likely GPNMB positive.
2. "- ORR ranged from 15% to 33% depending on dosing"
The 15% is at the dosing picked for latter and from the overwhemingly majority of of patients. The 33% is for just 2 of 6 patients at a more frequent dosing schedule.
3a."doc would use when ALL ELSE HAS FAILED"
You know docs dosing above MTD? Is that after they fail at the approved dose?
3b "exceeding MTD so they were TRAIN WRECKS"
The patients did not receive more than the MTD because they were in any worse shape than the other patients. Just bad timing on their parts to enter the dose escalation phase at the end.
1."so they the DOCS pushed the MTD to very high levels "
The DOCS pushed because that is what the protocol in the trial called for.
The deadly doses were 16 to 25% higher than the MTD.
2. "they died of Complications of Chemotherapy not nesceassarilly of Immuntherapy"
Indeed, the patients had ceased any previous immunotherapy regimens and were taking only the chemotherapy (targeted) that is Glemba.
3. "keep in mind they get COCKTAILS of drugs"
Not while they are in the trial. The investigators did not think it so hard to believe the deaths were related to Glemba.
4. "Sepsis related deaths are uniformly related to CANCER routinely,,"
Not so much for melanoma. When it does develop, blame neutropenia (a side effect of the treatment) as was the case here.
"highly volatile until REACT results are out" " until then expect the pps to linger "
How can a stock be highly violatile while lingering?
No, not a major concern to investors.
No, the accelerated approval trial has relatively easy endpoints.
Your strategy of buying all antibiotic firms has served you well.
Can you tell me when DRTX expects the EMA to have a decision on dalbavancin?
The latest treatment targeting EGFRVIII that Duke is trying to sell - EGFRvIII-targeted BiTEs
- We have solid patent protection on targeting
- Interest from Merck, BMS, Novartis, Amgen,
Treatment with i.v. bscEGFRvIIIxCD3 yielded extended survival in mice with well-established intracerebral tumors (P