The Eisai-sponsored Lenvatenib study in RET driven NSCLC P2 trial is currently designed & funded to recruit 1000 pts with an indicated data lock date later this year. Sounds like a registration - sized trial. Think EXEL is doing enough to stay competitive?
As part of my wife's birthday gift from last December, I bought us 4 tickets to a concert we just attended last nite - Elvin Bishop and James Cotton at the Cascade Theatre in Redding Ca. It was a really big deal for us to get out like that with friends. If I am a student of anything, I am a student of the blues.
JC was fresh from a Grammy nomination in LA & used a cane to access his stage seating. Elvin has not aged an iota in two decades. His backup included an old & unexpected AZ acquaintance on keyboards. Absolutely, luminously, tubular...
We partied very hard. If partying is an academic endeavor, count me in...
Ernie, does RET fusion NSCLC strike you as an indication Cabo will eventually "step" into...
Or do you see broader strokes being cut...??
With the NCCN meeting this month (abstracts - of course - closed to public)...do you see anything thing potential OL sleepers? What's yer take on the suspended cholagiocarcinoma trial?
Care to read anything into that?
"I understand how it happened. The bone thing is unique..."
Ernie, you can be a master of understatement.
Not only did the "bone thing" draw the attention of the investment community, but it got the attention of the best and brightest thought leaders in all of investigative cancer research. After 3 years of observation and analysis, $10's of millions in NIH funding, and thousands of additional trial hours...what more do we know about the Cabo bone phenom since it was first presented?
The BJC has published that it represents a "favorable therapeutic benefit'...
Doc deBono has told us the effect suggests "tumor-specific cell death"...
Doc Vogelzang has told us he expects Cabo's bone effect will change the way CRPC is treated...
The whole bone effect package fits nice and tidy into Doc Scher's proposed CRPC biomarker assay...
Doc Higano is recruiting her third round of Cabo research ( can't wait to hear what she says next...)
Since I first drank the Cabo Koolaid, trials have expanded from a handful to over fifty. Cabo stands to represent one of the most profound impacts on cancer therapy in over a decade, and a great portion of that perspective is based upon the uniqueness of the bone phenom and all that it represents. Cabo's greatest misfortune to date has been that the dosing considerations were lengthy, but the greatest obstacle yet to overcome is the relative naïveté of the regulatory pathways...and the infancy of the requisite biomarker sciences. It'll all fall into place...I'm very optimistic.
It's simply taking a bit longer than anyone could have anticipated.
Right again. Wrong again.
Home again Finnegan.
Smarmy is all you are ...right or wrong.
Nice find, Bif.
I wouldn't be too hard on the decision as to which of the "low-hanging fruit" was ripest for the picking...
Compelling as the aggregate broad-spectrum RDT results have become - broad-based, broad spectrum validation has become every bit as compelling...and appears to have withstood the clinical scrutiny.
A recent protocol change to the Cedars-Sinai visceral mets study (PI E Posadas) to actually include the verbiage of studying CTC profiles utilizing their "NanoVelcro chip" got me to thinking that - in the eventual wake of Cabozantinib's clinical acceptance as a multi-indication therapeutic "tool", many biomarker concepts & technologies are "standing in the wings" awaiting co-validation.
This comes with a price tag: the status quo technologies stand to be compromised, making way for the new. The Veridex Cellsearch might no longer be the stand-alone CTC enumeration platform, and may actually become a dinosaur, relatively speaking. Perspectives on biomarker analysis and regulatory acceptance will face many challenges, as Cabo response is as yet supported by many that - to date - have little regulatory relevance. Interesting times lay ahead...and your find brings further optimism to the table.
"I can't leave you people and MMM alone for a minute."
Ain't that the truth...
Actually, since you've been gone, we figured to blame this one on you!
Next time you decide ya just gotta take time off to elope...give us some freekin' notice...
I'd begun to think you'd been kidnapped by the Darkside.
Unless - of course - you believe the two are one and the same.
Duffer, you have a pretty good handle on this situation, and I really appreciate your inputs.
The next 90 - 120 days should provide quite a ride with a lot of entertainment value.
Here's wishing EXEL's long-patient longs all find a chair when the music finally stops...
"When would you expect results from Comet 2..."
The only answer I'm comfortable giving you is the one that applies. The database will lock 12 weeks after the final patient is dosed to check for pain response durable from week 6. No calendar date applies. I'm disappointed (and a bit surprised) that this trial has been so slow to recruit. I actually anticipated slow recruiting in Comet 1. due to the patient commitment to a prednisone-only cohort without provision for crossover. I got that one exactly bass-ackwards...
"Two secondaries in about two months is pretty unlikely."
I agree, but had to say it...only because it is most representative of the management support EXEL shares have seen in recent times. It's a departure from what I expected this month, but I'm not discouraged. I'm convinced that this undue manipulation has to end at some point, and we see what happens when the rubber finally hits the road.
This recent drop seems as though it is all part of a carefully contrived strategy to enable another wash, rinse, and repeat cycle before news is announced. The Comet 1 interim is a wildcard based on # of events, but Comet 2 is essentially calendar based, and endpoint dataset closure is based on 12 weeks beyond first dosing of the final patient. I figure that for the final signal for the convert manipulators to be on-board here...
Scary, though... I keep looking for MMM to announce another low-ball dilutive offering. It'd sure be in-line with his financial strategy to date.
Something is up, but I don't think it is Cabo - specific. It may be a drug-class issue in this indication. Take a moment and Google "Does Vandetanib cause cholangiocarcinoma?
A couple of interesting pieces in today's JCO early release I consider worthy of note.
"CTC counts Prognostic of OS n SWOG# mCRPC P3 Docetaxel w or w/o astrasentan" -.A Goldkorn et al..
...and an accompanying editorial by Terence Friedlander, "The End of the Beginning: CTC's in CRPC"...
Good commentary...Docs Higano and Vogelzang are coauthors in the SWOG study.
Just a heads -up...Journal of Thoracic Oncology March 2014. I don't see anything particularly compelling with these results, but was admittedly surprised to find anything new in publication on EXEL's PI3k program. Below are the results of a P1 dose-finding study w/ Tarceva.
The MTDs of SAR245409, in combination with erlotinib 100 mg QD, were 70 mg QD and 20 mg BID. The most frequently reported treatment-related AEs (any grade) were diarrhea (35%), rash (35%), and nausea (28%). No treatment-related AE occurred at grade 3/4 in more than one patient (2.2%). No major pharmacokinetic interaction between SAR245409 and erlotinib was noted. Suppression of PI3K and EGFR/mitogen-activated protein kinase signaling pathway biomarkers was observed in skin and tumor samples. Stable disease was the best overall response reported, occurring in 12 of 32 (37.5%) evaluable patients.
MTDs of SAR245409 and erlotinib were below the single-agent doses of either agent, despite the lack of major pharmacokinetic interaction."
This is not to be construed as "new" news.. let me clarify a bit.
I've posted it because these trial results are not only important to EXEL, but it is also important that these results are published in a peer-reviewed setting. Pubmed and Cancer Discovery have both enabled the peer review process, and the message is clear...the combo has very high efficacy.
But a caution is warranted...the space has become crowded. The dabrafenib/trametinib combo has received a priority blessing, and the Vemurafenib/Cobimetinib combo may take some time to play catch-up. Personally, I believe it displays a beneficial advantage, but that may take some time to tease out as the data matures. The additional post regarding V vs D is also worthy.
Update on Vemurafenib vs Dabrafeninb...Annals of Oncology March 2014, B Schilling et al...
"In this study, we demonstrate that vemurafenib but not dabrafenib reduces peripheral lymphocyte counts in melanoma patients while both agents show similar clinical efficacy. Within the lymphocyte compartment, vemurafenib selectively decreases circulating CD4+ T cells and changes their phenotype and function. This indicates that selective BRAFi need to be assessed individually for immunomodulatory effects, especially, when planning combinations with immunotherapies."
Pubmed 3/3/14, EPub ahead of print..
"We hypothesized that combining vemurafenib with a MEK inhibitor would inhibit ERK activation in the melanoma and prevent ERK activation by vemurafenib in the leukemia and thus suppress both malignancies. We demonstrate that intermittent administration of vemurafenib led to a near-complete remission of the melanoma and the addition of the MEK inhibitor cobimetinib (GDC-0973) caused suppression of vemurafenib-induced leukemic proliferation and ERK activation. Anti-melanoma and anti-leukemia response have been maintained for nearly 20 months...'
Interesting that I posted earlier on Zoledronic acid. Went looking, and found this...
Medscape 3/6/14, Megan Brooks... Trial results are in the JCO.
SRE's may become an important issue in Cabo's future.
"If Comet 1 fails and Comet 2 succeeds, then what?? Could Comet 2 rescue the program?? Then we start splitting hairs and looking at all the details. A lot factors that would not have mattered suddenly become very important."
This is exactly the salvage scenario that has prompted me to keep a large core holding here. The CRADA/CTEP/IST support program has grown to an extraordinary allocation of trial financing, and the trove of clinical information that could be released in the coming two years has potential to unveil catalysts that we haven't even begun to consider. MMM has told us we're paying too much attention to the BSR data. Well...OK...omit the bone scans. What about all the other OS supportive data? On the horizon is a newer zirconium-based radio-label PET that is being touted as light years ahead of all known imaging modalities. Let's throw that baby into the mix, and see how Cabo flies...
My point is this...All the theoretic survival indicators to date have proven positive, and we have yet to actually determine the lowest known effective dose, particularly given the potentials of synergy in AR combination at earlier stage of disease progression. I am still very optimistic for a favorable review of Cabo benefit on the tumorous micro-environment, and feel that the support of the clinical community is still with us.