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Exelixis, Inc. Message Board

wilderguide 392 posts  |  Last Activity: 10 hours ago Member since: Jan 13, 2011
  • $$$$
    The recent Posadas commentary posted at targetedoncdotcom got me thinking about the trial design proposed in that P2 trial, and I went looking to see what potentials might lie hidden within the "melancholia" of yet another Phase 2 Cabo trial. The following is a descriptive quote from US patent 20140056807, held by Drs Di Vizio, Freeman, and Morello - all involved in post-doctoral research at CSMC:
    "The invention further provides methods for determining the likelihood of cancer metastasis in a subject in need thereof. The method includes providing a sample from a subject that has or had cancer and detecting large oncosomes in the sample by the methods described herein. A presence and/or an increase in the number of large oncosomes in the sample from the subject relative to the number of large oncosomes in a reference sample is indicative of increased likelihood cancer metastasis in the subject."
    My guess is that they are using this oncosome detection platform in conjunction with the CSMC Nano-Velcro CTC enumeration platform to enable a peripheral biomarker survey of cabozantinib response in specifically defined patient groups. This work up could easily be of great importance to Cabo...

  • wilderguide wilderguide Jul 15, 2014 3:23 PM Flag

    $$$$
    "But no mention of OS. Without this info the rest is meaningless"
    Wrong. The existing BRAF/MEK combo of dabrafenib/trametinib got FDA approval in melanoma on a less significant PFS. What you are looking at is not only approvable PFS data, but commercially competitive data that is considerably more clinically meaningful than existing approved therapy.

  • wilderguide wilderguide Jul 15, 2014 3:12 PM Flag

    $$$$
    From interview w/ Posadas:
    "The presence of visceral metastatses is a poor prognostic indicator for men with prostate cancer.
    Seven of the 8 patients enrolled in the trial so far have experienced prolonged disease stability.
    One patient with liver metastases saw a regression of his liver disease in 12 weeks of treatment.
    Researchers of this trial are characterizing circulating tumor cells and large oncosomes in the hopes of one day eliminating the need for needle biopsies for men with prostate cancer."
    More fuel for a growing blaze, certain to fry ol' shorty's patootie. Good find, Neers87...

  • $$$$
    Here's what the oncodocs are seeing...
    Vemurafenib- Cobimetinib Combo Improves PFS in Phase III Melanoma Trial
    Silas Inman, Published Online: July 14, 2014
    GLTA

  • wilderguide wilderguide Jul 14, 2014 10:35 AM Flag

    $$$$
    Breakthrough status must be applied for..and tho it might still be a consideration with the NDA filing, but there might necessarily be a requisite comparison trial with the dabrafenib/ trametinib combo.

  • wilderguide wilderguide Jul 14, 2014 9:21 AM Flag

    $$$$
    Just thought to remind you of your post from 6/29. Keep yacking up the worthless IP...keep harping about zero shareholder equity...keep posing...
    "We are now 2 days past the Zero Shareholder Equity Day! That's right gamblers who hold shares in this BioScam. That means equity is now negative by $1,658,000 and includes that worthless intellectual property they have on the books bewildered guy tries to convince you is so valuable. The truth is he knows its junk that's why when asked his opinion on value he runs and hides screaming like a little girl. He just can't wrap his mind around the facts. Such as they booted the CFO because he ran the company into the ground. They pay hypesters because no analyst would bother to follow this company as the prospects are unimpressive. That's right. No one is commenting on the "discoveries" the mumbling research people are reporting on because nothing beyond noise relative to placebos is being recorded. How sad is that? Its funny, actually, to anyone not owning this stock."

  • Reply to

    FWIW Dept - Dr Kurt Miller

    by wilderguide Jul 13, 2014 10:10 PM
    wilderguide wilderguide Jul 14, 2014 12:56 AM Flag

    $$$$
    "The problem lies in the fact that..."
    Here's the real proble-um...and da ting is dis...
    Ya don't know da ting what it is dat ya don't know.
    I tell it to you...you tell it to your wife...she tells it to her boyfriend...
    Purty soon...all dese people - dey know da ting what it is dat you don't know...
    Now...do you see who's got da proble-um...?
    Humorless...useless...you are truly a critter without humanity.

  • Reply to

    FWIW Dept - Dr Kurt Miller

    by wilderguide Jul 13, 2014 10:10 PM
    wilderguide wilderguide Jul 14, 2014 12:41 AM Flag

    $$$$
    Right on...a nearly immediate thumbs down from the commercial insurance salesman that can't carry a credible thought to the MB even with the unified devices of a multitude of aliases. Useless dooshwaddle...
    Get a freekin life, BozoBreath...get those voices outta yer head...

  • wilderguide by wilderguide Jul 13, 2014 10:10 PM Flag

    $$$$
    I did a bit more DD on Doc Miller today, and found an interesting affiliation. In addition to his being Chairman of the Urology Dept at Ben Franklin Medical Center in Berlin, Germany, Doc Miller is also a board member of the European Skeletal Care Academy's Physician Steering Committee. The SCA strives to impart physician information targeted toward optimizing and standardizing bone care in European oncology. I encourage you to visit the SCA website at skeletalcareacademydotcom. In Europe, there is no higher source of information for oncological bone care, and this places the highest premium on Doc Miller's optimistic Asia-Pacific Cabo presentation. Even tho far removed from Europe, it's good to see he's spreading the good word on Cabo's bone phenom. I see nothing but good news in this for EXEL.

  • wilderguide wilderguide Jul 13, 2014 5:23 PM Flag

    $$$$
    Here's the synopsis posted alongside the video, Valley...look for this at ecancerdotorg.
    The still of Dr Miller is right alongside this summary. Click on the still shot of Doc Miller. You may need to download Adobe Flash...Its there, and pretty easy to find. Titled same as is this thread...
    "Dr Kurt Miller from Berlin, Germany, looks ahead in prostate cancer. He reviews the drive for more personalised medicine and reviews biomarkers for partially prognostic and partially predictive markers, such as the composite score of LDH, neutrophil lymphocyte ratio and extent of metastases. He also considers the various genetic markers being explored, such as ERG. He then moves on to talk about potential new compounds, such as cabozantinib, OGX-011, PSMA ADC and bite molecules." GL

  • Reply to

    Cabozantinib in LADC/ NSCLC

    by wilderguide Jul 12, 2014 7:21 PM
    wilderguide wilderguide Jul 13, 2014 2:31 PM Flag

    $$$$
    You are mistaken. I never said that at all. It's simply in your nature to twist wording to suit your agenda. You'll never be anything different than the dimwit you've always been. Misquoting your MB adversaries is your least worrisome lack of etiquette, but your continued endeavor toward human pathos is absolutely and purely horrific. You are a freekin waste of good air...

  • wilderguide wilderguide Jul 13, 2014 12:52 PM Flag

    $$$$
    "Naves tore" = investors
    Darned spell checker...

  • wilderguide wilderguide Jul 13, 2014 12:45 PM Flag

    $$$$
    "...when will it happen...(?)..."
    My "in a nutshell" argument in the past has been "When the science is proven to be beneficial to patient" but I have changed my tone somewhat. I now believe that the CRPC treatment algorithm is brimming with new treatment choices - so many in fact, that oncodocs are overwhelmed with choices of order, treatment compatibility, and sequencing. Cabo will have to prove it's place, and although some insight into Cabo's MOA substantiated by bone and biomarker response is no doubt forthcoming, cabozantinib will still necessarily need to enjoin clinical acceptance in CRPC...and in view of the many recent approvals, may indeed be slower than naves tore would like to see.
    I think the most important question to ask is " Will cabozantinib become the MET inhibitor of choice in a treatment paradigm of biomarker-guided therapy?"

  • Reply to

    Cabozantinib in LADC/ NSCLC

    by wilderguide Jul 12, 2014 7:21 PM
    wilderguide wilderguide Jul 13, 2014 12:21 PM Flag

    $$$$
    Yessir. Gefitinib, afatinib, erlotinib...perhaps even selumetinib...
    I only interjected Cabo to light up Shorty...
    Looked like it worked too...usernames doesn't like to be left out.
    Nor do all his AKA's...

  • Reply to

    Cabozantinib in LADC/ NSCLC

    by wilderguide Jul 12, 2014 7:21 PM
    wilderguide wilderguide Jul 13, 2014 1:44 AM Flag

    $$$$
    Truth is we can't tell, not knowing her particular variety of mutational driver, but erlotinib does not fit the description of "new"... Far from it. In addition, the lawsuits are already beginning to fly over generic manufacture of Tarceva. It is far from "new".

  • Reply to

    Cabozantinib in LADC/ NSCLC

    by wilderguide Jul 12, 2014 7:21 PM
    wilderguide wilderguide Jul 12, 2014 9:24 PM Flag

    $$$$
    "Yeah, she'll croak and no one will care."
    This is the most socially irresponsible and ignorant statement I have ever heard.
    You are an idiot...

  • wilderguide by wilderguide Jul 12, 2014 7:21 PM Flag

    $$$$
    Just a hunch, but based in part on the lack of substantive media coverage. International lawmaker and Sen Miriam Santiago has just announced that she has been diagnosed with stage 4 lung cancer, and the media is saying very little about her treatment other than it is a new "chemotherapeutic" pill. I figure the suspense will subside over the next few weeks, and I won't have to guess any longer...

  • $$$$
    Journal of Nuclear Med 2014 Supp 1; 402...Katherine Zukotynsky, et al
    "Prognostic value of baseline evaluation of FDG and NaF PET/CT in castrate-resistant prostate cancer (CRPC): Early results from a prospective phase 1 trial"
    I don't think this study got tossed out for discussion, but I think it's important to consider future direction as it becomes available. Here, these early study results seem to indicate that - in the future - CRPC treatment groups may be stratified into three subset groups, apparently based upon metastatic staging and FDG sensitivity. Determining which of these patients are most receptive to the combination of Cabo and Abi will undoubtedly help determine the best targeting of a future P3 trial.
    GLTA

  • wilderguide wilderguide Jul 12, 2014 3:55 PM Flag

    $$$$
    In the face of ongoing expert commentary - both in publication and practice -I am increasingly confident that Cabo will find it's way into the treatment algorithm in CRPC. However, actually defining that entry point is still troublesome, though androgen resistant, heavily treated pops currently appear to hold the lowest bar for a gainful foothold. I also continue to believe that the rationale for combined AR/Cabo therapy is sound, and I anxiously await future low-dose Cabo study results with both Abi and Enzalutamide.
    Cabo really needs a predictive biomarker to enable therapeutic guidance. The literature is replete with the importance of cMET inhibition in treatment-resistant cancer therapy, but the predictive mechanisms to ensure patient response have proven elusive. Should Comet-1 fail to achieve it's endpoint of statsig OS, I remain convinced that a subsequently designed biomarker-guided trial will display Cabo efficacy with a survival benefit to boot.
    Just a matter of time and patience...

  • $$$$
    Dr Kurt Miller, Chief Urologist Ben Franklin Medical Center, Berlin Germany
    Available at ecancerdotorg. Published 5/12/14. I think this lecture actually took place at the Asia-Pacific Prostate Cancer Conference last March. Good presentation. Dr Miller has published and co-authored extensively on Cabozantinib. My suspicion is that he expects approval. JMO

EXEL
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