"The question is what exel will do if it succeeds in pain and bone responses?
What if OS is statsig in COMET-2?"
Controversy, debate, and expert testimony possibly resulting in ADCOM.
Everybody have a great holiday!
"...does EXEL get any payment from Merck ?"
If they do, it'd be a pretty neat trick.
In developing cobimetinib, EXEL is partnered with Roche...
Initial documentation of patient progress via application of the Abbreviated Injury Scale should take place on or about 1/15/15, and each 3 months thereafter. Without an associated comparator, I'd expect expert analysis of clinical perception to determine treatment viability. Even if the news proves great for Jarrod, I wouldn't expect much real information to be released pending presentation at a future neurologic venue. Clinical protocol and patient privacy rights will take priority over shareholders in the near term. Patience will be required with these early interventions as trial protocols may need be amended, and peer review of trial analytics will be an important factor in determining the most appropriate pathway forward. GLTA
I wanna be Martini...and if you say I can't...
I'm done. Puh-leeze lemme be the Man...
"So, are you proposing the secondary endpoints of Comet-1 and Comet-2 could qualify for a PIII?"
Not at all...but I am suggesting that the aggregate of all mCRPC data will adequately define a Cabo-sensitive patient group that will inform a trial designed toward validating Cabo's efficacy within a defined subset. Duckduffer had mentioned this in an earlier post, and he and I are in agreement that a likely target population might be the one which responds well in the initial 12 weeks of Cabo therapy, utilizing therapeutic response to Cabo in terms of optimum BSR, concurrent pain relief, CTC reduction greater than 50%, bone turnover markers, and therapeutically responsive hemoglobin and LDH levels.
Differentiating the responsive group from the non-responsive group would be key to determining EXACTLY which patients constitute your target group for Cabo. "High grade" the patient pool - so to speak...
Easier said than done, but such patient definition would inform a trial virtually guaranteed to succeed, albeit in a smaller, less commercially viable patient pop... I feel this is an inevitable culmination to these lines of research - defining a trial group targeting a hazard ratio closer to .6 than .9. Statsig OS achieved based upon early response to Cabo therapy, while admitting that there will be patients that Cabo can not hope to help.
The abstract is available in entirety at the ECCOdotorgdoteu website. No biggie, as it is a Roche preclinical work up. I mention it specifically to elucidate Cobi potential beyond what is known currently. I see compatibility with ERK inhibition as very positive.
"Conclusions: The robust and dynamic nature of MAPK signaling, particularly in the context of therapeutic intervention, helps to explain the limited clinical success observed with single agent MAPK-targeting strategies tested to date. Our results elucidate a highly effective strategy that combines MEK and ERK inhibitors to more significantly suppress the MAPK pathway. These results add to the fundamental understanding of how the MAPK pathway mediates oncogenic signaling and offers a new combination approach to target MAPK dysregulated tumors."
"The one that ulingt pointed out is specifically for bone. Comet-1 and Comet-2 were neither for bone. It's a different study altogether..."
We'll have to agree to disagree here. Bone scan response and interpretation are secondary response measures in both Comet trials. As far as the UMCC P2 study being bone specific...sure, but still bone specific in mCRPC. What you are neglecting to see is that the aggregate of trial analysis is attempting to tie BSR, pain relief, and biomarker assay to reliably predictive OS. Biomarker guidance will prove key to any future success for Cabo in mCRPC , or - IMO - it will become another missed opportunity, subject to the prescription whims of evidence-based oncology, as opposed to becoming part of the SOC treatment algorithm.
Ulingt, my apologies for the earlier incomplete response. I got distracted. I hope you had the opportunity to check out the Dave Smith UMCC abstract. There's a lot of good info there, and I suspect secondary outcome reporting will be favorable as well. MMM has said many times that the regulatory path forward is unclear for Cabo in mCRPC, and also that the aggregate of evidence from the Comet trials will be critical to determining the future use of Cabo in that indication. No one knows (not even semanresu) how that will play out, but let me suggest this to you for your consideration:
Cabo has displayed a clear, undeniable history of therapeutic benefit in managing mCRPC. Whatever the reason for Comet-1 failure to display statsig OS, the resultant survival benefit still favored the Cabo treatment arm in that trial (HR less than "1"). Despite favorable primary endpoint results from the UMCC P2 trial, I don't expect another such relevant P3 trial will be pursued. Rather, I expect that the mature Comet data will be pooled and screened for clues to identify Cabo's most responsive patient group. All the biomarker data being generated by the CRADA/CTEP/NCI/IST partnerings will be utilized to this end...including SU2C, PCF, and patient-generated data wrt hrQOL related benefit. JMO, but no clearly-defined Cabo-sensitive patient group = no regulatory path forward in mCRPC. The aggregate of peer-reviewed data will be fully utilized, and no stone will be left unturned. That said, I don't expect to see an sNDA filing for Cabo in mCRPC anytime soon - regardless of Comet-2 results. If the aggregate of data remains favorable, I DO expect to see the NCCN make some future determinations of Cabo use in the prostate space based upon ongoing clinical perception, clear evidence of benefit, and the emergence of a biomarker-defined Cabo sensitive patient population.
This study met its primary endpoint and published (minus presentation at ASCO 2014.
2014 ASCO Annual Meeting I encourage you to visit it in the ASCO library.
Just a heads up...this EORTC data will be presented tomorrow - 11/20...
Notably, the Roche PDL-1 melanome trial in combo with V&C has been updated this month, and two 7-patient expansion cohorts have been added to revise scheduling and sequencing of the PDL-1 Ab component. If I've read the revision correctly, Vemurafenib and cobimetinib dosing is being maintained to similar levels of the initial trial design. Two years into this trial, and they've decided to add patients. Hmmmmm...
In addition, there is a "Trials in Progress" presentation on Celestial (HCC) by Abu-Alfa - another half-witted witch doctor pumping voodoo medicine... Oh well...
I know...I know...it's probably just another poorly designed trial being conducted by a trove of incompetents... generating a bunch of absolutely trivial, totally meaningless data. But -what the heck, ol' Seymour needs to have something to gripe about, doesn't he?
A Phase II trial of Cabozantinib (XL-184) in Patients with Advanced Cholangiocarcinoma. (Abstract 800)
Presenting Author: Lipika Goyal
Just a heads-up. According to Table 2 in "New developments in the treatment of metastatic melanoma – role of dabrafenib–trametinib combination therapy" JJ Luke et al DovePress 6/2014... Dana Farber Cancer Institute is planning a Phase 1/2 trial of Vemurafenib, cobimetinib, and SNTA's HSP90 inhibitor, ganetespib, in metastatic melanoma. No timeline is given, but this trial may lend some comparative insights as to what we might expect to see in the proposed Moffitt trial planned for EXEL's HSP90i in what should be a very similar cocktail. Interesting times ahead, and these trial comparisons may set the baseline for the overall commercial viability of XL-888, particularly as ganetespib has the near-term strategic advantage of several P3 trials already in progress across a variety of indications. It's a sure bet lot of clinicians will be paying close attention as these trials progress, as will investors in both EXEL and SNTA...
"You obviously haven't been on this board for too long."
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Member since: Oct 10, 2014
Additionally, there are two noteworthy additions to the NCCN ORP Steering Committee:
Razelle Kurzrock of UCSD Moores CC, and Dave Smith of UMich Comp CC...
Both have published extensively on Cabozantinib...particularly Ms Kurzrock...
Whose research is notably intertwined with the clinical progress of Cabo...
Interesting survey. I mention it because of the third question in line behind treating EGFR and ALK driven disease - and, remarkably - this survey reveals that very few oncodocs are performing IHC testing in this indication for MET amplification, although MET is amongst the top suspects in progressive disease. Good breakdowns on drug utility in an IHC-driven treatment regime, and good rationale for the Tarceva/Cabo combo rationale. Worthwhile read...available free at NCCNdotorg.
"What are you growing..."
For now, veggies... I've still got tomatoes ripening on the vine.
But in retirement, the cash crop will be pharmaceutical weed.
I'm simply a chronic tinker - what I call a tinkerholic. I'm just putting the finishing touches on a solar air heater for my greenhouse. I chose the "screen" collector design for ease of construction and future maintenance/parts replacement. The 4 x 6ft collector box is powered by a 12v solar-powered fan that moves 50cfm in direct sunlight. I just tested for delivery-efficiency today, and at OAT 63F the unit was blasting a steady state volume at nearly 170F with inlet filter uninstalled. Surprising efficiency, and pretty darn reasonable cost-wise (
Yup, and Edison didn't invent a gazillion incandescent light bulbs...
He started with a few...
Great achievement begins small...
92% ORR. 12% CRs. Great potential here...
Then the wet blanket shows up...
No one will care much about zero shareholder equity...
When EXEL has a bazillion dollar market cap...