I see no importance to the timeline. I figure a collaboration like this one is solely directed toward placing a compatibility value on Cabo in combination with Roche's existing onco-arsenal. Since Herceptin has become an SQ injectable, compatibility with Cabo would be viewed as a marriage of convenience. An additional small Genentech-sponsored trial or two wouldn't surprise me...if there is unexplored commercial value in Cabo, Roche will find it.
"...more than doubles survival in some pancreatic tumor models."
It could be the presentation will give us some direction wrt the recent CDX IP patent filing. Doubling survival is no doubt a great feat, but predicting the patient group that will realize that benefit is potentially a huge play in trial population enrichment.
"What is the new IP worth?
For now...priceless. With competent CDX, everyone benefits. Docs, institutions, patients, payors, shareholders...everyone. Identifying high response patient groups is the stuff of the future, and I am thrilled to see HALO has recognized the importance of targeting specific patient subsets. This cannot be overstated...
Trial designs of the future will reflect the competence of the IP...
I suspect that one of Mr Market's observations that is sitting on the SP is the prospective tenure that V&C may enjoy in the advanced melanoma treatment algorithm. By far the preponderance of superior data is coming from the checkpoint inhibitors, and I think market perception remains focused on the perception that Cobi will enjoy but brief adoption, and eventually be replaced by a CI with a more moderate AE spectrum.
At any rate, I'd be prepared to see PDi displace TT in adv melanoma. Nivolumab isn't the one, but it's out there... Hopefully, Cobi is compatible, synergystic, and economical.
Posted in today's JCO. JMO - but I suspect BRAF monotherapy in advanced melanoma just became a thing of the past, so we might actually see an expedited review for Cobi...
"Conclusion Dabrafenib plus trametinib has modest clinical efficacy in patients with BRAF inhibitor–resistant melanoma. This regimen may be a therapeutic strategy for patients who previously benefited from BRAF inhibitor monotherapy ≥ 6 months but demonstrates minimal efficacy after rapid progression with BRAF inhibitor therapy."
The balance of future use if Cobi still lies in the comparative AE profile. Stay tuned...
Dr Paul Corn has published extensively on Cabo in prostate analysis, and it's good to see he still appears to be on board in the wake of Comet's failed OS signal. A strong showing in a Comet -2 could provide the NCI / IST funding for a VDA/chemo/ Cabo designed study such as these authors have suggested.
Looks like another semanresu/ Offsitehelp alias to me...
2 posts | Last Activity: 5 minutes ago
Member since: Sep 26, 2014"
Two thumbs down within a half hour...it's great to feel welcome.
Another interesting note here, PCF SR14 abstract submissions have been extended to 10/7/14, making this a possible venue for further prostate results, perhaps including additional readout on Comet-1.
Now, y'all can put those thumbs where they truly belong...
Amongst the interesting prostate-related studies being presented, I found this:
"C-Met and the emergence of resistance to potent androgen suppression" Morgan, et al...
Using bortezomib to sensitive cMET accumulation to XL-184 inhibition in AR axis manipulation in PCa...
Another with mention of Cabo:
"Crizotinib and enzalutamide before and after progression on docetaxel" Harshman, et al...
"...things are not as bleak as indicated by current share price..."
Awwww geez, Joe...ya go and bring a bit o' sensibility to the YMB and yer sure to incur the wrath of semanresu Ph.d (which, in case you didn't know, stands for PHairy dust)...
...and all his aliases - play dirt, play dough, miracle gro, and cheez whiz...
We're screwed now...
In addition, Roche is conducting combo trials utilizing ARRY's MEK-162...and these will bear watching for any progress favoring ARRY MEKi product over Cobi - or vice versa...
Best case in point for expanding the use of Cobi/Vemurafenib that I can find is in melanoma with active brain metastasis. Roche has a maturing P2 in V monotherapy(active, not recruiting), a P2 in combination with radiotherapy (not yet recruiting), and the most recent combo with Cobi (not yet recruiting) on their plate. There is also a recent PGlycoP brain barrier crossover study for Cobi that bodes well for this combination, and I am optimistic to see where Roche goes with this bolt-on indication...
It may also prove of value to track the direction of the existing Novartis D&T combo... Both BP's will pick up the development pace if only for first-mover status, and Cobi could easily enjoy the coattail ride of rapid V program expansion...
"The market is asleep at the wheel on HALO..."
Though the lack of gainful volume is a bit surprising, the recent insider buys were good reinforcement of your thesis. "Asleep at the Wheel" is one of my all-time favorite bands...
Xalkori priced monthly - $12,113
Inlyta priced monthly - $10, 313
Perhaps Cabo is not priced high enough...???
"What are your thoughts on Comet 2 results as far as adding to share value?"
Check out the new thread I posted on MET VEGFR bone effect accomplished by combined Axitinib/ Crizotinib therapy. This is obviously a Pfizer- sponsored study, but it at least confirms that the Cabo effect is not a misread of imaging uptake, an illusion, or a biased research agenda. The effect is apparently real, as are the benefits of fewer bone lesions, improved pain response, and normalized bone remodeling. Truly robust Comet-2 results could conceivably create an sNDA filing scenario for Cabo, but there would almost certainly be the controversy of lacking statsig survival to argue. The palliative and hospice communities might muster a suitable lobby if it were to go to ADCOM. The science is still evolving, and the continued positivity in reporting is a very good sign. We'll simply have to wait and see...
"Axitinib and crizotinib combination therapy inhibits bone loss in a mouse model of castration resistant prostate cancer." BMC Cancer 10/2/14 Eswaraka J, et al...
Here's what the company website has to say wrt it's P3 trials:
"Ongoing Exelixis-sponsored global, randomized phase 3 pivotal trials of cabozantinib include the METEOR study in metastatic renal cell cancer and the CELESTIAL study in advanced hepatocellular cancer.
We are also continuing to follow patients enrolled in COMET-2, our phase 3 trial of cabozantinib in metastatic castration-resistant prostate cancer (CRPC), and we anticipate data from that study before the end of 2014. We also anticipate results from the overall survival analysis of EXAM, our phase 3 trial in metastatic medullary thyroid carcinoma, by year-end."
How do these words downplay any of their efforts or any future results? Further, the P4 study in MTC is not something EXEL "says they want to do"... That study was an FDA condition of MTC approval: a postmarket follow-up to further assess risk, benefit, and dosing. What leads you to believe EXEL simply wants to conduct another trial? You are drawing a continued picture of a CEO cruising down Highway 101 in a Caddy convertible - tossing $100 bills into the wind...Why?
See the company PR dated 9/2/14. That announcement states that cabozantinib efforts in CRPC have been de-prioritized, and recruitment in Comet-2 has been halted, along with all other EXEL-sponsored trials in the prostate space. There is still a high likelihood that Comet-2 enrollment numbers are high enough to validate the statistical powering of that trial, and the primary endpoint - pain relief noted at week 6 durable thru week 12 - may yet read out later this year. By trial design, data lock will occur 12 weeks after the final patient was dosed - so we're looking at 12/1/14 at the very latest...the actual timeframe is likely somewhat sooner. The company may want to explore the regulatory pathway in CRPC at that time (which I doubt) but my opinion is that we may not see timely Comet-2 results unless they are very, very favorable. Personally, I'll be disappointed if we don't see a regulatory filing based upon pain palliation, improved HrQOLs and increased patient function. I'd enjoy the high drama of an ADCOM review, and would like to hear the expert commentary from both sides of the Cabo debate.
Early in the data-gathering process - and concurrent with the P1b Vilnius EADO results that were announced last Spring, Dr Peter Lamb made commentary wrt DHCP letters being sent out globally. This concurs with your thoughts on an expeditious review process. The Novartis (ne GSK) combo D&T -already approved in the US - may constitute a barrier to perceived unmet need in the States. In Europe, I feel an expedited review may be a shoe-in. One way or the other, we should know by year's end. JMO - but I feel Roche will press their strongest suit on home turf, and let the "bloody yanks" figure it out as they must...
Personally, I feel D&T covers the immediate need for a BRAF/MEK doublet in advanced melanoma, and I don't expect an expedited review Stateside.