The share price of Exelixis ($EXEL) is starting a run-up (after months in the doldrums) in advance of anticipated results from the COMET-1 phase 3 trial in metastatic castrate resistant prostate cancer (mCRPC) for cabozantinib (Cometriq, formerly XL184).
Cabozantinib is a small molecule tyrosine kinase inhibitor of c-Met and VEGFR2. It has been shown to significantly improve bone scans and decrease pain, but the $64,000 questions are will patients taking it live longer and feel better?
The answers will come from the COMET-1 trial that has a primary end point of overall survival (OS). It’s a placebo-controlled trial of 960 men with advanced prostate cancer randomly assigned to cabozantinib 60mg (n=640) or prednisone (5mg twice daily) (NCT01605227) who have disease progression after treatment with docetaxel chemotherapy and abiraterone (Zytiga) or enzalutamide (Xtandi).
Subscribers to premium content can login to read my analysis as to why I thought this trial would be negative.
Update Sep 1, 2014 COMET-1 is a failure
We normally put updates at the end of a post, but we’ve just heard the trial a failure, so I think it’s appropriate to put this upfront. Am glad that our analysis turned out to be correct. Congratulations to those blog subscribers who on the basis of this post sold all or part of their $EXEL position. Commiserations if you held on.
The recent AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics international conference in San Francisco was an informative meeting.
What I particularly liked was the strategic overview that took place in many of the plenary sessions.
As an example, Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research/The Royal Marsden in London highlighted the potential drug development targets based on prostate cancer biology:
- Androgen Receptor (AR)
- Heat Shock Proteins (Hsp)
- Signaling: HER3, MET, IGF-1R, CCL2, IL-6, Src
- PI3K/AKT/TOR signaling
- PARP and BRCAness
- Estrogen receptor (ER)
- c-MYC & CHK1
His presentation discussed the possible therapeutic approaches, and complexity involved in developing novel targeted therapies for prostate cancer.
This is something that I expect we will hear more of at the AACR special conference on Advances in Prostate Cancer Research early next year.
In particular, de Bono discussed drug development strategies to target androgen receptor signaling, and some of the future challenges including:
- Proving to the regulatory authorities that circulating tumor cell (CTC) count falls are a robust immediate endpoint of overall survival
- Developing improved imaging for bone metastases
As a side note, there were several posters for cabozantinib (XL184) at the meeting (available on the Exelixis website), including preliminary research on computer-aided quantitative bone scan assessment.
However, as de Bono mentioned in his presentation, “diffusion weighted MRI shows hot spots not detected by bone scans.”
2010 and 2011 were good years for prostate cancer drugs, and with new approvals for MDV3100 and radium-223 (Alpharadin) expected, 2012 is set to be another “grand cru” year, to paraphase Bertrand Tombal.
If you were not able to make it to San Francisco for the Molecular Targets and Cancer Therapeutics conference, webcasts of many sessions will be available on the AACR site.