Exelixis, Inc. (Nasdaq: EXEL) is reporting the expansion by Roche (OTCBB: RHHBY) and Genentech, Exelixis’ collaborator and a member of the Roche Group, of the clinical development program for the MEK inhibitor cobimetinib (GDC-0973/XL518). As disclosed on ClinicalTrials.gov, Roche and Genentech are initiating the following new clinical trials of cobimetinib in combination with other agents:
* A Phase 1b, Open-Label, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of MEHD7945A and Cobimetinib in Patients with Locally Advanced or Metastatic Solid Tumors with Mutant KRAS (NCT01986166);
* A Phase 1b, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Onartuzumab in Combination with Vemurafenib and/or Cobimetinib in Patients with Advanced Solid Malignancies (NCT01974258); and
* A Phase 1b Study of the Safety and Pharmacology of MPDL3280A Administered with Cobimetinib in Patients with Locally Advanced or Metastatic Solid Tumors (NCT01988896).
These new phase 1b clinical trials are being conducted by Roche and Genentech under Exelixis’ worldwide co-development agreement with Genentech and are being initiated on the basis of a strong scientific rationale and encouraging preclinical data.
MEHD7945A is a dual specificity antibody targeting EGFR and HER3. Mutation of KRAS and subsequent activation of the MAP kinase pathway independent of EGFR/HER3 may limit the efficacy of agents such as MEHD7945A in KRAS mutant tumors. Co-administration of a MAP kinase inhibitor such as cobimetinib to block signaling downstream of KRAS is therefore a rational combination approach to the treatment of KRAS mutant tumors.
Onartuzumab is an antibody directed against the receptor tyrosine kinase MET. Activation of MET by its ligand HGF limits the response to agents such as vemurafenib (as published by Straussman et. al. in Nature, Volume 487 (19 July 2012), page 500, and Wilson et. al., in Nature, Volume 487 (19 July 2012), page 505), and co
So many spin artists. This is good news and not to be rationalized. They would not spend the money if potential not very large and success deemed probable. That is the bottom line. I put faith in these very highly credible endorsements, over anything said here. The core positions just got further endorsement. My target for next year remains at dollar twelve plus.EOS
Nice to see more studies of Cobimetinib are taking place.But this one is just beginning.
"Estimated Enrollment: 96
Study Start Date: November 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)"
From my Nov.4th post Cobimetinib: A compelling reason why the Cobimetinib Roche-Genentech/Exel collaboration is so positive. It's sure an Ace in the hole for Exel.It can add money to the Exel coffers. And give further proof of Exel's competence.The money and power of Roche a proven company.Hoffmann-La Roche AG, Basel, Switzerland,one of the largest pharmaceutical companies in the world. Roche-Genentech just confirmed guidance on their recent Q3 earnings call that they expect to have top line data and pursue regulatory filings for cobimetinib from the coBRIM study in 2014 as well.
A little confused here (some may say that I am more than a little confused); if cobimetinib (GDC-0973) is being tested as an adjunct to vemurafenib (Zelboraf) why is Roche bothering with onartuzumab , which is only a one-armed monoclonal antibody (inhibiting cMet only), as opposed to cabozantinib which inhibits more than just cMet? Wouldn't cabo be more appropriate since it blocks or inhibits more than just cMet?
I'm not sure if I even phrased the question correctly but I hope some of the more medically knowledgeable posters can shed some light.
Sentiment: Strong Buy
In addition, Haura & Smith of Moffitt CC just published in the JCO (Nov 10) on concurrent MET/EGFR inhibitor rationale in lung cancer with solid OS results in a high-MET subset group treated with Onartuzumab. Could be Roche sees low-hanging fruit...