Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘MET’

This morning, I woke up early to a sad announcement from Genentech that:

“The Phase III METLung study of onartuzumab (MetMab) in combination with Tarceva in MET-positive, advanced non-small cell lung cancer did not meet its primary endpoint of overall survival in a planned interim analysis. At the recommendation of an independent data monitoring committee, we are voluntarily terminating the trial. Adverse events were similar between the two arms.”

Although the full data isn’t yet available, it will be presented at a future medical conference. My guess is that ESMO in Madrid will be a possibility, if the ASCO deadline has already passed.  I’ve been avidly following the concept of MET inhibition in advanced lung cancer for both ArQule’s tivantinib and Genentech’s MetMab (onartuzumab) since the data was first presented at ESMO nearly four years ago.  These posts are still available on Pharma Strategy Blog (open access).

To read my thoughts and analysis on the results of this important trial, subscribers can sign in or sign up in the box below.

It’s hard to believe that the countdown to the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) is now underway, but yesterday at 6pm, the ASCO abstracts were released.

Oliver Sartor at the recent annual meeting of the American Urological Association (AUA) highlighted the prostate cancer potential of cabozantinib (XL184), an oral inhibitor of MET and VEGF kinases, so it was interesting to see that new data will be presented at ASCO.

What makes cabozantinib interesting?

The preliminary data shows that it not only has an anti-tumor effect, but also has an effect on bone metabolism.

The data presented at EORTC last year and at ASCO GU this year confirms what was seen in animal models, in that it had both an anti-metastatic effect on soft tissue and blockade of bone lesions.  Such dual action on both bone mets and the tumor microenvironment makes it an exciting new compound in prostate cancer.

By all accounts, the novel effect of cabozantinib on bone mets is unexpected.

At the forthcoming ASCO meeting, abstract 3010, whose lead author is Dr Michael Gordon of Pinnacle Oncology Hematology in Scottsdale, AZ  will present data on:

“Activity of cabozantinib (XL184) in soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors.”

According to Dr Gordon in the ASCO press teleconference yesterday, the phase II data at ASCO for cabozantinib in prostate cancer will show:

Complete or partial bone scan resolution in majority of patients (86%), often accompanied by pain relief

Unprecedented bone scan improvement

On the basis of these promising results, according to Dr Gordon, “Exelixis plans to initiate the first pivotal trial in prostate cancer by the end of 2011.

It will be interesting to see whether cabozantinib can impact overall survival (OS) in advanced prostate cancer, something that denosumab (Xgeva®) failed to show in the 147 trial that was just presented at AUA.

There are several abstracts on cabozantinib at the ASCO 2011 annual meeting. Another one that caught my attention was abstract 4516, whose lead author is Maha Hussein of the University of Michigan.

Dr Hussein will present data on cabozantinib in metastatic castrate resistant prostate cancer (mCRPC). The abstract’s conclusion is that:

Cabo showed clinical activity regardless of prior D in mCPRC pts, particularly in pts with bone disease, as reflected by high rates of b-scan resolution and pain relief, in addition to improvements in Hb and tumor regression.

I’ll be at ASCO in a few weeks time, so look forward to hearing more detail on the cabozantinib results.  The data is still very preliminary, but cabozantinib (XL184) is certainly a drug to watch, and may be an exciting new prostate cancer drug in the future.


There is a lot of focus at the annual meeting of the American Urological Association (AUA) here in Washington DC on metastatic castrate resistant Prostate Cancer (mCRPC), and the recently FDA approved adrenal steroid inhibitor, abiraterone acetate (Zytiga®).

Drugs in development that target the androgen receptor, such as MDV3100, are also generating a lot of interest from urologists.

However, Oliver Sartor (Tulane) in the Saturday morning satellite symposia that I attended, focused on emerging therapies in CRPC, beyond the androgen axis. His hypothesis:

“Cancers are devious and some of the mechanisms of AR activation appear to be ligand-independent and resistant to all current androgen-axis targeted therapies.”

What this means is that focusing on adrenal steroid inhibition or blocking the androgen receptor may not be sufficient to prevent disease progression. If we are looking for a Prostate Cancer cure, then will it take multiple drugs, including those that target various stromal sites? That is the intriguing question that Sartor raised.

Indeed, if there is one take home from this meeting, it is that the “desert” of prostate cancer therapies has now blossomed into a multiplicity of potential new therapies and development, which will mean that urologists and oncologists will soon be spoilt for choice as abiraterone and MDV3100 are not the end of the story.

Sartor highlighted some interesting ones on the horizon to watch out for:

Alpharadin: This is a bone targeted therapy that uses radioactive Radium 223 to kill cancer cells. It is being developed by Norwegian company, Algeta in partnership with Bayer Schering Pharma AG. The 900 patient phase III trial completed accrual earlier this year in Jan 2011. Phase II data was published in the Lancet in 2007 by Nilsson et al. Data from alpharadin will be “coming soon” according to Sartor.

XL-184 (cabozantinib): Activated MET is highly expressed in prostate bone metastases. Exelixis XL-184 is a small molecule tyrosine kinase inhibitor that specifically inhibits both MET and VEGFR2.

Data from a phase 2 study of XL-184 in castrate resistance patients was presented last year at the EORTC-AACR-NCI Symposium on Molecular Targets and Cancer Therapeutics in Berlin by David Smith et al (Abstract 406).

Both XL-184 and alpharadin would be potential competitors to Amgen’s denosumab (Xgeva®).

Other new products in development “Beyond the Androgen Axis” that Dr. Sartor mentioned included Prostvac-VF, BPX-101 and ipilimumab. A phase III trial of ipilimumab, both pre- and post- docetaxel is now underway in mCRPC. A phase III trial of Prostvac-VF will start later this year with 1200 patients in a placebo controlled study with minimally symptomatic, castration-resistant metastatic prostate cancer patients.

Over the next few years a lot of data may emerge on exciting new treatment options. Coupled with the basic research that is going on, tremendous progress in the treatment of Prostate Cancer is already taking place.

According to Sartor “multiple drugs will be necessary to cure mCRPC and that is our greatest challenge today.” Major progress is now being made towards this.

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