Saturday at the 2012 meeting of the American Society of Clinical Oncology (ASCO) I was able to look at the following very interesting therapeutics which are novel treatments that primarily target tumor escape pathways. These include:
Cabozantinib (XL-184) from Exelixis (EXEL): Cabozantinib (XL184) is an oral, potent tyrosine kinase inhibitor of MET, VEGFR2, and RET that is currently undergoing evaluation in several oncology indications such as Breast Cancer Gastrointestinal (Non-colorectal) Cancer, Genitourinary Cancer, Head and Neck Cancer, Lung Cancer - Non-small Cell Metastatic, Melanoma/Skin Cancers. What is important about this drug is that it appears to show preliminary evidence of use where VEGFR inhibitors fail (targeting escape pathway). One aspect of the drug is that it seems highly effective at preventing bone metastasis. This could very well be a niche market and Exelixis is pushing hard to develop multiple indications for the drug.
Anti-PD-1 (BMS-936558, MDX-1106) from Bristol-Myers Squibb Co (BMY): Much has been learned in the last two decades regarding how the immune repose to cancer is regulated. For example we have learned that there are positive and negative signal pathways that regulate T-cells. One of the most important negative signaling pathways is the interaction between programmed death-1 (PD-1) receptor on T-Cells and the PD ligand-1 (PDL-L1) on antigen presenting cells. This immune checkpoint suppresses activated T-Cells and promotes tolerance. PDL-L1 can be expressed on tumor cells as part of a process known as adaptive immune response. Over expression of PDL-1 is correlated with more aggressive disease and shorter survival. The blocking of the PDL-1 with a monoclonal antibody allows T-Cell priming and prevents tumor induced T-Cell suppression and this was much of the focus of the studies featured at the meeting. Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) was presented in patients with previously treated metastatic renal cell carcinoma (mRCC), in addition to 9 other presentations were featured overall. The main point, other than successful tolerability and efficacy in Ph I and II trials, is that there was a demonstration of the importance of the PD-1/PD-L1 pathway for cancer immunotherapy and there is strong support for further clinical development of anti-PD-1/PD-L1 directed therapy. The studies also showed that the patients not expressing PD-L1 do not respond to the drug which means that patient selection criteria can likely improve the study results. In my estimation this is a very important drug that investors should keep their eye on as targeting the immune suppressing activity of tumors is truly an unmet need.