Ridaforolimus (MK-8669), under evaluation by Merck and Ariad Pharmaceuticals, blocks cancer cell growth and proliferation by inhibiting the mammalian target of rapamycin (mTOR). A phase III clinical trial with oral ridaforolimus was recently completed in patients with metastatic soft-tissue and bone sarcoma that responded favorably to chemotherapy. Ridaforolimus in various phase I and II clinical trials as monotherapy in non-small lung cancer expressing mutant Kras, and endometrial cancer and in combination with other targeted therapeutics, including trastuzumab in breast cancer and MK-0646 in solid tumors. Merck has undertaken a biomarker research program to design rational combinations with deforolimus, identify responder profiles, and inform decisions in alignment with the clinical trial program.

Roche submitted a Biologics License Application (BLA) to the FDA for trastuzumab-DM1 (T-DM1) in patients with advanced HEr2-positive breast cancer previously treated with multiple HEr2-targeted therapies. This submission is based on the results of a phase II clinical trial (protocol ID: TDM4374g; NCT00679211) in which T-DM1 shrank tumors in one-third of women who had been previously treated on average with 7 separate regimens for advanced HEr2-positive breast cancer. T-DM1 is the first of numerous antibody-drug conjugates (ADC) in development to be submitted to the FDA for approval. Roche itself is investigating 50 separate ADC constructs in a variety of malignancies.

In October 2009, Arzerra (ofatumumab) received accelerated approval from the FDA for use in patients with chronic lymphocytic leukemia (CLL) that is refractory to treatment with fludarabine and alemtuzumab. The drug is being commercialized by GlaxoSmithKline under a global license from Genmab. Arzerra is a monoclonal antibody (MAb) that attaches to the small and large loop epitopes on CD20 found on the surface of B-cells, and recruits the body's natural defenses to attack and kill these selected cells that are implicated in cancer, and autoimmune and inflammatory diseases. Arzerra is one of several approaches currently in development for the treatment of CLL, an incurable hematologic malignancy (see http://www.ncbi.nlm.nih.gov/pubmed/19619273?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=9). Arzerra is in development for other indications, mostly in combination with other approved agents.

Azatoxin, a hybrid of etoposide and ellipticine, originally proposed in the early 1990s, is back in the news as a more favorable cytotoxic alternative acting as a topoisomerase II inhibitor and a spindle poison. Certain azatoxin derivatives are 100 times more active than etoposide.
http://www.thefederalregister.com/d.p/2009-04-23-E9-9344