While all cancers display uninterrupted cell proliferation, their heterogeneity often makes them difficult to treat. Given these characteristics, Plexxikon is pursuing a number of drug targets for the treatment of different cancers.

Melanoma and Colorectal Cancer

PLX4032 is Plexxikon's lead program in its expanding oncology franchise. This drug candidate is a novel, oral and highly selective drug that targets the cancer-causing BRAF mutation, occurring in about 50 percent of melanomas, 10 percent of colorectal cancers and overall, eight percent of all solid tumors. A pivotal Phase 2 clinical trial for the treatment of metastatic melanoma began in September 2009, and a Phase 3  trial began in December 2009. PLX4032 (RG7204) is being co-developed with Plexxikon's partner, Roche.

Data from a Phase 1 extension study of PLX4032 in metastatic melanoma patients with the mutation showed tumor shrinkage in nearly all evaluable patients, reflecting a 70 percent response rate. These results confirmed the preliminary safety and efficacy results seen in the previous Phase 1 dose-escalation study. In addition to melanoma, Plexxikon is also conducting a Phase 1 extension study of PLX4032 in mutation-positive patients with colorectal cancer.

Osteolytic Metastatic Disease

Plexxikon has developed a portfolio of novel drug candidates designed to treat diseases primarily driven by osteoclasts, macrophages and mast cells. These immune system cell types drive certain cancers and inflammatory diseases.

Plexxikon has initiated a Phase 1 clinical trial with PLX3397 to test the initial safety, tolerability and pharmacokinetics in cancer patients. PLX3397 is a highly selective kinase inhibitor that down-modulates macrophages, osteoclasts and mast cells, as well as certain tumor cells that promote tumor growth and metastases to the bone. A follow-on Phase 1b study is planned in patients with rheumatoid arthritis.

Preclinical data have shown PLX3397’s antitumor effects, including a decrease in circulating tumor burden, delay of tumor metastases and inhibition of tumor growth. Pending completion of the Phase 1 studies, the company is planning to explore PLX3397 in metastatic breast and prostate cancers, gastrointestinal stromal tumors (GIST), melanoma and brain cancer.