clinical trial drug combos for targeted therapies….

don't know about you, but a lot of these i have never heard of before…have to do my own research and thought it would be helpful to share.  i got this from the Aim website….boots

BRAF Inhibitors in Combination

There are several clinical trials looking at the combination of vemurafenib (Zelboraf) with the older and newer drugs. There will also be a trial testing dabrafenib in combination.

• Vemurafenib + Ipilimumab (brand name Yervoy) is a combination of a targeted therapy and an immunotherapy in patients with the BRAF V600 mutation.

• Vemurafenib + Bevacizumab (brand name Avastin) is a combination of a targeted therapy and an anti-angiogenic therapy.

• Vemurafenib + BKM120 combines two targeted therapies. BKM120 is a targeted agent that inhibits a molecule called phosphatidylinositol 3-kinase (PI3K).

• Dabrafenib + Trametinib combines a targeted therapy with a MEK inhibitor. The phase 2 study showed that the frequency of responses in the combination is similar to dabrafenib alone, but with the addition of trametinib these responses may be longer lasting with reduced side effects.  A study of dabrafenib plus trametinib versus dabrafenib plusplacebo is now in preparation.

MEK

MEK is a critical member of the MAPK pathway involved in growth and survival of cancer cells. 

• Trametinib is a potent and highly selective inhibitor of MEK activation and kinase activity. It is now in a phase II clinical trial to investigate the objectiveresponse rate, safety, and pharmacokinetics in patients with the BRAF V600 mutation who were previously treated with a BRAF inhibitor.  

• Selumetinib is given either as a single agent or in combination with MK-2206 (a new compound inhibiting another protein important for cancer growth called Akt). Currently the drug is being tested in melanoma patients with the BRAF V600 mutation whose disease has progressed after being treated with vemurafenib or dabrafenib.

 C-KIT

Mutations in KIT are most frequently seen in certain melanoma subtypes, particularlyacral lentiginous melanoma (melanoma of the palms, soles, and nail beds), mucosal melanomas, as well as those melanomas associated with extensive sun damage. In those patients treatment with KIT inhibitors such as imatinib and sunitinib has been reported to be beneficial. 

• Imatinib (brand name Gleevec) is approved for the treatment of chronic myeloid leukemia and Gastrointestinal Stromal Tumors (GIST). Tumor shrinkage has been reported in melanoma patients with KIT mutations and multiple Phase II trials are currently testing imatinib alone or in combination with chemotherapy for this group of patients. 

• Nilotinib (brand name Tasigna) is approved for the treatment of chronic myeloid leukemia and is currently being tested in melanoma patients with KIT mutations.

• Dasatinib (brand name Sprycel) is approved for chronic myeloid leukemia and is being tested in multiple Phase II trials for melanoma patients with KIT mutations. 

Other Targets with Potential in Melanoma

Several other pathways and targets are currently being explored in melanoma. The following is a list of some targets for which drugs are being tested in early phase clinical trials: CDK2, CDK4, and ERBB4.