Melanoma: FDA/Regulatory News and Trials Terminated

Updates on dabrafenib, trametinib, lambrolizumab, and more.


Merck’s PD-1 inhibitor, lambrolizumab, received “Breakthrough Therapy” status from the FDA based on trial data for this experimental antibody—a category that may enable expedited development.3

Unfortunately, in 2011, the phase III AGENDA trial revealed disappointing data, demonstrating that Genta’s “Genasense” was not significantly superior compared with patients treated with chemotherapy alone.4


In conclusion, metastatic melanoma remains one of the most therapeutically challenging malignancies, and curative treatments remain elusive. However, for the first time in decades, new drugs have resulted in significant clinical responses. Advances in basic and clinical research have produced novel treatment strategies that target specific molecules and pathways expressed in cancer cells. One of the major focuses in melanoma therapy continues to be the understanding and targeting of signal transduction pathways responsible for the tumor’s capacity for growth and resistance to chemotherapy.5Additionally, the molecular heterogeneity of melanoma, and the recognition of numerous mechanisms of resistance to targeted therapies, support the use of a combinatorial approach to treatment. Clinical management of melanoma is therefore improving with increased understanding of the molecular pathogenesis of the tumor.6

  1. FDA. Darafenib. 2013. Available at: Accessed June 16, 2013.
  2. FDA. Trametinib. 2013. Available at: http://www. Drugs/ucm354478.htm. Accessed June 16, 2013.
  3. Merck Newsroom. 2013. Available at: http:// and-development-news/merck-announces- breakthrough-therapy-designation-lambrol. Accessed June 16, 2013.
  4. Phase 3 trial of Genasense in advanced melanoma does not show significant increase in overall survival. Available at: http:// advanced-melanoma-does-not-showsignificant- increase-overall-survival-11831.html. Accessed June 16, 2013.
  5. Nikolaou VA, Stratigos AJ, Flaherty KT, et al. Melanoma: new insights and new therapies.J Invest Derm. 2012;132:854-863.
  6. Kwong LN, Davies MA. Targeted therapy for melanoma: rational combinatorial approaches.Oncogene. 2013;1-9.