In conclusion, the findings of the present phase I study of TAK-733 have demonstrated a safety profile, pharmacodynamic effects, and antitumor activity consistent with other MEK1/2 inhibitors, with key toxicities including dermatitis acneiform, diarrhea, increased blood CPK, fatigue, and stomatitis, and limited single-agent antitumor activity, including a partial response in a patient with BRAF-mutant melanoma. Here, MAP2K1 is linked to melanoma.