A phase Ib/II, multicenter, open-label, dose escalation study of LGX818 in combination with MEK162 in adult patients with BRAF V600 â?? dependent advanced solid tumors
This is a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the MTD(s) and/or RP2D (s) for the combination of LGX818 and MEK162, followed by a Phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous schedule. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. Continued treatment beyond progression of disease will be allowed under certain circumstances. A cycle is defined as 28 days. Hopkins is participating in the phase II portion only.
Patient who have colorectal cancer that has spread, can not be surgically removed and for whom no standard therapy is available or patients with locally advanced melanoma or melanoma that has spread and has a specific gene alteration (BRAFV600E mutation).
Following MTD/RP2D declaration (phase Ib), patients will be enrolled in two three Phase II arms. Phase II arm 1 will consist of 28 patients with non-resectable advanced BRAF V600 mutant mCRC for whom no further effective standard therapy is available. The Phase II arm 2 will consist of 41 patients with locally advanced or metastatic BRAF V600 mutant melanoma who have progressed after previous treatment with a selective BRAF inhibitor. The Phase II arm 3 will consist of 40 patients with locally advanced or metastatic BRAF V600 mutant melanoma who are naÃ¯ve to previous treatment with a selective BRAF inhibitor. All patients will be followed for 30 days for safety assessments after study drugs discontinuation. Patients enrolled in the Phase II part of the study who discontinue study treatment for any reason other than disease progression will be followed up for progression of disease. All patients enrolled in the Phase II part of the study will be followed for survival. Johns Hopkins is participating in the Phase II part only.
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