E6201 shows potential in treatment of advanced solid malignancies
A phase I study of E6201 has shown the feasibility and safety of an intermittent regimen of 320 mg/m2 by intravenous (IV) infusion once-weekly (qw) for the first 3 weeks of a 28-day cycle in patients with advanced solid malignancies, including melanoma.
“Additionally, we show preliminary evidence of clinical efficacy, confirming the potential of MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase) inhibition and selective MEK1 inhibition, as a therapeutic strategy in cancer,” the investigators said.
In part A of the study (dose escalation), sequential cohorts received E6201 IV over 30 min qw (days [D]1 + 8 + 15 of a 28-day cycle), starting at 20 mg/m2, increasing to 720 mg/m2 or the maximum tolerated dose (MTD). In part B (expansion), patients with B-type Raf (BRAF)-mutated or wild-type (WT) melanoma received E6201 320 mg/m2 IV over 60 minutes qw (D1 + 8 + 15 of a 28-day cycle) or 160 mg/m2 IV twice-weekly (D1 + 8 + 15 + 18 of a 28-day cycle; BRAF-mutated only).
MTD was 320 mg/m2 qw in part A (n=25) and confirmed in part B (n=30). QT prolongation (n=4) and eye disorders (n=3) were some of the reported adverse events.
There was a dose-related exposure of E6201, with pharmacokinetics characterized by extensive distribution and fast elimination. Partial response was reported in one patient during part A (BRAF-mutated papillary thyroid cancer; 480 mg/m2 qw) and in three during part B (2 BRAF-mutated melanoma; 1 BRAF-WT melanoma; all receiving 320 mg/m2 qw).
“E6201 is being further investigated in a phase I/II trial in patients with advanced haematologic malignancies with the FLT3 mutation,” the investigators said.