Study Treatment and Procedures
loose stools, Tumor, diarrhea, toxicity, abdominal cramping, Toxicity, skin toxicity
DISEASE PROGRESSION, SKIN TOXICITY, ADVERSE EVENT, TUMOR
In phase Ib, patients received a starting dose of binimetinib 45 mg twice daily (BID) + panitumumab 6 mg/kg once every 2 weeks (Q2W), the US Food and Drug Administration approved doses of both agents at the time. Dose de-escalation was planned as needed until the MTD/recommended phase II dose (RP2D) was reached. In phase II, patients received the MTD/RP2D of binimetinib + panitumumab, as determined during phase Ib.Tumor response was evaluated locally by the investigator according to RECIST 1.1, using computed tomography scans and/or magnetic resonance imaging with intravenous contrast. Scans were performed at screening/baseline and then every 8 weeks (two 28-day cycles) until disease progression. Safety was assessed throughout the study, and AEs were coded using Medical Dictionary for Regulatory Activities version 18.1 terminology. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 4.03. Per protocol, antidiarrheal medication was recommended at the first sign of abdominal cramping, loose stools, or overt diarrhea; skin toxicity prophylaxis was to be initiated 24 hours prior to first treatment with binimetinib or later as needed. Patients continued treatment until disease progression, development of unacceptable toxicity, or withdrawal of informed consent.