Study Objectives and Endpoints
toxicities, DLTs, intercurrent illness
DISEASE PROGRESSION, ADVERSE EVENTS, DISEASE, SECONDARY, REGRESSION
The objective of phase Ib was to determine the maximum tolerated dose (MTD) of binimetinib + panitumumab. The MTD is defined as the highest combination drug dosage not causing medically unacceptable dose-limiting toxicities (DLTs) in more than 35% of treated patients in the first cycle of treatment, based on an adaptive 5-parameter Bayesian logistic regression model. DLTs were defined as adverse events (AEs) or clinically significant abnormal laboratory values assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurred within the first 28 days of treatment and met prespecified criteria. Infusion-related reactions were not considered DLTs.The primary endpoint in phase Ib was the incidence of DLTs in the first 28-day cycle of treatment (cycle 1). Secondary endpoints included frequency and severity of AEs, overall response rate (ORR) per RECIST 1.1, progression-free survival (PFS), duration of response (DOR), and disease control rate (DCR). In phase II, the primary endpoint was ORR, and secondary endpoints included frequency and severity of AEs, PFS, DOR, and DCR.AEs of special interest (AESI) were those for which there was a clinical interest related to the mechanism of action of the drug under investigation. These AESIs were defined on the basis of signals observed from previous studies in the binimetinib clinical development program and/or known class effects of other MEKi.