Clinical Data
This ongoing phase 1b trial includes both a dose escalation stage and dose expansion stage. The trial’s primary objective is the evaluation of the safety and tolerability of the combination. Secondary endpoints include objective response rate (ORR) per RECIST, duration of response, progression-free survival (PFS), overall survival (OS), as well as evaluation of biomarkers.As of the February 12, 2016 data cut-off, 23 patients with advanced CRC (22 with mutant KRAS and one with wild-type KRAS) were enrolled during the trial’s escalation and expansion phases. No dose-limiting toxicities were observed. The median follow-up for safety in CRC patients was 3.8 months, with a range of 1.1 to 15.1 months. There were no all-cause grade 5 or treatment-related grade 4 AEs reported, and incidence of treatment-related grade 3 AEs was 35% (n=8). The most common treatment-related AEs, regardless of severity, included: diarrhea (70% of patients); fatigue (52%); dermatitis acneiform (44%); rash (35%); and nausea, maculopapular rash and pruritus (each 26%).The ORR for the combination was 17%, including four confirmed partial responses; additionally five patients achieved stable disease. The median duration of response was not yet reached, with a range of 5.4 to more than 11.1 months.Median PFS for all CRC patients enrolled in the trial was 2.3 months, with a range of 1.8 to 9.5 months. The six-month PFS was 35%. Median OS for all CRC patients was not evaluable, while six-month OS was 72%.