Aim: Pmab, ril, and gan are fully human monoclonal antibodies against epidermal growth factor receptor, hepatocyte growth factor, and insulin-like growth factor receptor 1, respectively. The safety and efficacy of ril or gan with pmab in patients with WT KRAS mCRC is presented.
Methods: Part 2 of this 3-part study was a phase II, randomized, double-blinded, placebo-controlled trial of 3 arms: pmab (6 mg/kg)/placebo (Arm 1), pmab/ril (6/10 mg/kg, Arm 2, and pmab/gan (6/12 mg/kg, Arm 3). Administration was Q2W until disease progression or intolerance. Patients were ≥18 yrs old, had ECOG PS 0/1, and had prior irinotecan and/or oxaliplatin. The primary endpoint was objective response rate (ORR). The primary analysis of ORR used a Bayesian method. Secondary endpoints included progression-free survival (PFS) and safety. Biomarker analyses including c-Met expression by immunohistochemistry on archival tumor samples were completed.
Results: Of the 142 patients enrolled, 58% were men, mean age was 59.7 yrs, and ECOG PS of 0/1 was 40%/59%, respectively. The ORRs were 21%, 31%, and 22% and the median PFS (95% CI) were 3.7 (2.5-5.3), 5.2 (3.6-5.4), and 5.3 (2.7-5.7) months for Arms 1, 2, and 3, respectively. The posterior probability of OR >1 relative to Arm 1 for ORR were 0.93 for pmab/ril and 0.63 for pmab/gan. The most common adverse event of grade ≥ 3 in the pmab/ril arm was rash, and in the pmab/gan arm was hypomagnesemia. Immunohistochemistry results were obtained for 94% of the patients (134/142).
Conclusions: Pmab/ril met the prespecified criterion for improvement in ORR (greater than Arm 1). Pmab/gan was indeterminate. Pmab in combination with ril or gan was well tolerated. There were no strong correlations demonstrated between the expression of tumor c-MET protein and clinical outcomes. (© 2012 Amgen Inc.)