Rat IgG1 kappa Isotype Control [Cy5®]

Background: Ficlatuzumab, a humanised hepatocyte growth factor (HGF) IgG1 kappa inhibitory monoclonal antibody, was evaluated for recommended phase II dose (RP2D), safety, pharmacokinetics (PKs), antidrug antibody (ADA), pharmacodynamics (PDs) and antitumour activity as monotherapy or combined with erlotinib. Methods: Patients with solid tumours received ficlatuzumab 2, 5, 10 or 20 mg kg(-1) intravenously every 2 weeks (q2w). Additional patients were treated at the RP2D erlotinib. Results: Forty-one patients enrolled at doses <= 20 mg kg(-1). Common adverse events (AEs) included peripheral oedema, fatigue and nausea. Three patients experienced grade >= 3 treatment-related hyperkalaemia/hypokalaemia, diarrhoea or fatigue. Best overall response (44%) was stable disease (SD); median duration was 5.5 months (0.4-18.7 months). One patient has been on therapy with SD for 44 years. Pharmacokinetics of ficlatuzumab showed low clearance (0.17-0.26 ml h(-1) kg(-1)), a half-life of 6.8-9.4 days and dose-proportional exposure. Ficlatuzumab/erlotinib had no impact on the PK of either agent. No ADAs were detected. Ficlatuzumab increased serum HGF levels. Conclusions: Recommended phase II dose is 20 mg kg(-1) q2w for ficlatuzumab monotherapy or with erlotinib. Preliminary antitumour activity and manageable AEs were observed. Pharmacokinetics were dose-proportional and consistent with other IgG therapeutics. Ficlatuzumab was not immunogenic, and serum HGF was a potential PD marker.

Purpose: KW-2871 (IgG1 kappa chimeric antibody) targets GD3, which is upregulated in melanomas. We conducted a phase I trial of KW-2871 in patients with metastatic melanoma. Methods: Seventeen (17) patients were enrolled and received an initial test dose (10 mg/m(2)) intravenously. Two (2) weeks later, patients were stratified into 4 cohorts to receive 4 doses of KW-2871 (infused over 1 hour) at 2-week intervals (20, 40, 60, and 80 mg/m(2)). No premedications were administered for the test or first therapeutic doses. Results: Dose-limiting toxicities were Grade 3 laryngospasm and chest tightness with the initial therapeutic infusion at doses of 80 and 60 mg/m(2). The maximum tolerated dose (MTD) was established at 40 mg/m(2) of KW2871. The most common side-effect was urticaria (Grades 1-3) in 16 of 16 patients during an initial therapeutic infusion without premedication. The mean terminal half-life, clearance, and area under the concentration-time curve (AUC(0-t)) at a dose of 40 mg/m(2) for course I were 146 +/- 31 hours, 28 +/- 6 ml/hour, and 1922 +/- 491 mcg*hour/mL, respectively. Anti-human chimeric antibody was not detected. Two (2) patients in the 40 mg/m(2) cohort had stable disease. Conclusions: An MTD of 40 mg/m(2) without premedication was established for KW-2871, with urticaria being the most common side-effect and dose-limiting anaphylactoid infusion reactions.