0000000000309764
AUTHOR
Robert A. Beckman
A randomized, double-blind, placebo-controlled phase 2 study of tigatuzumab (CS-1008) in combination with carboplatin/paclitaxel in patients with chemotherapy-naïve metastatic/unresectable non-small cell lung cancer
Abstract Introduction Tigatuzumab, a humanized monoclonal DR5 agonist antibody induces apoptosis in human cancer cell lines. The objective of this study was to investigate the antitumor effects of tigatuzumab combined with carboplatin/paclitaxel in chemotherapy-naive patients with metastatic/unresectable non-small cell lung cancer (NSCLC). Methods Patients with histologically or cytologically confirmed NSCLC stage IIIB/IV disease by RECIST (version 1.0) and ECOG-PS 0–1 were enrolled at 15 European sites. Patients received tigatuzumab or placebo intravenously with carboplatin/paclitaxel every 3 weeks (1 cycle) for up to 6 cycles. The primary end point was progression-free survival (PFS). Sec…
A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors.
Abstract Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose. Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis…